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P1 Fall 2023 > pharmaceutics exam 1 > Flashcards

pharmaceutics exam 1 Flashcards

1
Q

what is pharmacy

A

the science, art, and practice of preparing, preserving, compounding, and dispensing medicinal drugs and of giving instructions for their use”

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2
Q

pharmacy as a
place
profession
business

A

A Place: Licensed pharmacists receive prescriptions to dispense medicines

  • A Profession:
    – Study and training,
    – Associations (many pharmacy organizations)
  • A Business: Pharmacists can own their own pharmacy – business people
    – practitioners
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3
Q

Pharmacy Heritage
instinct
awareness of drug effects on the person
What shaped early pharmacy/medicine

A

Our instinct to survive served an important purpose in early pharmacy
* There was evidence of drug use long before the formal documentation of use, they found that…
* Cool water alleviated pain
* Leaves from plants were used to treat infected skin areas
* Mud was used to close and heal wounds etc…

  • What shaped early pharmacy/medicine was the trial and error approach = Drug therapy
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4
Q

According to early history, why did people become sick?
what was their view on the mood of God?
what made someone healthy

A

The cause of disease was usually not biologically-based, due to environmental exposure or hereditary links.
The main reason was believed to be due to Evil Spirits.
* “In the land of the blind the one eye man is king”
– The man or woman with the most knowledge of how plants could be used to make remedies was usually consulted

  • Drugs alone were not sufficient to treat sickness
  • Compassion of a god
  • Observance of ceremonies
  • Absence of evil spirits (drive it out of your body) (made someone healthy)
  • Healing intent of the dispenser
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5
Q

The Tribal Apothecaries (person who prepared and sold meds.)
failures
successes

A

Failures:
-Inactive agents
-Underdosing
-Overdosing
-Poisoning

Successes
-Coincidence
-Inconsequential effect of drug
-Placebo effect (psychologic- non-therapeutic effect)

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6
Q

Early Research on plants for drugs

A

Their scientific knowledge increased over
time, and so did the application to the pharmacy
* Scientists began conducting research
* Karl Wilhelm Scheele (1742-1786)
-isolated morphine from opium

Friedrich Serturner (1783-1841)
* Joseph Caventou- (1795-1877)
* Joseph Pelletier- (1788-1842)
* Combined their talents

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7
Q

what was made to ensure drug Standards and Quality

what is USP/NF?

was it written vaguely?

what did books like USP and NF adopt, reflect, provide and demonstrate

A

Need for uniform standards to ensure quality
* Therefore, Pharmacopeia’s or Formularies were created. These are organized sets of monographs or books of standards.

  • Written with a high degree of clarity and specificity
  • USP* and NF – First one in 1820*
    – Adopt standards for drugs, pharmaceutical ingredients, and dosage forms
    – Reflect on the best current practices of medicine
    – Provides information on tests and assay procedures for
  • Demonstrating compliance with these standards – For individual components, not combinations
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8
Q

Drug Regulation & Control

the Food and Drug Act of 1906 was the first federal law to do what

the manufacturer’s claims of therapeutic benefit in 1912 said what about false claims and declared what about products

A

Food and Drug Act of 1906:
Was the very first Federal Law in the U.S. that required that “drugs marketed interstate comply with claimed standards for strength, purity and quality”.

  • Manufacturer’s claims of therapeutic benefit in 1912.
  • In this case, the Sherley Amendment said,
    » No More False Claims
    » Declared Products Misbranded
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9
Q

The Federal Food, Drug, and Cosmetic Act of 1938

what tragedy preceded this act

Why did 105 people lose their lives?

what was the excipient that was used?

what is the excipient used for today?

how did the FDA remove this drug from the market

A

There is a need for safe administration of drugs after a tragedy caused by Sulfanilamide a “wonder drug”.

  • toxicity: diethylene glycol
  • The drug was manufactured as an elixer, and diethylene glycol was used as the solvent to prepare the elixir
  • What is this drug used for today???- antifreeze for car

because they weren’t able to ban unsafe drugs at the time, the FDA removed/banned it based on a technecality that elixirs need to be prepared with alcohol and it did not have alcohol so it was banned

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10
Q

The FDCA of 1938 required all new drugs to be tested by whom for what

where did these tests have to be submitted and via what

what did this act mandate for drugs to be labeled with

what did this act authorize the FDA to do

A

– Required that all new drugs be tested by their manufacturers for safety.

  • Required that those tests be submitted to the government for marketing approval via the NDA (newdrug application)
  • Mandated that drugs be labeled with adequate directions

– Authorized FDA to conduct unannounced inspection

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11
Q

Federal Food, Drug, and Cosmetic Act of 1938

  • before a drug was distributed what needed to be filed and who needed to be approved

-did the FDA require drugs to be effective

A
  • No new drug could be distributed without the prior filing of a new drug application (NDA), and approval of the FDA.
  • The FDA now dealt with safe use of drug substances, but did not require that the drugs be (efficacious) effective in the treatment of disease
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12
Q

The FDA was given the job to
grant or deny products entering the market
based on
P
M
S
P
P
T
C
did they require drugs to effective?

A

– Product’s ingredients
– Methods used to evaluate products
– Standards used to evaluate formulations
– Preclinical studies
Pharmacology
Toxicology
– Clinical trials
Still, the FDA did not require drugs to be efficacious

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13
Q

Thalidomide Tragedy

who was thalidomide prescribed to

what did thalidomide cause

A

– Introduced on to the market October 1,1957 in West Germany

– Prescribed to pregnant women with morning sickness

– “Thalidomide” babies resulted all around the world

  • caused Phocomelia
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14
Q

What was the conclusion of the thalidomide tragedy/what did we need to strengthen

A

Thalidomide could have passsed our current drug laws
There is no question that we need to strengthen our food and drug regulations to include routine testing of new compounds pregnant animals

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15
Q

What medical condition did thalidomide cause

A

Phocomelia

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16
Q

What was the Kefauver-Harris amendments of 1962

A
  • The thalidomide tragedy was the main reason behind the development of this act
  • This amendment required manufacturers to prove a drug to be both safe and productive before granting FDA approval for marketing.

-Exempted from both safety and efficacy requirements were drugs that happened to enter the market between 1906 and 1938 aka ~ grandfather clause. Why? Drugs were never subjected to NDAs.

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17
Q

Drug classification on the basis of drug type

How are agents that are approved by the FDA categorized?

how is an agent that is safe to use without a provider categorized/classified

how is an agent that cannot be safely used without a provider categorized/classified

what is put on an agent that is not safe to use without a provider categorized/classified

A
  • Agents approved for marketing by the FDA are categorized according to the way that they may be obtained legally
  • For example,
    – If the drug is safe enough for a layman in treatment the agent is classified as “over the counter” (OTC)

– If the drug may be used only after expert diagnosis drug packaging must bear the symbol, “Rx-only” or bear the caution label

  • “Caution: Federal law prohibits dispensing without prescription”
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18
Q

*Durham-Humphrey Amendment of 1952

A

No refills (dispensing of drugs) without a valid prescription

  • This clarified the dispensing obligations of pharmacists
  • Defined drugs that cannot be used safely without proper medical supervision
  • Determined what drugs are OTC and what drugs are not
  • Refilling is necessary only if authorized in the prescription
  • Further supported by the Comprehensive Drug Abuse Prevention and control Act of 1970.
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19
Q

Comprehensive Drug Abuse Prevention and Control Act of 1970

what were drugs of abuse put under

what did this act establish

A

Drugs of abuse were put under a comprehensive regulatory framework

  • The act established 5 “schedules” for classification and control of drug substances, particularly those that were more likely to be abused
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20
Q

Schedule I, II, III, IV & V

A

The schedules provide decreasing levels of control from schedule I to schedule V.

  • Schedule I & II are high potential: ex.Heroin for schedule I
  • Schedule III is moderate potential: ex. Codein
  • Schedule IV&V is low potential: ex. Diazepam for schedule IV
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21
Q

FDA Pregnancy Categories
what are the 5 categories
what is the first category
what is the last category

A

1979- US FDA introduced the classification of fetal risks due to pharmaceutical agent use

  • What is the Risk vs. Benefit Ratio?
    – Category A: Studies failed to demonstrate a risk to the fetus (1st trimester- no evidence of risk in a later trimester)
    – Category B
    – Category C
    – Category D
    – Category X: Animal studies or humans demonstrated fetal abnormalities. Women outweigh potential benefits
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22
Q

“Black Box” Warnings

what is the FDA’s strongest labeling requirement used for

what does the FDA’s strongest labeling requirement emphasize when using the medication?

when is the FDA’s strongest labeling requirement used concerning adverse rxn and benefits?

when the FDA approves the drug does it still use FDA’s strongest labeling requirement? if so when

can local/state laws weaken FDA laws

A

FDA’s absolute strongest labeling requirements are used for the highest-risk medications.

– It emphasizes the importance of close patient monitoring when using the medications.

– Used when an adverse reaction is so serious in proportion to the potential benefit

– FDA approves the drug but restrictions to/when prescribing and distributing to ensure safety

– Local and State Laws may only strengthen FDA laws, never weaken them.

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23
Q

Drug Listing Act of 1972

what must each firm that manufactures or repackages drugs do with the FDA and submit for listing

what is an NDC & what does it stand for

how long is an NDC

A

“Each firm that manufactures or repackages drugs for the ultimate sale or distribution to patients or consumers must register with the FDA and submit appropriate information for listing”

  • National Drug Code (NDC) permanent registration code to identify manufacturer or distributor.
  • The code is 10 (or 11) digits long
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24
Q

National Drug Code (NDC)

– Example of NDC: NDC 00081-5421-12

what are the first 4 digits?

what are the next 3-4 digits?

what are the last 2 digits?

what is the correct format for NDC numbers

A

“Labeler code” “Product code” “Package code”
– How is one different from the other?

– Labeler code: Manufacturer/ distributor (1st 4 digits)
– Product code: Used to identify drug formulation (3-4)
– Package Code: Used to identify package size & type (3-2)

5-4-2 format!

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25
Q

what do
NDC 0081-5421-12 Represent
NDC 0057-346-421Represent

A

NDC 0081-5421-12
* Represents 4-2 digit product-code-package-
code configuration

NDC 0057-346-421
* Represents 3-3 digit product-code-package-code- code configuration

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26
Q

Abbreviated New Drug Application (ANDA)
The Drug Price Competition and Patent Terms Restoration Act of 1984 said that..

A

“Any originally approved new drug can be filed through an ANDA and bypass animal and human study testing.”

This reduced the time and money to market the generic version of a drug compound.

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27
Q

Prescription Drug Marketing Act of 1987
- prohibited what for drugs (RSTP)
-What did this decrease entering the legitimate market

Revisited and updated

Prescription Drug User Fee Act of 1992.
- what did it allow the FDA to do concerning drug and biological companies in addition to reviewing new drug and biologic applications within time frames

A

1987 Law- Prohibited the reimportation of drugs, and prohibits sales, trading, and purchasing of drugs. It decreased the risk of misbranded, repackaged, or mislabeled drugs entering the legitimate market

1992 Law- Prescription Drug User Fee Act of 1992. Allowed the FDA to accept user fees from drug and biologic companies in return for committing to review new drug and biological applications within certain time frames.

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28
Q

Dietary Supplement Health & Education of 1994
Dietary supplement and nonprescription drug consumer protection Act of 2006

A
  • Due to growing interest in using dietary supplements*, Congress expressed the need to regulate all labeling claims.
  • Manufacturers had to state the following:
    – “This product is not intended to diagnose, treat, cure, or prevent any disease”
  • Influences on body structure and function okay
  • Ex; increasing blood circulation; lowering cholesterol
  • Statements must be “truthful and not misleading”
  • vitamins, minerals, amino acids, and botanicals
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29
Q

Dietary Supplement and Nonprescription Drug Consumer Protection Act of 2006

A

Enabled FDA to implement a policy of GMPs for dietary supplements similar to those in place for pharmaceutical products.

  • Dietary supplements are now manufactured according to quality standards.
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30
Q

FDA Modernization Act of 1997
Revisited and updated
FDA Amendment Act of 2007

A

Streamlined FDA policies
* To codify many of the agency’s new regulations
* Monitors for regulatory compliance
* Establishes product labeling requirements
* Directs product recalls
* Expanded patient access to investigational treatment for serious life-threatening diseases
* Accelerated approval of new drugs
* Pediatric use of investigational drugs made possible

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31
Q

Drug Product recall

what are the 3 classes of recall

A

[FDA or manufacturer reveals that product presents a threat to the public]

  • Class I: Exposure will cause serious adverse health consequences or even death
  • Class II: Exposure will cause temporary or medically reversible adverse health consequences
  • Class III: Exposure is not likely to result in adverse health consequences
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32
Q

Code of Ethics

A

Conduct work in a professional manner- high principles are essential

  • No scientific misconduct tolerated
  • Recognize and respect differences in opinion in the interpretation of scientific data
  • Disclose sources of external conflicts
  • Report results honestly and accurately
  • Respect ownership rights of others and seek prior written approval from owner before disclosure
  • Do not discriminate on the basis of race, gender, creed or national origin
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33
Q

Brief History of Drug Discovery & Development

Plant poisons
Where did morphine, quinine, digitalis and belladonna come from originally

A

1800 to 1820: Organic plant acids were extracted from plants by pharmacists in Germany, France, and Sweden

1883: Synthesis of antipyrine.
Important because done in a test tube and this changed the way drugs were discovered from this point forward

1925 to 1945: Rapid advances in pharmacy research.
Alexander Flemming discovered Penicillin
James-Watson Crick solved the structure of DNA

Morphine: from opium poppy

Quinine: from cinchona bark

Digitalis: from foxglove

Belladonna: from deadly night shade

The alkaloids are not present in plants to supply us with medicines but are probably present to discourage predators

Problem is with purity and producing enough for our needs

Not all plants of same species are grown under same conditions so potency will vary

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34
Q

what was the issue with getting our meds from plants

A

Problem is with purity and producing enough for our needs

Not all plants of same species are grown under same conditions so potency will vary

The alkaloids are not present in plants to supply us with medicines but are probably present to discourage predators

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35
Q

what drugs came from vinca rosea

A

Vinblastine and Vincristine

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36
Q

what did Vinblastine and Vincristine treat

A

Vinblastine- treat Hodgkin’s disease (a form of lymphoid cancer)

Vincristine-used clinically in the treatment of children’s leukaemia

and breast cancer (not sure actually)

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37
Q

what drugs came from Pacific yew (taxus brevifolia)

A

taxol
which is used today to treat breast cancer patients

the tree we get it from is about 100 yrs old and its content could treat 3 out of the 4 rounds of chemo

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38
Q

is it worth cutting all the Pacific yew (taxus brevifolia) trees down for medicinal use? so what did we do

A

No! so we made the synthetic form of the chemical in lab and also made isomers of it too

this even increases purity!

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39
Q

what is the propose of Drug Discovery

who is involved in this

A

To find active ingredients and/or modify the chemical structures of existing active ingredients of drugs to form the basis of a new agent.

Chemists
Pharmacologists
Toxicologists
Formulation developers (i.e. pharmaceutics

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40
Q

state what each one does

Chemists
Pharmacologists
Toxicologists
Formulation developers (i.e. pharmaceutics

A

Chemists: an expert in chemistry; a person engaged in chemical research or experiment

Pharmacologists: medical scientists working to develop new drugs. They may work in a lab, testing medications by studying tissue and cell samples. They may work in clinical trials, conducting research on voluntary patients.

Toxicologists: a scientist who has a strong understanding of many scientific disciplines, such as biology and chemistry, and typically works with chemicals and other substances to determine if they are toxic or harmful to humans and other living organisms or the environment.

Formulation developers (i.e. pharmaceutics) scientists must determine the most appropriate route to achieving effective drug delivery based on patient need, then optimize the formulation’s characteristics based on a knowledge of the drug product’s bioavailability and processing requirements.

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41
Q

what Is the purpose of drug development and what does it require and do they work

A

To provide superior dosage forms and a way of delivering effective drugs throughout the body
Mostly done by scientists usually with a PhD

At a pharmaceutical company
At a school of Pharmacy

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42
Q

Early Formulation Studies addresses what question

are early formulation studies completed before or after preclinical studies

A

What properties related to pharmaceutics are studied?

EARLY FORMULATION STUDIES ARE COMPLETED BEFORE PRECLINICAL STUDIES INVOLVING ANIMAL EXPERIMENTATION

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43
Q

what does each letter mean in the Early Formulation Studies/ What properties related to pharmaceutics are studied?

DPDPS

A

Drug solubility:
Less than 10 mg/ml is considered poorly soluble

Partition coefficient:
Preference for one phase (i.e., lipid) verses a second phase (aqueous).

Dissolution Rate:
Speed at which a drug substance dissolves in a medium

Physical Form:
Crystal verses amorphous verses powder etc.. Will alter the rate and extent of absorption

Stability:
Retention of drug substances within dosage forms
Temperature and relative humidity (RH) effects

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44
Q

What is The “Goal Drug”

A

Ideally this group seeks to develop a compound with the following characteristics

Can produce a desired effect

Can be administered at the most desirable route (orally)

Can be administered at a minimal dosage and frequency

After exerting a necessary effect should be eliminated from the body efficiently without side effects

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45
Q

A “Lead Compound”

A

This compound is the closest agent to the “goal drug”, possessing the fundamental desired biologic or pharmacologic activity

It may NOT contain all of the properties of the desired compound, and so medicinal chemists often modify the lead compound

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46
Q

what does a Drug Researcher have to know

A

Pharmacology

Drug Metabolism

Toxicology

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47
Q

explain Pharmacology, Drug Metabolism, toxicology
that a drug researcher has to know

What is the purpose of CDER?

How does the CDER balance the benefit vs. known risks ?

A

Pharmacology: Determines biologic activity and mechanism of drug action in vitro & In vivo

Drug Metabolism: Determines the absorption, distribution, metabolism and elimination (ADME)
What is the extent of drug absorption and distribution in the body?
What is the mechanism of the drug metabolized by the body?

Toxicology: Deals with adverse and undesirable effects of the drug. Consider: What is the maximum tolerated dose? What is the lethal dose?

purpose of CDER - Assess benefit to risk relationship
- Is a particular drug safe and effective enough?

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48
Q

Other examples of issues addressed by researchers in vivo

A

Make sure that the appropriate dosage form is being used to deliver therapeutics to the intended site of drug action

Non-specific delivery to intended targets is the main reason for drug-related side-effects

ex: used a mouse to see the angiogenesis of a tumor

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49
Q

what does the CDER do

Other examples of issues addressed by researchers in vivo

A

Assess benefit to risk relationship:
- Is a particular drug safe and effective enough?
- AZT (azidothymidine) toxic but highly effective

Make drugs available to the public sooner

Provide clear standards for drug evaluation

High priority drugs– These are defined as drugs that offer a significant medical advantage over current therapies

Cancer drugs–Division of Oncology

Contraceptive drug & urologic drug products–Division of reproductive & Urologic drug products

Generic drugs– Division of Generic drugs

Make sure that the appropriate dosage form is being used to deliver therapeutics to the intended site of drug action

Non-specific delivery to intended targets is the main reason for drug-related side-effects

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50
Q

Investigational New Drug (IND) Application

A

Once a drug has been developed, before it can be tested in humans, it must be filed with the FDA. This is an IND Application.

Application protects the rights & safety of subjects and makes certain that the research objectives stated in the investigational plan can be achieved.

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51
Q

What is the main purpose of the IND application?

what happens after IND application

A

to provide the FDA with sufficient information to make a meaningful evaluation of a new drug

IND is next assigned to a CDER official,
- Officials can place hold on trial due to inadequate information, inadequate qualifications of investigators or potential harmful risk to patients

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52
Q

IND Application
What Is the goal of phase I clinical trials

A

Preclinical studies demonstrate adequate safety. This is to be determined by Phase I clinical trials.

Phase I Clinical Trials

Drug should show promise as a useful drug
- Phase I: What is the safe dose in 20 to100 patients)?
- Usually brief study (less than 1 year).
- Purpose is to determine toxicology, metabolism, and pharmacologic actions

Application contains:
- The plan for the study
- Chemical Structure
- Animal testing results
- Manufacturing information

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53
Q

phase I clinical trial
has how many people

for how long

what question does it want to answer

how is drug used

where is it done

A

Phase I: What is the safe dose in 20 to100 patients)?
Usually brief study (less than 1 year).
Purpose is to determine toxicology, metabolism, and pharmacologic actions

Application contains:
The plan for the study
Chemical Structure
Animal testing results
Manufacturing information

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54
Q

What about clinical trial material (CTM) for Phase I studies?

A

Biopharmaceutical properties –> clinical study

Practical considerations
–Actual supply of bulk
–Time allowed for preparing bulk stock

Advantages of extemporaneous formulations
–Short development time
–Minimal drug substance requirements (few hundred grams)
–Minimal formulation development
–Minimal analytical work

Disadvantages of extemporaneous formulations
–Unpleasant taste
–Patient compliance issue
–Dosing inconvenience for
–multiple dose studies

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55
Q

Phase II clinical trials
has how many people

for how long

what question does it want to answer

how is drug used

where is it done purpose

A

To determine compound’s effectiveness

Drug is tested in hundreds of patients (~100 to 300 people).

Patients have the disease that the drug is intended to treat

Extensive pharmacologic, toxicological and pharmacological testing

Many clinical agents do not make it to this point cause they prove to be unsafe

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56
Q

What about clinical trial material (CTM) for Phase II studies?

A

“powder in a bottle”- not very good approach

Capsules or tablets are typically necessary

Generally, same dosage form as phase I can be used here.

Except, When required dosage strength is not supported & When medium-to-large scale is not feasible

Alternatively, a new formulation closer to desired commercial dosage form can be introduced during Phase II

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57
Q

What about (CTM) for Phase II studies?-Continued-

A

Other Critical factors:
- Phase II covers a large dose range so # of dose strengths may be large

  • This is determined by,
    Team of scientists (pharmaceutical scientists, pharmacokineticists, & clinical study and clinical supply coordinators)

Limitations with high dose strengths:
–Dissolution and processability

Limitations with low dose strengths:
–Content uniformity and stability issues

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58
Q

Phase III clinical trials purpose

A

To demonstrate long-term safety & efficacy of drug product; to discover drug’s efficacy standards

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59
Q

phase III clinical trials

has how many people

for how long

what question does it want to answer

how is drug used

where is it done

A

Several thousands of patients in many centers (~1000-3000 people)
Carried out over several years
How good is the drug in treating the disease or condition?

What are the short-term side effects and risks associated with drug use in patients whose health is impaired?

Investigational drug will be used in several randomized, controlled studies in various clinical research facilities including,

Clinical research facilities
Veterans administration
University teaching hospitals

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60
Q

What about clinical trial material (CTM) for Phase III studies?

A

Data from stability should be performed on at least 3 primary batches of drug products

Stability testing must cover minimum period of12 months typically at 25 ºC

Changes in dosage strengths and manufacturability of CTM may be necessary to achieve specific goals of Phase III

However, the same formulation, processing and packaging procedures as with commercial product is recommended

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61
Q

in phase I, II, III, what is the % of drugs that are successfully tested

A

phase I: 70%

phase II: 33%

phase III: 25%-30%

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62
Q

Usual adult dose

A

Starting dose for a patient

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63
Q

Usual dosage range

A

Safety dose range for administering drug product

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64
Q

Dosage Regimen

A

Schedule of dosage

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65
Q

Maintenance doses

A

Maintain clinically relevant drug levels in blood

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66
Q

Prophylactic dose

A

Administered to prevent patients from contracting the disease

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67
Q

Therapeutic dose

A

Administered once disease has been contracted

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68
Q

Minimum effective concentration (MEC):

A

The minimum dose required to get a desired effect

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69
Q

Minimum toxic concentration (MTC):

A

Administering drugs above this level will produce dose related toxicities

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70
Q

Median effective dose (MED):

A

This dose will produce a desired intensity of a drug effect in 50% of the individuals tested

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71
Q

Time-blood level curve

A

Ideally, the drug serum levels should be maintained above the MEC and below the MTC.

Concentrations above the MTC will cause toxic side effects

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72
Q

Age

A

Neonatal, Pediatric & Geriatric Patients

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73
Q

Body Weight

A

Milligrams (of drug)/ per kilogram of body weight

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74
Q

Body Surface Area

A

1 mg/M2 BSA- NOMOGRAM

found using a nomogram

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75
Q

Sex

A

Men and Women have different responses to certain drugs due to biochemical & Physiologic factors

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76
Q

Pathologic State

A

Disease State

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77
Q

Times of administration

A

: Before or after meals

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78
Q

Tolerance

A

Ability to endure influence of a drug

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79
Q

BSA is used to determine drug dose in humans

A

Due to the correlation that exists between physiological processes and body surface area (BSA), some drug doses are determined based on this relationship

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80
Q

An adult measuring 67 inches in height and weighing 132 pounds would have a BSA of approximately how many square meters?

A

1.7

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81
Q

Batch

A

a specific quantity of a drug of uniform specified quality produced according to a single manufacturing order during the same cycle of manufacture

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82
Q

Batch wise control

A

the use of validated in-process sampling and testing methods in such a way that results prove that the process has done what it purports to do for the specific batch

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83
Q

Certification

A

documented testimony by qualified authorities that a system qualifications, calibration, validation or revalidation has been performed appropriately and that the results are acceptable

84
Q

Compliance

A

determination through inspection of the extent to which a manufacturer is acting in accordance with prescribed regulations, standards, and practices

85
Q

Component

A

any ingredient used in the manufacture of a drug product, including those that may be present in the finished product

86
Q

Drug Product

A

a finished form that contains an active drug and active ingredients. the term may also include a form that does not contain an active ingredient

87
Q

Active Ingredient or active pharmaceutical ingredient (API)

A

any component that is intended to furnish pharmacologic activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or function of the body of man or other animals.

88
Q

Inactive ingredient

A

Any component other than the active ingredients in a drug product.

89
Q

Lot

A

: A batch or any portion of a batch having uniform specified quality and a distinctive identifying lot number.

90
Q

Lot number, control number, or batch number:

A

Any distinctive combination of letters, numbers, or symbols from which the complete history of the manufacture, processing, packaging, holding, and distribution of a batch or lot of a drug product may be determined.

91
Q

Master record

A

Record containing the formulation, specifications, manufacturing procedures, quality assurance requirements, and labeling of a finished product.

92
Q

Quality assurance

A

Provision to all concerned the evidence needed to establish confidence that the activities relating to quality are being performed adequately.

93
Q

Quality audit

A

A documented activity performed in accordance with established procedures on a planned and periodic basis to verify compliance with the procedures to ensure quality.

94
Q

Quality control

A

The regulatory process through which industry measures actual quality performance, compares it with standards, and acts on the difference.

95
Q

Quality control unit

A

An organizational element designated by a firm to be responsible for the duties relating to quality control.

96
Q

Quarantine

A

An area that is marked, desig- nated, or set aside for the holding of incoming components prior to acceptance testing and qualification for use.

97
Q

Representative sample

A

A sample that accurately portrays the whole.

98
Q

Reprocessing

A

The activity whereby the finished product or any of its components is recycled through all or part of the manufacturing process.

99
Q

Strength

A

The concentration of the drug substance per unit dose or volume.

100
Q

Verified

A

Signed by a second individual or recorded by automated equipment.

101
Q

Validation

A

Documented evidence that a system (e.g., equipment, software, controls) does what it purports to do.

102
Q

who establishes regulations under the standards for good cGMPS

what is the purpose of establishing regulations/what do they have to do with quality?

what act inspired the first set of GMP

Who is the established requirements for, and does it apply to domestic or foreign suppliers who sell most of their product in the U.S., What can the people who established this do concerning inspections

is there a distinction in the way that the regulations are applied

A

Regulations are established by the FDA

Purpose: to set minimum standards for product quality

Kefauver-Harris Act inspired the first set of GMP regulations

Established requirements for all aspects of pharmaceutical manufacture

Applied to domestic and foreign suppliers with bulk components and finished products sold in the US.

Unannounced FDA inspections applied here as well

No distinction in how regulations are applied to domestic and foreign suppliers and manufacturers

103
Q

what should you know about cGMP for Finished Pharmaceuticals?
O P

B F

E

L C

R R

you should know the P, L, S&T of pharmaceuticals

A

Organization and personnel

Buildings and Facilities

Equipment

Laboratory Controls

Records and Reports

Packaging, Labeling, Storage, and Transportation of Pharmaceuticals

104
Q

The regulatory process through which the industry measures quality performance, and compares with standards and acts on the difference?

Quality assurance
Quality audit
Quality control
Quality control unit

A

Quality control

105
Q

what are the organization and personnel responsible for

what is this division responsible for in terms of education and training, product components, product specifications, finished product standards for packaging and labeling

what should any supervisor have to oversee the task?

A

Quality control, employees, consultants

Responsibilities are:
Adequate education and training

Assess product components and reject if necessary

Assess product specifications, finished products, standards of packaging and labeling

Any supervisory personnel must have adequate training and qualifications to oversee the task

106
Q

buildings and facilities
what do they deal with in terms of design, features, and functional aspects

They ensure that their design enables thorough what and effective use of what

what physical things do they deal with
W
S
L
M
W M
S A
F S A
S A Q P & H A F R C

Afterward, who must be logged in, inspected, and signed off on

A

Deals with design, features, and functional aspects of buildings and facilities

Must be designed to enable thorough cleaning, inspection, safe & effective use for performance operations and evaluations

Water quality standards

Security

Lighting

Materials used for floors, walls, ceilings

Weighing and measuring rooms

Sterile areas

Flammable storage areas

Storage areas for quarantine purposes, and holding areas for rejected components

Everything must be logged in, inspected by a supervisor, and signed off

107
Q

equipment
what is it exactly to

this goes for the equipment’s
T
L
R C
P O E must not interfere with the D O D P
F M M N M with I D P. This must be prevented

A

Exact to the specifications

Type

location

Routine calibration

Parts of equipment must not interfere with the development of drug products

Filter materials must not mix with injectable drug products. This must be prevented.

108
Q

for Control of components, containers, and closures
Written procedures must be _____ and ______

Bulk chemical ingredients ______ must meet __________ at time _________

When ingredients are received ________

what must be logged in for ingredients that just came

logged in for ingredients:
Purchase ______
D of R
Suppliers______: stays with _________________________________
Q R

What happens to raw materials

what happens to materials not meeting specifications

A

Written procedures must be developed and followed

Bulk chemical ingredients of drug products must meet all specifications at the time of ordering

When ingredients are received they must be officially logged in.

When ingredients are received they must be officially logged in

logged in for ingredients:
Purchase order number
Date of receipt
Suppliers Stock or Control number: stays with the product and follows it all the way through development
Quantity received

Raw materials are quarantined, and quality verified.
Materials not meeting specifications are rejected

109
Q

Production and process controls
Written documentation is required to make sure that each drug product has the correct: I, S, Q & P

All automated equipment is what

what is done to batches on a regular interval to check for what—who performs this

A

Written documentation is required to make sure that each drug product has the

Correct Identity
Correct Strength
Correct Quality
Correct Purity

All automated equipment is evaluated
Batches are evaluated at regular intervals to check on batch-batch consistency

Production personnel
Quality control laboratory

110
Q

Packaging and Labeling Control
Written documentation is required for R, S, H, S, and T of products

what happens to outdated labels

what happens when drugs need further investigation by quality control

what happens when drug products are approved by quality control operations and what does it prevent

A

Written documentation is required for
Receipt, storage, handling, sampling and testing of products

All outdated labels must be destroyed, it must be destroyed

When drug products need further investigation by the quality control unit the problems must be identified and resolved

When drug products are approved by quality control operations, visual and/or electronic inspection is performed–This prevents mislabeling of products
Check for expiration date, product batch, or lot #
Tamper-evident packaging required

111
Q

Records and Reports
Production information must be ______ for at least ______ following______ batch

Control records must include the list below, and must be made available to the FDA officials at the time of inspection.
N S of product dosage form
C & D units
Control ________
E used
_______controls
R of _______
C of instruments

A

Production information must be maintained on file for at least 1 year following expiration date of batch

Control records must include the list below, and must be made available to the FDA officials at the time of inspection.

Name and Strength of product dosage form
Components and dosage units
Control procedures
Equipment used
In-process controls
Results of analysis
Calibration of instruments

112
Q

Returned and Salvaged Drug Products
must be identified by _____ and _____ quality

What do you do when products come back from the marketplace? may be ______ or ______

if the product was not stored under appropriate conditions, can it be on the marketplace again

what must be documented and dated

A

Must be identified by lot# and product quality

What do you do when products come back from the marketplace?
—If the products happen to meet all product specifications they may be used again. The product may be “Salvaged or Reprocessed.”

If the products have not been stored under appropriate conditions the products should never see the marketplace again

The exact reason for product return must be documented and dated.

113
Q

Additional cGMP Regulatory Requirements
Pharmaceutical excipients must be ______ to _______ specifications.

is there an FDA approval system for pharm. excipients

A

Pharmaceutical excipients must be produced according to cGMP specifications.

NO FDA APPROVAL SYSTEM FOR PHARMACEUTICAL EXCIPIENTS

114
Q

Clinical Trial Materials
CTM in ________ investigations must be ________ to _____________ regulations

Pharmaceutical __________ are ____________ and optimized for human_______ from phase ___ to ________.

All regulatory requirements must be __________ and reported to ____________

For example, the production of 100,000 capsules
Placebos and/or comparator products must be prepared by this stage

A

CTM in clinical investigations must be produced according to cGMP regulations

Pharmaceutical products are continuously characterized and optimized for human treatment from phase I to phase II.

All regulatory requirements must be met by phase III and reported to the FDA

For i.e., production of 100,000 capsules
Placebos and/or comparator products must be prepared by this stage

115
Q

Current Good Compounding Practices
Patient-specific medications, why?

Dosages are not_____ ____

_____ _______forms are not available

Patients are _______ to certain _______ or cannot take due to ___________

Children have __________

Some medicines _________ dispensing

____________ not yet available by the manufacturer

Physicians have _____________

Veterinary products not always ________

Home health care __________ :__________

Hospice care: _________ to pain management

A

Dosages are not commercially available

Certain dosage forms are not available

Patients are allergic to certain excipients or cannot take due to religious reasons

Children have different needs

Some medicines require frequent dispensing

Some medicines not yet available by manufacturer
Physicians have different needs

Veterinary products not always available

Home health care pharmacies: Sterile preparations

Hospice care: new approaches to pain management

116
Q

Packaging, Labeling, and Storage of Pharmaceuticals
Containers:
Must meet what

Specifications vary according to container type, I.e.,
Parenterals and non-parenteral

_________

________, _________ and metal

A

Containers:
Must meet specifications for clinical trials

Specifications vary according to container type,
I.e:

Parenterals and non-parenterals

Pressurized

Glass, plastic and metal

117
Q

Plastic vs. Glass containers
how do plastic containers have that glass do not
L
R to I
G F
P S B
U D D

Autoclavable Plastic:
PVC is produced when

A

Plastic containers have an advantage over glass containers:
Lightness in terms of weight
Resistance to impact
Greater flexibility in terms of design and appearance
Plastic squeeze bottles (for ophthalmics, nasal sprays, lotions)
Unit-dose dispensing (ie., in healthcare institutions)

autoclavable plastic:
Polyvinyl chloride (PVC) is produced if a chloride atom is added to every other carbon atom in a polyethylene polymer.
PVC is a strong and rigid material useful for packaging capsules and tablets, but can not be sterilized by gamma radiation.
Newer plastics such as polyethylene terephthalate (PET) which can be sterilized by gamma radiation?

118
Q

What are the problems with plastic containers over glass?
Permeability of ________
—-Atmospheric _____________

_________ of constituents of container to _________ contents
—-Such as ________ additives

Absorption of _________ from contents to ________

Transmission of ________ through container

Change in ________ material _________

A

Permeability of containers
——-Atmospheric oxygen, moisture vapors

Leaching of constituents of container to internal contents
——-Such as polymer additives

Absorption of drug from contents to container

Transmission of light through container

Change in container material over time

119
Q

what is the purpose of Child-resistant and Adult-senior-use packaging?

what makes a container child-resistant/what age is the threshold for child resistance

what designs are used to prevent children from opening containers:
_______arrows,
press _______ and _______
________ and turn
Latch _______

why are some drugs exempt from this

A

To prevent accidental poisoning

The child-resistant container is one that is difficult to open for children under 5 years of age

Designs used to prevent children from opening containers are:
Align arrows
press down and turn
Squeeze and turn
Latch top

Certain drugs are exempt due to practical considerations, sublingual tablets, and cardiac drugs due to immediate access.

120
Q

what makes up Compliance Packaging
__________
Prescription ________
_________ Labeling
________

A

Labeling
Prescription Label
OTC Labeling
Storage

121
Q

what must the label meet?

what does labeling include: ________ container, packaging, ______ , company ________ , brochures, and any ________-

where must the benefit to risk factors be indicated?

what is put on prescription labels to reduce medication errors and what does it assure pharmacists that the prescribed drug is appropriate

A

Must meet the Code of Federal Regulations

Labeling includes immediate containers, packaging, inserts, company literature, brochures, and any mailings

The benefit to risk factors must be indicated in the packaging inserts…..

To reduce medication errors, there is thought to include “indication” on prescription labels to help pharmacists ensure that the prescribed drug is appropriate

122
Q

what must a pharmacist include on the dispensed medication
Name and _______ of ________
______ number of the ________
Date of ________ (or date of its filling/refilling)
________ of the _______
Name of __________
Directions for ________ (including any precautions as indicated on the prescription)

A

Name and address of pharmacy
Serial number of the prescription
Date of prescription (or date of its filling/refilling)
Name of the prescriber
Name of patient
Directions for use (including any precautions as indicated on the prescription)

123
Q

OTC Labeling in 1997

why did the FDA require it

what did the FDA say the label had to be organized into

what must it contain?

A

Due to inconsistent practices, the FDA developed a standard procedure for labeling OTC drug products

FDA called for simple headings and subheadings for easy understanding

OTC package labeling must contain warning statements if misuse can lead to serious complications

124
Q

OTC labeling: What is required on the label?

________ name

Net _______ of _______
–This includes all ingredients

Must indicate the _______ category

_______ and warnings to protect _______

_______ content (for oral products) when necessary if
5 mg or more per single ______
140 mg or more in ________ dose

Storage _________
—Must include storage in a safe place out of the reach of _______
—-_______ number and expiration ________

A

Product name

Net quantity of contents
This includes all ingredients

Must indicate the pharmacologic category

Cautions and warnings to protect consumer

Sodium content (for oral products) when necessary if
5 mg or more per single dose
140 mg or more in the maximum dose

Storage conditions
Must include storage in a safe place out of the reach of children
Lot number and expiration date

125
Q

what may OTC lead to

ex: what may a laxative cause

as a result, what does the warning label say

A

Medication may lead to serious complications

Ex: Laxatives may cause additional pain during appendicitis. For this reason,

“Warning: Do no use when abdominal pain, nausea, or vomiting is present. Frequent or prolonged use of this preparation may result in dependence on laxatives”

126
Q

what can medications mask requiring medical attention?

ex: how serious is a cough

what does the warning label say

A

Medications can mask serious conditions requiring medical attention

Ex: how serious is a cough?

“Warning: A persistent cough may be a sign of a serious condition. If cough persists for more than 1 week, tends to recur, or is accompanied by a fever, rash, or persistent headache, consult a doctor ”

127
Q

Dietary Supplement Labeling

Claims must be _________ and __________
No disease claims _______
For ex, those that infer “drug can be used to prevent, treat __________ a disease.”

A

Claims must be accurate and truthful

No disease claims allowed

For ex, those that infer “drug can be used to prevent, treat cure,
mitigate, or diagnose a disease.”

128
Q

Storage conditions and special considerations

what is the purpose of having storage conditions?
Freezer: ___ and _____
Cold: Does not exceed ____ (46 ºF)
Cool: Between ______ and ______
Room Temp: _____ to _____
Warm: Between ____ and ______
Excessive Heat: Above ______

A

To ensure the stability of pharmaceutical preparation

The following are conditions defined by USP
Freezer: -25 and -10 ºC
Cold: Does not exceed 8 ºC (46 ºF)
Cool: Between 8 ºC and 15 ºC
Room Temp: 20 ºC to 25 ºC
Warm: Between 30 ºC and 40 ºC
Excessive Heat: Above 40 ºC

Protection from Freezing
Protection from Light

You must maintain appropriate
conditions of temperature and
humidity during shipment.
Special consideration
may be needed

129
Q

Characteristics of the ideal dosage form

what should the final dosage form be
B
D & D form should be _______
F should be: S, E admin., S admin, Efficacious

A

Biocompatible

Drug and dosage forms should be compatible

Formulation should be
Stable
Easily administered
Safely administered
Efficacious

130
Q

Other reasons why we need dosage forms?
To ______protection from destructive _____ influences (atmospheric oxygen, humidity…)
To provide _______ from ______ pH
To address _________ taste or ________
To provide ________ preparations
To control the _______ of drug release
To _______ drug _____
To provide for ________ into body’s ______

A

To provide protection from destructive chemical influences (atmospheric oxygen, humidity…)
To provide protection from gastric pH
To address offensive taste or odors
To provide liquid preparations
To control the rate of drug release
To improve drug action
To provide for insertion into the body’s orifices

131
Q

General considerations
Match ______ form to the _______illness
Select dosage forms to ________ patient-_______needs
For children less than________ the ______dosage forms for oral route of administration are best
To assist the ______ with self-_______ procedures

A

Match dosage form to the appropriate illness

Select dosage forms to address patient-specific needs

For children less than 5 years of age the liquid dosage forms for oral route of administration is best

To assist the elderly with self-medication procedures

132
Q

Preformulation considerations
Physical ______
Microscopic ______
Melting ______depression
The ______rule
Particle ______
Polymorphism
______
Amorphous
_______
Solubility and ______size
Solubility and _____
Dissolution
Membrane _________
Diffusion
_______Law
Partition _______
Pharmaceutical _______ & Excipients
Reaction _____
Zero ______ reactions
First order _____

A

Physical Description
Microscopic examination
Melting point depression
The phase rule
Particle size
Polymorphism
Crystal
Amorphous
Solubility
Solubility and Particle size
Solubility and pH
Dissolution
Membrane Permeability
Diffusion
Ficks Law
Partition Coefficient
Pharmaceutical Ingredients & Excipients
Reaction rates
Zero-order reactions
First order reactions

133
Q

Physical Description
The majority of drugs are in _____form:
Crystalline or ______ constitution

Chemical properties:
Structure, _____ , and _______

Physical Properties:
Particle size, _______ structure, melting _______and solubility

Biologic Properties:
Ability to get to ______ of drug ______ and elicit a _______response

A

The majority of drugs are in solid form
Crystalline or amorphous constitution

Chemical properties:
Structure, form, and reactivity

Physical Properties:
Particle size, crystalline structure, melting point and solubility

Biologic Properties:
Ability to get to the site of drug action and elicit a biologic response

134
Q

Microscopic Examination
Is the appropriate site of
____ ______ targeted?

Gives indication of
particle _____ for finished
_______

Some ideas of _____
of ______ form

A

Is the appropriate site of
drug action targeted?

Gives indication of
particle size for finished
Pharmaceuticals

Some ideas of stability
of dosage form

Particles are sized directly and
individually, rather than grouped statistically

135
Q

Melting Point Depression

Low____ _____ drugs soften during a ______ step where _____ is generated

The melting point can be used to determine ______

DSC = Differential Scanning Calorimetry
Measures thermal phase ____, which can be used to determine the _____ of a given drug substance. How??

A

Low melting point drugs soften during a processing step where heat is generated

The melting point can be used to determine purity

DSC = Differential Scanning Calorimetry
Measures thermal phase behavior, which can be used to determine purity of a given drug substance. How??

Mp Pure A = 124 ºC
Mp Contaminated A (5% B) = 95-115 ºC

Used for determining:

Determination of purity
Solid drug + Solid pharmaceutics ingredients

136
Q

what is melting point depression used for

A

Determination of purity

Solid drug + Solid pharmaceutics ingredients

137
Q

Thermogram

what is a sample chamber

what is an experimental chamber

A

A plot of the energy absorbed as the temperature of the system is raised.

For e.g., the peak is caused by the absorption of energy required to melt the lipid bilayer

This is a thermogram for the melting of lipids used to prepare dosage forms.

Sample chamber:
Contains dosage form without the drug

Experimental chamber: Contains dosage form with drug

138
Q

Phase diagrams

what do they reveal about melting point

what are the phases

what happens is a substance is added to either one of these phases

what is the minimum melting point

A

A phase diagram (aka~ temperature-composition diagram) “reveals the melting point as a function of composition of two or
three component systems”

The phases are non-solid and solid

When a substance is added to either one of these phases (that is Pure A or Pure B), the melting temperature of the pure component(s) decrease.

Minimum melting point = EUTECTIC POINT

Each phase I, II, III, & IV is a
different part of the system
separated by boundaries

139
Q

Particle Size
what does particle size distribution effect

what are the types of Physical and chemical properties of drug substances

A

Physical and chemical properties of drug substances

Drug dissolution rate

Bioavailability

Content uniformity

Sedimentation

Textures

140
Q

Polymorphism
how much of it does it represent for all organic drug compounds

what are the Physicochemical properties of drug compounds

is more more energy required for a molecule to escape from a crystal or from a amorphous powder–what can we conclude

A

PolymorphismRepresents 1/3 rd of all organic drug compounds

Physicochemical properties of drug compounds
Non crystalline (or amorphous forms)
Crystalline (crystal structure)

“The energy required for a molecule of drug to escape from a crystal is much greater than the energy required to escape from an amorphous powder”

therefore

Amorphous form of drug is more soluble than the crystal form

141
Q

Polymorphism: examples’

which is more soluble, crystal form or amorphous form

A

amorphous form

142
Q

are antibiotic substances like novobiocin and chloramphenicol more soluble in crystal or amorphous form and what does that allow for GI tract absorption

which can be more active crystal or amorphous forms of drugs like penicillin G and thus what is made better

A

they are more soluble in amorphous form –Absorption from GI tract is rapid
in amorphous form

crystal form can be more active than amorphous form and thus Its crystal form results in a better therapeutic response

143
Q

what must a drug possess to be considered effect, can increase solubility

what determines solubility

what can you do to Make an excess amount of a drug dissolve and what can be determined from it

A

“Drug must possess some aqueous solubility to be considered effective”–insoluble compounds can lead to incomplete absorption. Solubility can be increased by chemical modification (ie., salt or ester form of a drug is a favorable chemical modification)

Solubility is determined by an ‘equilibrium solubility’ method.

Excess of drug is placed in a solvent and shaken at a constant temperature until an equilibrium is obtained.

This is done to determine the degree of solubility

144
Q

Solubility and pH
what is pH

what can be adjusted to enhance solubility

can all drugs benefit from the answer above

what can be used instead of the above option

A

The pH can be adjusted to enhance solubility.

Not all drugs can benefit from adjustments to pH. Why not?
“For example weak acids or basic drugs require significant changes in pH that are outside the physiological limits.

When manipulation of pH is not an option due to physiological issues the following can be used:
Co-solvents:
Micronization:
Dispersion:
Emulsion:

145
Q

Which of the following is used to improve flow properties of powder mixtures?

colloidal silica
acacia
bentonite

A

colloidal silica for tablet gliding!

acacia for emulsifying
bentonite for clarifying agent and suspending agent

146
Q

what is dissolution (drug, fluids, absorption site)

what is the rate limiting step in the absorption process

_____ goes up when _____ goes down

____ goes up when _____ goes up

what can dissolution time effect

A

is the time it takes for a drug to dissolve in fluids at the absorption site.

Dissolution is the rate limiting step in the absorption process

absorption rate will rise when particle size goes down

dissolution goes up when solubility goes up

dissolution time can influence duration of therapeutic effect

147
Q

what makes up a dissolution apparatus

A

motor
paddle
compact
solvent (could be HCl)

148
Q

Diffusion
what do most drugs under go and usually in what part of the cell

what is fick’s law of diffusion

A

Most drugs undergo transport by simple diffusion, whether in the cytoplasm or interstitial fluid environment

fick’s law of diffusion is simple passive diffusion from high concentration of solute to a low concentration of solute

149
Q

Membrane Permeability
what must a drug cross to get a biological response

do lipid-soluble drugs have a hard time passing cell membranes?

do lipid insoluble drugs have a hard time passing cell membranes?

A

Drugs must cross biological membranes to exert a biologic response

Lipid soluble drugs have little problem

Lipid insoluble drugs require additional assistance

150
Q

what is “Everted intestinal sac” used for

how does everted intestinal sac work

A

Used to evaluate absorption characteristics of drug substances

–A piece of intestine is removed from an intact animal, everted
–filled with drug to be tested and degree
–rate of passage of drug through membrane is determined

151
Q

what is partition coefficient (water and lipid)

what is octanol

what is water

P =

A

optimal balance between water and lipid solubility

octanol: (hydrophobic environment)

water: (Aqueous environment)

P = (conc. of drug un octanol)/(conc. of drug in water)

152
Q

when is the partition coefficient useful

antibiotics & fermentation broths

extracting drugs & therapeutic monitoring

absorption & dosage forms

flavoring oils. & oil/water emulsions

A

When recovering antibiotics from fermentation broth

When extracting drugs from biologic fluids for therapeutic monitoring

Absorption of drugs from dosage forms (ointments, suppositories etc..)

Study of distribution of flavoring oils between oil and water phases of emulsions

153
Q

How is the partition coefficient measured?

flask

phosphate buffer

HPLC

A

Shake a known amount of drug in a flask containing a measured amount of water and octanol.

Phosphate buffer (pH 7.4) is used to mimic physiological pH. This also corrects for the ratio of [conjugated base]/[acid] found in vivo.

The amount of drug in one or both of the phases is determined by HPLC (or by some other quantitative analytical approach).

154
Q

For octanol/water partition coefficients

what does it mean that it is lower than 1

what does it mean that it is higher than 1

A

lower than 1: hydrophilic

higher than 1: hydrophobic/lipophilic

155
Q

Pharmaceutics Ingredients and Excipients

One or more inactive agents are used to prepare final dosage forms

Flavors, and sweeteners:

Colorants:

Preservatives:

Stabilizers:

Diluents or fillers:

Binders:

Anti-adherents/ or lubricants:

Disintegrating agents:

A

Flavors, and sweeteners: improve taste

Colorants: enhances appearance

Preservatives: prevent microbial growth

Stabilizers: prevent decomposition

Diluents or fillers: to increase bulk

Binders: improves adhesive properties

Anti-adherents/ or lubricants: smooth coating

Disintegrating agents: promotes tablet breakup

156
Q

Reaction rates

what are the most common degradation processes, do we want them to happen

what is important for development of drug products and drug behavior

what is rate of reaction

what is the outcome of a drug

A

hydrolysis, oxidation—do not want to happen

Since drug therapy is a dynamic process, the time it takes for a reaction to occur is important for development of drug products, and drug behavior.

rate of rxn: Actual speed of velocity at which the dynamic process occurs

drug: Some Product, or Some Outcome
- Drug decomposition
- Drug dissolving in H20 to give solution
- Drug absorption
- Drug metabolism

157
Q

Chemically, drug substances are prone to hydrolysis or oxidation

what drug substances are prone to hydrolysis and what to oxidation

A

Prone to hydrolysis
Esters:
Amides
Lactones
Lactams

prone to oxidation
-Aldehydes
-Alcohols
-Phenols
-Sugars
-Alkaloids
-Unsaturated fats, oils

158
Q

Zero order reactions

what is the rate and does it change over time

what is ko

what eon will give you the amount of drug removed over any given period of time

A

In this reaction rate, the rate is a constant, and thus does not change with time.

The term ko is the zero order reaction rate

The amount of drug removed over any given period of time is a constant
= -kot + Co
used to calculate zero order rxn

159
Q

First-Order Reactions

what does it depend on

what happens to the rate when concentration (C) is large

what happens has C decreases

the higher the concentration, the water the what

what do most rxn with pharmaceutical products deal with

what eon is used to calculate first order rxn

The amount of drug removed each year decreases with time, but percentage or
the_____________________________

A

This reaction rate depends on the concentration of only one reactant.

Rate of reaction is initially fast when the concentration (C) is large; as C decreases the reaction slows as the reaction proceeds

The higher the concentration of drug the faster the rate process

Most reactions dealing with pharmaceutical products follow this process

lnc = -kt + lnCo

The amount of drug removed each year decreases with time, but percentage or
the fraction removed over this period of time remains constant

160
Q

A drug suspension (125 mg/ml) decays with zero order kinetics with a reaction rate constant of 0.5 mg/ml/hr. What is the concentration of intact drug remaining after 3 days (72 hrs)?

A

89 mg/ml/hr

161
Q

A drug suspension (125 mg/ml) decays with zero order kinetics with a reaction rate constant of 0.5 mg/ml/hr. How long will it take the suspension to reach 90% of its original concentration?

A

T = 25 hours

162
Q

A drug suspension (125 mg/ml) decays with zero order kinetics with a reaction rate constant of 0.5 mg/ml/hr. What its half-life (t1/2 )?

A

125 hrs

163
Q

What is the ingredient used in liquid and semi solid preparations to prevent the growth of microorganisms?

A

AntimicroBial preservative

B for:
Benzalkonium chloride

164
Q

The Pediatrician has clearly communicated to the compounding pharmacist that his patient is allergic to preservatives. Therefore, which of the following must NOT be used to prepare the Nasal Spray?

A) Butylparaben
B) Ethylparaben
C) Benzalkonium chloride
D) A and B only
E) A, B and C

A

the answer is E!

Butylparaben and ethylparaben are both anti fungal PRESERVATIVES and benzalkonium chloride is an anti microbial preservative

165
Q

where should the drug be in terms of MEC & MTC

what will happen if it was above the MTC

A

Ideally, the drug serum levels should be maintained above the MEC and below the MTC
.
* Concentrations above the MTC will cause toxic side effects

166
Q

What is the process from discovery/development of new chemical to postmarketing

*where is most of the time spent in the cascade

what happens to a lead drug

A

new chemical entity
–organic synthesis
–molecule modification
–isolating from plants

preclinical studies
–chemistry
–physical properties
–biological: pharmacology, ADME, toxicology
–preformulation

preclinical trials
–long term animal toxicity
–product formulation
–manufacturing and controls
–package and label design

clinical trials
–phase I
–phase II
–phase IIII

new drug application (NDA)
–submission
–FDA review
–preapproval plant inspection
–FDA action

postmarketing
–phase IV clinical studies
–clinical pharmacology/toxicology
–additional indications
–adverse rxn reporting
–product defect reporting
–product line extension

most time spent in clinical trials

Lead drug; preclinical testing; phase I,II,III, and then NDA submission

167
Q

Timeline for development of a new drug

preclinical research and development: ___ years

clinical–research and development: average ____ years

NDA review: average ____ years

average ___ years from initial synthesis to approval of NDA

A

preclinical research and development: 6 1/2 years

clinical–research and development: average 7 years

NDA review: average 1 1/2 years

average 15 years from initial synthesis to approval of NDA

post marketing surveillance

168
Q

percentage of drugs successfully tested

A

phase 1: 70%

phase 2: 33

phase 3: 25-30%

169
Q

Powder- a drug substance composed of what

what can it refer to - physical form or pharm. what

can it be used externally and internally?

how do many of the active and nonactive agents occur

A

A drug substance composed of finely divided particles

Term powder can refer to,
– Its physical form, or
– Type of pharmaceutical preparation

A type of pharmaceutical preparation, a medicated powder intended for internal (I.e., oral) or external (i.e., topical) use

Many of the active and non-active pharmaceutical agents occur in the solid state as amorphous powders or as crystal

170
Q

powders as a dosage form

powders are mixtures of what – are they wet, are they fine, are they drugs, are they for internal or external use?

what do powders consist of- in terms of particle sizes (very fine to very coarse)

what are the sizes of powders used to describe vegetable and animal drugs?

A

As a dosage form, powders are thorough mixtures of dry, finely divided drugs and excipients intended for internal or external use.

Powders consist of particles ranging in the size from 1 μm (very fine) to approximately 10 mm (very coarse).

– Very coarse
– Coarse,
– Moderately coarse
– Fine,
– Very fine

171
Q

how should the particle size be

how big should In the micron unit range
– Opthalmic suspension
– Oral suspensions
– Parenteral suspension
– Aerosols for lung
– Tablets and capsules-immediate release
– Topical aerosols
– Topical emulsions
– Topical suspensions

be

A

Particle sizes should be uniform

In the micron unit range
– Opthalmic suspension (≤10 )
– Oral suspensions (10-50)
– Parenteral suspension (0.5 to 25)
– Aerosols for lung (1 to 5)
– Tablets and capsules-immediate release (≤50) – Topical aerosols (50 to 100)
– Topical emulsions (≤50)
– Topical suspensions (10 to 50)

172
Q

what do the terms very coarse, coarse, moderately coarse, fine and very fine relate to

how is the passing powder particles through sieves accomplished and what is used

A

The terms very coarse, coarse, moderately coarse, fine, and very fine are related to the proportion of powder that can pass through standardized sieves of varying dimensions.

The passing of powder through standardized sieves is done over a specified time period under shaking, and generally with a mechanical sieve shaker

173
Q

Opening of Standard Sieves

what number is

very coarse
coarse
moderately coarse
fine
very fine

numbers go up, what happens to size

A

very coarse - No. 8 - 2.36 mm
coarse - No. 20 - 850 um
moderately coarse - No. 40 - 425 um
fine - No. 60 - 250 um
very fine - No. 80 - 180 um

numbers go up, size goes down

As the sieve number
Increases the size of the sieve
opening decreases

174
Q

As the sieve number _____ the size of the sieve opening _____

A

As the sieve number Increases the size of the sieve opening decreases

175
Q

Very coarse: No 8

A

All particles pass through a No.8 sieve and not more than 20% through a No. 60 sieve

176
Q

Coarse: No 20

A

All particles pass through a No.20 sieve and not more than 40% through a No. 60 sieve

177
Q

sieve sizes

  • Moderately Coarse: No.40
A

All particles pass througha No.40 sieve and not more than 40% through a No. 80 sieve

178
Q

Fine:No.60

A

All particles pass through a No.60 sieve and not more than 40% through a No.100 sieve

179
Q

Very Fine:No.80

A

All particles pass through a No.80 sieve and there is no limit as to greater fineness

180
Q

Bulk powders for external use

are they dry, free-flowing?

what are examples of them?

what are the advantages?- easy what, absorb what, dry what

what are the disadvantages?- may block what, get inhaled by who, not suitable for what

A

Usually dry, free-flowing preparations

– Finely powdered substances

– Ex: Chlorhexidine and Tinaderm
dusting powders

  • Advantages: easy application, absorb moisture, has dry
    cooling effect
  • Disadvantages: may block pores, get inhaled by infants, and not suitable for all skin-related medical problems
181
Q

Bulk powders for internal (oral) use

what does it resemble

advantages- stability, is it easily administered, does it absorb into the GI tract

disadvantages- is the accuracy of the dose guaranteed, it easy to carry, is it easy to mask unpleasant taste

A

Resemble dusting powders except given orally

– Preparations are formulated on the basis of dose-
weights [5 ml spoon = 5 grams ????].

Advantages: stability, easily administered (i.e.,
Indigestion powders), absorption by GI tract is rapid

Disadvantages:
– accuracy of dose not guaranteed, – large dose containers
– difficult to carry, and
– difficult to mask unpleasant tastes

182
Q

The particle size of a powder can influence…

dissolution
Suspendability
uniform distribution in what
penetrability of what
lack of grittiness of solid particles in what

A

Dissolution rate of particles

  • Suspendability of particles
  • Uniform distribution of a drug substance in powder mixture
  • Penetrability of particles
  • Lack of grittiness of solid particles in dermal ointments and creams
183
Q

Particle size of powders influence

the dissolution rate of particles- what can increase the rate of drug dissolution and its bioavailability

suspendability – particles are supposed to remain undissolved but what dispersed in a liquid vehicle

A

The dissolution rate of particles:
– micronization of particles can increase the rate of drug dissolution and its bioavailability

  • Suspendability:
    – Particles intended to remain undissolved but uniformly dispersed in a liquid vehicle
184
Q

Uniform distribution of a drug in a mixture or solid dosage form ensures what about dose

what does penetrability intend to do concerning the respiratory tract?

nongrittiness (smoothness) is found in what type of substances

A

Uniform distribution of a drug substance in a powder mixture or solid dosage form to ensure dose- to-dose content uniformity

  • Penetrability of particles intended to be inhaled for deposition deep in the respiratory tract (1-5 microns).
  • Nongrittiness of solid particles in dermal ointments, creams, and ophthalmic preparation (50 to 100 microns)
185
Q

what are the Methods used for determining particle size
S
S
L
L
M
C

A

sieving
sedimentation rate
light scattering
laser holography
microscopy
cascade impaction

A single method may be sufficient to determine the size for some powders but a combination is preferred.

In general a single method is usually sufficient

186
Q

Sieving

size range

A

Particles pass through a series of sieves of known successively smaller sizes

Size range:
* 40–9,500μm(micron)

187
Q

microscopy– grid used to do what

size range

A

A calibrated grid background is used to measure particle size

  • Size range:
  • 0.2-100μm
188
Q

Sedimentation rate:

A

– The velocity of particles through a liquid medium in a gravitational or centrifugal environment

  • Size range:
  • 0.8–300μm
189
Q

Light scattering:

A

– Reduction in the amount of light reaching the sensor as the particle dispersed in liquid or gas passes through the sensing zone range

  • Size range:
  • 0.02–2,000μm
190
Q

Laser Holography:

laser

aerosolized particle spray

photograph with camera

A

– A pulsed laser is fired through an aerosolized particle spray and photographed in three dimensions with a camera

  • Size range:
  • 1.4-100 μm
191
Q

Cascade impaction:

a particle is driven by what impacts what

particles are separated into various what by doing what

is there a specific size range for this? what makes this method special?

A

– A particle, driven by an airstream impacts on a surface in its path.
– Particles are then separated into various size ranges by successively increasing velocity of the airstream.

  • No specific size range
192
Q

Comminution of drugs

A

Grinding a drug in mortar to reduce its particle size

  • A mortar with rough surface (as opposed to a glass mortar) is used.

Trituration
* Levigation
* Levigating agent

193
Q

Trituration

A

The process of rubbing, crushing, grinding or pounding materials.

– May be employed to both comminute and mix powders

194
Q

Levigation

A

The process of reducing the particle size and grittiness

195
Q

Levigating agent

A

A small amount of some liquid added to the powder to form a paste

196
Q

Blending Powders

Generally when two or more powdered substances are to be combined to form a uniform mixture

S
S
T
T

what is the difference between levigating and tritulation

A

Spatulation
* Sifting
* Trituration
– Geometric dilution - add inert color to see if the mixture is uniformly distributed
* Tumbling

levigating - reducing particle size using a liquid and mortar
tritulation - reducing particle size using a mortar

197
Q

Spatulation

what is speculation used for

what is it not recommended for

what substances can form eutectic mixtures: MPCAT & similar chemicals

– What to add to avoid the formation of an eutectic mixture

A

A spatula moves through powders on a sheet of paper or ointment tile.

– Not recommended for large quantities

– used to mix solid substances that form eutectic mixtures, because little compression or compacting of powder with spatulation

– Substances that can form eutectic mixtures are: phenol, camphor, menthol, thymol, aspirin and similar chemicals

– What to add to avoid formation of eutectic mixture
- – Magnesium oxide
– Magnesium carbonate

198
Q

Trituration

what is it used for

how is it used

why is an inert color added

A

Trituration may be employed to comminute and mix powders
* Glass mortar is preferred if no need for
comminution
Why? Read section on pg 177
* During geometric dilution an inert color is added to ensure uniform distribution

199
Q

Sifting

how are powders mixed?

should you sift fluffy products?

A

In this method, powders are mixed by passing them through sifters

Sifting Fluffy products- no because it will get everywhere

  • Not acceptable for incorporation of potent drugs into a diluent powder
200
Q

Tumbling

what causes tumbling motion

where is it most widely used?

A

Tumbling powder enclosed in a rotating container

  • Special blenders mix/ blend powders by tumbling motion
  • Most widely used in the pharmaceutical industry
201
Q

Medicated Powders

what are aerosol powders good for

what are medicated powders?

how are most taken after mixing with what

what if you want to use it externally?

A

-Aerosol powders deliver medication deep within the lungs

-Inert propellants and diluents to increase flow properties and protect against humidity

Aerosol powders

  • Most taken orally after mixing with water
  • If intended for external use the label should
    read
    – EXTERNAL USE ONLY
  • Some intended to be inhaled into the lungs for local and systemic effects

Aerosol powders deliver medication
deep within the lungs

-Inert propellants and diluents to increase
flow properties and protect against humidity

202
Q

Quality control considerations

bulk powders
- what should pharmacists compare the final weight of the product to
- what should the powder be examined for – uniformity of what, particle what, flow, freedom from what

divided powders
- what should pharmacists compare the final weight of the divided powders product to
- what should the packets be checked for

A

Bulk Powders:
– Pharmacist should compare the final weight of the product to the theoretical weight.
– The powder should be examined for uniformity of color, particle size, flowability, and freedom from caking

  • Divided Powders:
    – Pharmacists should individually weigh the divided powders and
    then compare that weight to the theoretical weight.
    – The packets should be checked to see that they are uniform.
203
Q

Granules

are they regularly shaped, can they be forced into certain shapes

  • How are they prepared– screen, air, oven, mass formed
A

Prepared aggregates of smaller particles of powder

  • They are irregularly shaped, may be forced into certain shapes mechanically
  • First passed through a screen, then dried in air, then put in
    the oven and a pasty mass is formed

How are they prepared?
- First passed through a screen, then dried in air, then put in the oven and a pasty mass is formed

204
Q

Granules

  • how does the flow and size compare to powders
  • are they more easily or harder wetted by liquids
  • what are they prepared to contain
A

Characteristics

– Flow well when compared to powders

– Have a smaller surface area compared to powders of a comparable volume

– More easily wetted by liquids

– Prepared to contain colorants, flavorants and other pharmaceutical ingredients

205
Q

Effervescent Granules

these are granules that contain what in a dry mixture

what are these granules exposed to? make sure you know what they are exposed to for the exam!

how are the Effervescent granules produced?

  • Why important? what can the carbonated soln now mask
A

These are granules (coarse to very coarse powders) containing a medicinal agent in a dry mixture composed of sodium bicarbonate, citric acid, and tartaric acid

  • When water is added carbon dioxide is liberated and sparkles (and bubbles) are produced
    add water, releases CO2, sparkles are produced
  • Why important?
    – Because the carbonated solution produced can now mask undesirable tastes associated with drug
206
Q
A

P1 Fall 2023 (66 decks)

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