pharm final exam review part 1 :) Flashcards
What is NF and USP?
Why was it critically important to adopt these legal documents?
what do these stand for
the united states pharmacopeia and national formulary
USP/NF
There was 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
The first one was made in 1820
important to adopt because:
- it adopts standards for drugs, pharmaceutical ingredients, and dosage forms
– Reflects the best current practices of medicine
– Provides information on tests and assay procedures for demonstrating compliance with these standards
– For individual components, not combinations
What is the function of the CDER?
what does it stand for
Center for Drug and Evaluation Research (CDER)
Function
- assesses the benefit-to-risk relationship of a drug
- asks the question: is a drug safe and effective enough
- makes drugs available to the public sooner
- provides clear standards for drug evaluation
- has high priority drugs: these are defined as drugs that offer a significant medical advantage over current therapies
balancing risks vs benefits
The major difference between the FDA of 1906 and the FDA of 1938
Food and Drug Act of 1906:
- The first law to require drugs to be of correct strength, purity, and quality
Food and Drug Act of 1938:
- now: correct strength, purity, quality and be safe
What is the name of the agent that caused the Sulfanilamide Tragedy?
Was the problem ingredient an excipient or an active agent?
(i) What was the finished preparation intended to treat?
(ii) Could this tragedy have been prevented? How?
agent that caused the tragedy:
diethylene glycol, antifreeze for cars :(
the problem was with the excipient which was diethylene glycol
The sulfanilamide drug was an antibiotic intended to treat bacterial infections
(ii) Could this tragedy have been prevented? How?
- yes, use a safer excipient
Who was Frances Kelsey,
why did President Kennedy award her the Distinguished Federal Civilian Service Award?
she refused to authorize thalidomide for the market because she had concerns about the lack of evidence regarding the drug’s safety
As a result of her blocking American approval of thalidomide, Kelsey was awarded the President’s Award for Distinguished Federal Civilian Service by John F. Kennedy on August 7, 1962, becoming the second woman so honoured. After receiving the award, Kelsey continued her work at the FDA.
Black Box Warning:
FDA’s absolute strongest labeling requirements are used for the highest-risk medications
purpose:
– It stresses 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.
Kefauver Harris Amendment of 1962:
Thalidomide Tragedy was the main reason behind the development of this Act.
required manufacturers to prove a drug to be both safe as well as efficacious before granting FDA approval for marketing – went a step forward from FDA 1938 and required efficacy
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.
Durham-Humphrey Amendment of 1952:
no refills (dispensing of drugs) without a valid Rx
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.
Complete the sentence regarding the code of federal regulations (see text book). The publications provide the most definitive information on the……. ____________________________________________________________________.
federal laws and regulations pertaining to drugs
Can a Drug Product Recall ever be initiated by the manufacturer? Discuss..
yes! If it is revealed that the 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: products that violate federal regulations but are unlikely to cause adverse health consequences.
FDA does not like to do this but will allow the company to recall it
so answer: both of them, FDA & manufacturer!
The manufacturer must initiate it. Although the FDA can order manufacturers to recall medical devices, vaccines and nicotine products, the agency cannot force a company to recall defective or potentially harmful drugs.
Name the natural plant source from which the following alkaloid drug agents were originally derived?
Morphine _______________________
Quinine _______________________
Digitalis _______________________
Belladonna _______________________
Morphine - opium poppy
Quinine - cinchona bark
Digitalis - foxglove
Belladonna - deadly night shade
If we have a lead compound why continue searching for the goal drug?
because the lead compound is the closest thing to the goal drug and we will need to develop the lead compound further to make it the goal drug
the goal drug is the hypothetical in-a-perfect-world drug that has the lowest administration, best elimnation from body and etc and we want to continue searching and developinh for the lead compound to become the goal drug
Why is the partition coefficient important in pharmaceutics?
Because we want to make sure that the drug has enough lipophilicity or hydrophilicity in order to cross the cell membrane or carried through the cell.
To ensure this, we need to determine the partition coefficient which offers a range of how lipophilic or hydrophilic the drug is and can give us the indication to either keep the drug the way it is or change the properties to make it more lipophilic or hydrophilic
What is the significance of the Crystal and Amorphous drug form?
Crystal
- antibiotics like penicillin are more active due to better stability over an amorphous state
- PCN crystal form results in a better therapeutic response
amorphous
- more soluble
- some antibiotics like Novobiocin
Chloramphenicol is inactive in the amorphous form
How are
Phase I,
Phase II and
Phase III Clinical Trials different?
Phase I Clinical Trials
- safety in 20 - 100 patients
- less than a year (brief)
- Purpose is to determine toxicology, metabolism, and pharmacologic actions
Application contains:
- The plan for the study
- Chemical Structure
- Animal testing results
- Manufacturing information
Phase II
- To determine the 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
Phase III
- To demonstrate long-term safety & efficacy of drug product; to discover drug’s efficacy standards
- 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?
- The investigational drug will be used in several randomized, controlled studies in various clinical research facilities including,
- by this stage, Formulation and adjustments known by the start of phase III
- only the excipients can be changed
- Why make changes: good for the drug. May have found out that if you substitute an excipient and make it work better
Can new clinical trial material (CTM) be introduced at a phase other than Phase I? If so, with all of our concerns regarding drug regulation and control, why do you think this is allowed? Weigh the benefit versus the risk.
yes, there are different CTMs for each phase
phase I
- uses extemporaneous formulations - requires no preparation
phase II
- same dosage form as phase I except:
— When required dosage strength is not supported
—-When medium-to-large scale is not feasible
—-Alternatively, a new formulation closer to the desired commercial dosage form can be introduced during Phase II
phase III
- may require a different dosage form than II to give better dosage strength
benefit: can improve dosage form and vehicle for the drug to be more effective
risk: could impact the safety of the drug and make unsafe and if it used after phase I then, the safety has already been proven for a different form so introducing a whole new one could pose some additional risks
by phase III, all of the formulatipns have been set and you can only change the excipient to make the drug better
What is the major problem with dosing below the MEC and above the MTC?
Concentrations below the MEC will be ineffective so will have to use more drugs to get desired effect
Concentrations above the MTC will cause toxic side effects
What is the difference between the Prophylactic Dose and the Therapeutic Dose?
Prophylactic dose: Administered to prevent patients from contracting the disease
Therapeutic dose: Administered once disease has been contracted
What is the difference between Batch and Batchwise control?
batch: a specific quantity of a drug of uniform specified quality produced according to a single manufacturing order during the same cycle of manufacture
1 set of products with uniform quality and quantity
batch-wise control: 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
What is the difference between Lot and Lot number?
lot: A batch or any portion of a batch having uniform specified quality and a distinctive identifying lot number.
batch becomes a lot when assigned lot number
lot #: 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.
What is the name of the regulatory process through which industry measures quality performance, and compares to standards?
Quality control
Quality Unit
Quality assurance
Quality control unit
Quality control
YEAH!!!!!!!!! GREAT JOB YOU WILL ACE ALL OF YOUR FINAL EXAMS IN JESUS NAME AMEN!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
During the Production and Process Control written documentation is required to make sure that each drug product has the correct,
_________________, Strength, __________________ and Purity
Identity
Strength
Quality
Purity
Review notes and textbook chapter on Tamper-evident packaging.
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
Tamper-evident packaging
- film wrapper
- blister/strip pack
- bubble pack
- shrink seal, band
- foil, paper, plastc pouch, bottle seal
- tape seal
- breakable cap
- sealed tube
- sealed carton
- aerosol container
What are the major problems associated with the use of Plastic versus Glass containers for the packaging of finished pharmaceutical preparations? Be specific.
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 overtime
What is required for OTC labeling?
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
- 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
What are the storage temperatures as defined by USP?
_____________ = 8 ºC
Cool = _______________
____________ = 22 ºC
Warm = _______________
____________ = Above 40 ºC
Cold: 8 ºC
Cool: 8 ºC - 15 ºC
Room temp: 20 ºC - 25 ºC
Warm: 30 ºC - 40 ºC
Excessive Heat: Above 40 ºC
Biologics are stored at what temperature range? ______________________
2ºC and 8ºC
Why are dosage forms necessary in Pharmacy?
1)
2)
3)
4)
5)
6)
7)
1) To provide protection from destructive chemical influences (atmospheric oxygen, humidity…)
2) To provide protection from gastric pH
3) To address offensive taste or odors
4) To provide liquid preparations
5)To control the rate of drug release
6) To improve drug action
7) To provide for insertion into the body’s orifices
How is the melting temperature of a drug product typically determined?
What influence (if any) can the contamination of a drug agent have on the melting temperature?
melting point can be used to determine the purity
is determined using DSC = Differential Scanning Calorimetry
contamination will lower the melting point
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) decreases.
What is the relationship between particle size and dissolution?
dissolution rate will ↑ with ↓ in particle size
What is a eutectic mixture? How can the formation of a eutectic mixture be avoided?
Minimum melting point = EUTECTIC POINT
keep the compound pure and non-contaminated with anything
Define polymorphism? Provide examples including specific drug names and actions.
the ability of a solid material to exist in two or more crystalline forms
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” so The amorphous form of the drug is more soluble than the crystal form
examples
- Antibiotic substances
Novobiocin
Chloramphenicol
are inactive in crystal form but active in the amorphous form
Crystal drugs can be more active due to better stability over an amorphous state
- Penicillin G
Its crystal form results in a better therapeutic response
What is the difference between zero-order and first-order reaction rates
what are their equations
Zero order: In this reaction rate, the rate is a constant, and thus does not change with time.
- a chemical reaction wherein the rate does not vary with the increase or decrease in the concentration of the reactants.
- does not depend on [ ] of reactants
first order
- chemical reaction for which the reaction rate is entirely dependent on the concentration of only one reactant.
zero order eqn:
[A] = – kt + [A]0
first order eqn:
ln[A] = -kt + ln[A]0
first order is the ln of the zero order!
Make sure that you are familiar with the first three pharmaceutical excipients under each of the major categories? Expect approx.4 questions on final exam.
Describe Very Coarse, Coarse, Moderately Coarse, Fine and Very fine powders in terms of sieve numbers. Which category do Granules belong?
Very coarse - No 8, Allparticlespass through a No.8 sieve and not more than 20% through a No. 60 sieve
Coarse- No 20, All particles pass through a No.20 sieve and not more than 40% through a No. 60 sieve
Moderately coarse- No 40, All particles pass through a No 40 sieve and not more than 40% through a No. 80sieve
Granules are coarse to very coarse powders
Fine- No. 60 All particles pass through a No.60sieve and not more than 40% through a No. 100 sieve
Very fine- No 80, All particles pass through a No.80 sieve and no limit as to greater fineness
Why granules over the use of powders when preparing effervescent salts?
because powders are more fine than granules, so it would dissolve too quickly and hard to control
the granules will dissolve slowly be able to have the time to form the effervescnet salts to dispell offensive taste
at least that is what I remember
citric acid and tartarric acid, alone they will not produce a powder with good effervescent
citirc acid will be too sticky
tartaric will be = crumbling
List name of methods used to determine particle size?
How many of them are required to accurately determine the size of a formulation product?
Sieving
Microscopy
Sedimentation rate
Light scattering
Laser holography
Cascade impact ion
should be all of them except cascade impact because they all have size ranges except for cascade
Geometric Dilution:
During geometric dilution, an inert color is added to ensure uniform distribution
When mixing a small amount of a drug with a large amount of another ingredient or diluent, the process of geometric dilution is used. In this method the drug present in smaller quantity is placed in the mortar with an equal amount of the other ingredient. The two materials are triturated until they are well mixed.
Trituration
The process of rubbing, crushing, grinding or pounding materials
May be employed to both comminuted and mix powders
Glass mortar is prefers if no comminuted during geometric dilution, inert color is added to ensure uniform distribution
communition: the reduction of solid materials from one average particle size to a smaller average particle size, by crushing, grinding, cutting, vibrating, or other processes.
Levigation
The process of reducing the particle size and grittiness
Levitating agent: a small amount of some liquid added to the powder to form a paste
Spatulation
A spatula move through powers on a sheet of paper or ointment tile
Not recommended for large quantities
Ideally suited for mixing solid substances that form eutectic mixtures because little compression or compacting of powder with spatula toon
Substances that can form eutectic mixtures are: phenol, camphor, menthol, thymine, aspirin and similar Chemicals
What do add to avoid formation of eutectic mixtures
Magnesium oxide
Magnesium carbonate
Sifting
In this method powders are mixed by passing them through sifters not acceptable for incorporation of potent drugs into diligent powder
Tumbling
Tumbling powders enclosed in a rotating container
Special blenders mix/blend powders by tumbling motion
Most widely used in pharm. industry
out all of these which one do pharmacists mostly use
Geometric Dilution:
Trituation:
Levigation:
Spatulation:
Sifting:
Tumbling:
tumbling (?)
refer to card 43
You should know all of the different capsules and tablets as mentioned previously.
Compressed tablets (C.T.):
- usually contain the following in addition to medicinal agents
Diluents or Fillers: Add bulk to prepare a certain size
* Binder or Adhesives: Promote adhesion of the particles
of the formulation
* Disintegrants: Promotes breakup of tablets/drug availability
* Antiadherents/ glidants/ or lubricating agents
* Miscellaneous Adjuncts: Colorants and flavorants to
enhance overall appearance
Multiple compressed tablets (M.C.T.):
More than a single compression
* Produces multiple-layered tablet or a tablet within a tablet
* Each layer may contain diff. medicinal agents.
Why? * Separation may be required to avoid chemical and
physical incompatibility
* Staged drug release
* General appearance of multiple-layered tablet
Sugar-coated tablets (S.C.T):
Compressed tablet can be covered with a colored or an uncolored sugar layer
– The coating is water soluble
– The coating is quickly dissolved after swallowing
– The coating protects the enclosed drug from the environment
– The coating enhances the general appearance of tablets and permits imprinting of identifying manufacturer’s info.
Disadvantages to sugarcoating tablets are,
– the time and expertise required in the coating process,
– the increase in size, weight, and shipping costs. * May be 50% larger and heavier than uncoated tablets
Film-coated tablets (F.C.T.):
These compressed tablets are coated with a thin layer of a polymer capable of forming a skin-like film over the tablet
* Usually colored
* More durable, less bulky, and less time consuming to apply than sugar-coatings.
* Designed to rupture and expose the core tablet at the desired location within the gastrointestinal tract
Gelatin-coated tablets:
Capsule-shaped compressed tablets
– Facilitates swallowing and compared to unsealed capsules, gelatin tablets are more tamper-evident
Enteric-coated tablets (E.C.T.):
Have delayed release characteristics
* Designed to pass unchanged through stomach intestines where the tablets disintegrate and allow drug dissolution.
* Mainly used when by-passing
the stomach to improve drug absorption
Buccal or sublingual tablets:
These are flat, oval tablets intended to be dissolved in the buccal pouch, or beneath the tongue through absorption through the oral mucosa
– An alternative for drugs that are poorly absorbed from the G.I. Tract
– Buccal tablets designed to erode slowly
– Sublingual tablets designed to provide rapid release
Buccal: In direction of the cheek Sublingual: Below or beneath the tongue
buccal drug delivery :
The dosage form must remain in place
* Total area of absorption is low compared to
other routes- 100 to 170 cm2
– Taste must be bland, or not acceptable for use – must also be a non-irritant
– Drug should not discolor or erode teeth
sublingual drug delivery:
Lining of the epithelium is keratinized for buccal and
sublingual, but the epithelium for sublingual is thinner.
* What does this tell us about drug absorption? - faster than buccal!
Instant Disintegrating/ Dissolving tablets
Extended-Release Tablets (E.R.)
Vaginal Tablets:
Also called vaginal inserts
* Uncoated and bullet or ovoid shaped tablets * Inserted in vagina for localized effects
– Antibacterials for the treatment of Vaginitis caused by Hemophilus vaginalis or
– Antifungal for treatment of vulvo vaginitis candidiasis caused by Candida albicans and related species
types of capsules:
Enteric coated (these are designed to pass through the stomach for drug release and absorption in the intestine)
Extended Release Dosage Forms: These are designed to provide release of the medication
Hard Gelatin Capsules:
Used to manufacture most of the commercially available medicated capsules
– Empty capsule shell made from: * Gelatin, sugar and water
* They are clear, colorless, and essentially tasteless
* Most contain colorants & opaquants to make distinctive
Gelatin is soluble in hot water and in warm gastric fluids
* Given that gelatin is a protein it is digested by proteolytic enzymes and absorbed
* Whengelatindissolvesitexposesitsmedicinal contents to the gastric (or intestinal) bodily fluids
* Most are colored with FD&C and D&C dyes and made opaque by adding titanium dioxide.
Hard capsules: contains between 13-16% moisture, but poor storage conditions can increase this level. Not good!
Soft Gelatin Capsules:
Pharmaceutically elegant and easily swallowed
* Prepared to contain liquid, paste & dry fills
– Liquids that can easily migrate through the capsule shell cannot be encapsulated into soft gelatin capsules.
* When not to be used?:
– When water content is > 5%
– When low molecular weight water soluble and
organic compounds are employed such as, * alcohols, ketones, amines, and esters.
* Preservatives such as methylparaben and/or
propylparaben used to retard microbial growth
What are physiological factors influencing gastric emptying?
How recently you ate
If you ate shortly before, there are contents in your stomach and gastric emptying will be slow and the pill will not be absorbed as quickly
If you ate a while ago, there are not as much contents in your stomach and thus gastric emptying will be faster and the pill be absorbed sooner
What influence (if any) will dosing before and after a meal have on the fraction of dose remaining in the stomach?
before a meal:
the drug will absorb faster because there is little to no content in the stomach
after a meal:
the drug will absorb slower because there is more content in the stomach
Describe the 4 major transdermal drug delivery systems (TDDS) discussed in class.
Fentanyl patch
- Dose: Fentanyl 25 µg/hr
- Treatment: 72 hrs
- Where applied: Apply the patch to a dry, flat skin area on your upper arm, chest, or back.
- This medicine is a tan, square,
transdermal system imprinted with “FENTANYL 25 mcg/hr”.
- Caution: “Do not use the patch form of fentanyl to relieve pain that is mild or that will go away in a few days. This medication is not for occasional (“as needed”) use.”
Transdermal estradiol
- Dose: 0.05 or 0.1 mg estradiol per/day
- Treatment: 3 weeks of treatment followed by one without and so forth
- Patients are provided with 17-β estradiol for conditions associated with menopause, primary ovarian failure, etc…
- Oral delivery is a problem, Why?
Estradiol –> Estrone
- Where applied?
lower stomach area, below your waistline
Transdermal nicotine
Dose: 7 to 22 mg of nicotine per/day
Treatment: 6-8 wks
- Should be replaced daily
- Should be discarded immediately after use
- Patients are provided with sustained levels of nicotine in blood
Where applied?
- Arm or upper front torso
Transdermal-scopolamine: Novartis
- Used to provide controlled release of scopolamine over a 3 day period
- Used to treat nausea related to travel, particularly by sea
- Where applied?
Behind the ear.
- One patch removed and another can be applied when desirable
- Backing:
- Aluminized polyester film
Drug reservoir contents:
- Scopolamine, mineral oil, and polyisobutylene
Transdermal-nitro: Novartis
- Used to provide controlled release of nitroglycerin.
- Used to treat angina.
- Where applied?
Chest and upper arm of shoulder areas
Backing:
- Aluminized plastic
Drug reservoir content:
- Nitroglycerin adsorbed on lactose, colloidal silicon dioxide, and silicone medical fluid
What is the ideal drug candidate for transdermal delivery in terms of molecular weight, lipophilic-hydrophilic character?
Non-polar drugs tend to cross the cell barrier through the lipid-rich regions (transcellular route), whereas the polar drug favor transport between the cells (intercellular route)
The drug should have some aqueous and lipophilic character
Low MW: MW (molecular weights) between 100 and 800 are favored
38) Under what circumstances will the skin be the rate-limiting step during percutaneous absorption?
normally, the rate-limiting step in this process is diffusion through the stratum corneum,
but in the lecture, factors that affect percutaneous absorption are:
Physical and chemical properties of the skin
Molecular weight
Solubility and Pka
Partitioning coefficient
Nature of the carrier vehicle
Condition of the skin:
Age
Temperature
Site of administration
Race (Pigmentation -Dark and white skin)
Disease (i.e., Psoriasis)
surface area
[drug]
physiochemical attraction to skin
MW between 100 and 800 are favored
skin hydration will favor absorption, thin horny layers are preferred
longer contact with skin
Briefly discuss when you would use an ointment, gel and cream?
Ointment: if you want protectant, emollients, lubricants effect, for dry and scaly skin surfaces
Cream: easily removed, weeping or oozing
Ointments contain the most oil, making them the best choice for extremely dry, cracked skin. Creams have some oil, while lotions and gels contain more water.
Gel: have high viscosity
What are the 4 major ointment bases? Which is most oleaginous and most hydrophilic?
Oleaginous - most oleaginous
Absorption
Water removal
Water soluble - most hydrophilic
Solid or semisolid & Application
Creams
Gels
Pastes
Plasters
Glycerogelatins
Creams : semisolid, applied to weeping or oozing surfaces. Used topically, rectally, vaginally. Easily removable
Gels: semisolid, skin, eye, nose, vagina, rectum
Paste: semisolid, used to absorb serous secretion, remaining in place after application
Plaster: solid or semisolid, used for adhesive tape. If unmedicated: provide protection or mechanical support at application site. Medicated: concentration of salicylic acid used in commercial plasters (range from 10-40%) for the treatments of corns of feet
Glycerogelatin: solid, plastic masses of gelatin, glycerine water and medicinal substances. Applied to skin for long term
Review Incorporation method and Fusion Methods for the preparation of Ointments.
Incorporation of solids
Use stainless steel spatula except when ingredients react with the stainless steel material (i.e., iodine). A Rubber spatula can replace stainless steel in this case.
Thorough rubbing and working of the components together on solid surface until smooth and make preparation uniform.
Now separate freshly prepared base from the fine powder components used in the previous mixing step.
Add small amount of each together and mix until uniform.
Continue until all powder and base are combined and uniformly blended.
Levigation is often used to reduce powder particle size to reduce grittiness prior to incorporation of the solid material into the base.
For the selection of levigating agents.
Levigating agents should be physically and chemically compatible with drug and base.
Mineral oil is used for when oil is the external phase,
Glycerin is used when water is the external phase.
For incorporation of liquids…consider the capacity of ointment base
Note difference between oleaginous –vs- hydrophilic ointment
How to incorporate liquids into hydrophobic base?
Add solution to minimum amount of hydrophilic base, and then
Add this freshly prepared mixture to the hydrophobic base.
Small volumes of alcoholic solutions can be added to oleaginous vehicles or emulsions with ease. For example
(Fusion method)
* By this method, “all or some of the components of an ointment are combined by being melted together and cooled with constant stirring until congealed”
* Main methods of fusion:
– Heat-sensitive or volatile components are added when the temperature of mixture is low enough not to cause decomposition or volatilization.
– In general, components having the highest melting points are heated to the lowest required temperature to produce a melt
– Two Alternative methods:
1) Melt the component with the lowest melting point first, followed by the
addition of the remaining components in order of their melting points.
2) Melt all components simultaneously, increasing the temperature only as
needed
Review the containers used for packaging.
Topical dermatologic preparations-
packaged in either jars, tubes or syringes
Ophthalmic, nasal, vaginal and rectal preparations-
packaged in tubes or syringes
What is the difference between an O/W and W/O emulsion?
When is each used?
Provide synonyms for internal and dispersed phase, and label a diagram below depicting each component.
O/W is oil droplets dispersed through water medium
W/O is water droplets in oil medium
type I: permit the incorporation of aqueous solutions, producing water-in-oil (w/o) emulsions (e.g., hydrophilic petrolatum*)
Type II: water-in-oil (w/o) that permits additional aqueous solutions (e.g., lanolin).
Use O/W for water removable bases
Internal phase = dispersed phase
external phase = continuous phase
Sedimentation Rate of particles of a suspension. What is the equation?
Is the density of the medium higher or lower than the density of a particle, and why is this important for a finished formulation product?
dx/dt = (d^2(pi-pe)g)/18n
Density of the particle is higher than density of the medium (which is lower)
This is important because we want to keep the particle in suspension as much as possible and….
What are the different Antacid oral suspensions and problems associated with each?
Sodium bicarbonate (SB):
Neutralizes acid effectively.
However, can produce sodium overload and systemic alkalosis.
Magnesium preparations (MP):
Neutralizes acid effectively.
However, can cause diarrhea and cause problems for patients with renal impaired function.
Calcium carbonate:
Neutralizes acid effectively.
However, can also cause hypercalcemia and stimulation of acid secretion (acid rebound).
Aluminum hydroxide:
Neutralizes effects slowly, and not as well as SB or MP.
However, excessive use may lead to constipation and phosphate depletion, resulting in muscle weakness, bone resorption and hypercalciuria
Fusion method for ointments
By this method, “all or some of the components of an ointment are combined by being melted together and cooled with constant stirring until congealed”
Main methods of fusion:
Heat-sensitive or volatile components are added when the temperature of mixture is low enough not to cause decomposition or volatilization.
In general, components having the highest melting points are heated to the lowest required temperature to produce a melt
Two Alternative methods:
Melt the component with the lowest melting point first, followed by the addition of the remaining components in order of their melting points.
2) Melt all components simultaneously, increasing the temperature only as needed
What is the purpose of the lipids DSPC
Used for delivery of mRNA, active material to the cells. If not, you will probably get absorption and such but you will get more delivery of the avctive substance
PEG is a long chain, enhances circulation and half-life
PEG is conjugated to the lipid
At the head group, get a long chain
PEG with a lipid and they both are responsible for the delivery of the drug to the site
Which of the following best describes the process of grinding a drug in a mortar to reduce its particle size)?
A. Sifting
B. Spatulation
C. Trituration
D. Blending
C. Trituration
What are situations when you might want to grind particles rather than blend them only?
reduce particle size
to get a more homogenous mixture
Powders can be blended by all of the following EXCEPT?
A. Dissolution
B. Spatulation
C. Tumbling
D. Blending
A. Dissolution
What are situations when you might want to grind particles rather than blend them only?
Spatulation is preferred for mixing solid materials that form eutectic mixtures.
true
false
true
Why is spatulation preferred for mixing solids to avoid the formation of eutectic mixtures?
- What are two ways to use magnesium carbonate to prevent the formation of eutectic mixtures?
little compression or compacting of powder with spatulation
if you add inert color, Magnesium oxide and Magnesium carbonate to pure A and pure B, you will avoid eutectic mixtures – you use one or the other, you do not use both
Why employ the geometric dilution method in pharmacy?
A. To reduce powder size
B. To achieve uniform mixing
C. For comminution purposes
D. All of the above
E. None of the above
B. To achieve uniform mixing
yes! geometric dilution enables uniform distribution of the resulting compound with the drug.
CDER Glossary definitions
clinical trials -
human studies are designed to distinguish a drug’s effect from other influences like a spontaneous change in disease progression or a placebo effect. such studies conducted in the U.S. must be under an approved IND and by FDA rules on human studies and informed consent
Investigational New Drug (IND) -
an application that a drug sponsor must submit to the FDA before beginning tests of a new drug on humans. The INND contains that plan for the study and is supposed to give a complete picture of the drug, including its structural formula, animal test results, and manufacturing information
new drug application -
an application requesting FDA approval to market a new drug for human use in interstate commerce. The application must contain, among other things, data from specific technical viewpoints for CDER review - including chemistry, pharmacology, medical, and biopharm….
phase I
the first trials in humans that test a compound for safety, tolerance, and pharmacokinetics. The trials usually employ normal, healthy volunteers
phase 2
pilot studies to define efficacy and safety in selected populations of patients with the disease or condition to be treated, diagnosed, or prevented. Dose and dosing regimens are assigned for magnitude and duration of effect during this phase
phase 3
expanded clinical trials intended to gather additional evidence of effectiveness for specific indications and to understand safety and drug-related adverse effects better
phase 4
studies performed after a drug is approved for marketing. The studies are performed to determine the incidence of adverse reactions; to determine the long-term effect of a drug; to study a patient population not previously studied; and for marketing comparison against other products and other uses
postmarketing surveillance
FDA’s ongoing safety monitoring of marketed drugs
preclinical studies
studies that test a drug on animals and other nonhuman test systems.
Techniques used to evaluate liposome accumulation in tumors
In vivo Video Microscopy
Electron Microscopy
In vivo Biologic Distribution of Doxorubicin
In vitro uptake studies
Statistical Analyses
