Exam 1 Flashcards
1
Q
Pharmaceutics
A
Discipline of pharmacy that deals with the process of turning New Chemical Entity (NCE) into medication that can be safely used
science of dosage form and design
formulation of pure drug substance into dosage form
2
Q
Branches of Pharmaceutics
A
Pharmacokinetics Pharmacodynamics Pharmacogenomics Bio-pharmaceutics Pharmaceutical Technology
3
Q
Drug
A
Agent intended to diagnose, treat, prevent, cure, or mitigate a disease
4
Q
Drug product
A
whole pill, active ingredient (drug) plus excipients
5
Q
Drug preparation
A
Extemporaneous compounding, compounding active ingredient into another usable form
ex. crushing tablet to be put into a solution
6
Q
Hippocrates
A
The father of medicine, introduced scientific systematized medical knowledge
7
Q
Dioscorides
A
author of De Materia Medica
botanist who studied naturally occurring medicinal materials
8
Q
Galen
A
Galic pharmacy, galenicals
wrote naturally occurring vegetable drugs and formulations for patient admin
took bunch of drugs, put into one formulation (poly pharmacy), idea that body will take what needs and get rid of the rest
9
Q
Paracelsus
A
match specific drug to specific disease
changed pharmacy from botanical science to one based on chemical science
10
Q
Karl Wilhelm Scheele
A
- Independently discovered lactic acid, citric acid, oxalic acid, tartaric acid, arsenic acid, glycerin, calomel, benzoic acid, oxygen
11
Q
Friedrich Serturner
A
morphine
12
Q
Joseph Pelletier and Joseph Caventou
A
Quinine, cinchonine, brucine
13
Q
Joseph Pelletier and Pierre Robiquet
A
caffeine
14
Q
Pierre Robiquet
A
codeine
15
Q
Jonathan Roberts
A
First hospital pharmacist
16
Q
USP
A
U.S Pharmacopeia, established drug standards
formed 1820, revised every year currently
17
Q
proprietary name
A
brand name
registered trademark
18
Q
Non-proprietary name
A
generic, common name
USAN Council, WHO
19
Q
Generic Product
A
product which is a copy of brand drug product, made of the same active ingredient(s), strength, dosage form
20
Q
Why do we need drug standards?
A
to make drugs reproducible, same ingredient, amount every time you make
21
Q
Dr. Lyman Spalding
A
Father of the USP
22
Q
NF
A
National formulary, included drugs denied admission to USP
23
Q
USP-NF
A
strength, quality and purity were recognized as official. combined in 1980
24
Q
Components of UPS-NF
A
Monographs: standards of all drug substances, dosage forms, and compound preparations (USP) and standards for excipients (NF)
General Chapters: tests/procedures described In detail ie 797 (sterile) 795 (non sterile)
General Notices: definitions of terms in monographs
25
USP <795>
Non sterile compounding
| 3 categories: simple, moderate, complex
26
Master formulation
"master recipe"
includes name, strength, dosage form, mixing instructions
created before compounding a preparation for the first time, followed every time it is made
27
Compounding record
"log book" or "Journal"
includes name, strength, dosage of prep, total quantity, name of person who prep, BUD, Lot/Exp
Defective product log must be kept in pharmacy, products reported
28
Order of ingredients
USP, NF = best grade
| FCC and ACS
29
USP 800
safe handling of hazardous drugs. covers just about everything in the process, from getting it, to admin, to waste
30
Food drug act of 1906
drugs have to meet standards for strength, purity and quality
31
Sherley Amendement 1912
prohibits misleading therapeutic claims
32
Federal Food, Drug and Cosmetic Act of 1938
results of Sulfanilamide incident
Drugs have to show safety testing
FDA can come inspect whenever
Adequate labels and directions
Cant distribute drug without NDA filing and approval
33
Durham-Humphrey Amendment of 1952
no refills without valid prescription
determined what Rx only and OTC drugs are
duties of pharmacist
34
Kefauver-Harris Amendments of 1962
Response to Thalidomide
Need to file IND
required drug to be proven safe and efficacious
grandfathered drugs 1906 -1938
Manufacturers must record and report adverse events
established GMPs
35
Comprehensive Drug Abuse prevention and Control Act of 1970
5 Schedules of drugs I-IV
Schedule I - no medical use
Schedule II - medical use, high abuse potential
36
FDA Pregnancy Categories
Categories assigned in 1979, A,B,C,D,X
37
Black box warning
Used for high-risk drugs, such as antidepressants
38
Pregnancy and Lactation Labeling Rule PLLR
package inserts have to include new headings
Pregnancy
Lactation
Females and Males of reproductive potential
39
Drug Listing Act of 1972
Established NDC (4-4-2, 5-4-1, 5-3-2)
each firm that manufactures or repackages drugs must register with FDA
40
NDC
Labeler code: Manufacturer/distributer (segment 1)
Product code: Drug formulation (segment 2)
Package code: Package size/type (segment 3)
41
Orphan Drug Act of 1983
enabled FDA to promote research and marketing for drugs needed for rare disease
gave incentives to develop orphan drugs to drug companies
42
Drug price Competition and Patent Term Restoration Act of 1984
Increased patent to 20 years
Speed up FDA approval of generic drugs, ANDA
43
Prescription Drug Marketing Act of 1987
Dingell Bill
prohibit drug reimportation
Sales restrictions
sample distribution
wholesaler distributors
44
Dietary Supplement Health and Eduction Act of 1994
DSHEA
regulated labeling claims for supplements
not legally considered drugs
can choose to be USP verified, adhere to USP-NF standard
45
FDA modernization act of 1997
Accelerated approval new drugs
Expand patient access to investigational treatment for life-treating diseases
codify FDA info
46
Drug product recall
Class I,II,III
I: most severe, likely hood of serious adverse events or death
II: may cause temp health consequences, can be treated, most common
III: not likely to cause adverse health consequences, most likely not related to drug
47
CDER
Watchdog
can determine what drugs are high priority, speeding up approval
48
Stages of drug development
```
Initial idea
Research
Development
regulatory approval
Marketing approval
Post launch studies
```
49
goals of nonclinical development
binds to intended target
acceptable safety profile based on tolerability in animals
chance of showing efficacy in humans
data used to determine dose and dose range for clinical trials, parameters for adverse effects
50
Primary Pharmacology
study mechanism of action of a drug
51
Secondary pharmacology
study off target effects of a drug
52
Pharmacokinetics
what body does to drug, ADME
53
Pharmacodynamics
What drug does to body
54
IND
Investigational New Drug
Primary safety doc
submit, if don't hear from FDA 30 days, its a go to do clinical tests
Allows sponsor to legally ship unapproved drug or import from foreign country and between states
Regulatory affairs responsible for initial submission and keeping it updated
55
IND required for...
```
A new chemical entity
New dosage form
New indication
Given and new dosage level
Combo with unapproved drug
```
56
IND contents
Administrative
CMC
Nonclinical
Clinical
57
IND Review includes
Pharmacology, Chemistry, Clinical reviews
58
Phase I
Human pharmacology
small, health group
primary goal to determine tolerability of dose and safety
59
Phase II
Therapeutic Exploratory
Larger group, more narrow criteria
Primary goal to explore efficacy, dose and regimen
60
Phase III
Therapeutic Confirmatory
Confirm evidence from Phase II that drug is safe, effective for use in population.
Primary goal to confirm therapeutic benefit
61
Phase IV
not necessary for approval, good for optimizing the drug.
info on drug-drug interactions, dose-respond, and safety
62
New Drug application
NDA
Goals:
is drug safe and effective
is labeling appropriate
are manufacturing and controls adequate
63
Action following review
Refuse to file = need more info
will send complete response letter notifying of deficiencies
can resubmit, withdraw or appeal application
64
Review types
Standard
non-priority app, ~10 months, not much better than current treatment
Priority
~ 6 months, if no alternate therapy exists or way better than current option
65
Drug app classifications
```
NDA 505(b)(1) contains full report
NDA 505(b)(2) contains report where some info from third party or don't have right of reference
ANDA 505(j) shows product is identical to already approved product
```
66
Reasons to compound
```
Patient allergies
Varying Strengths
Patient compliance
Stability
Medication Discontinued
Veterninary
```
67
Info included in USP <795>
```
compounding records and documents
ingredient selection/calc
how to assign BUD
Quality control
Patient counseling
```
68
USP container classifications
Well-closed: no solids in/out
Tight container: no liquids in/out
Light-resistant container
Hermetic container: no air or gaseous agents can get through, IV ampules....have to break it, sterility depends on this type of container
69
Plastic container Pro vs Cons
```
Pros
o Lightweight
o Durable
o Flexible
o Very “designable”
Cons
o Chemical reactions
o Alteration of properties
o Permeation
o Leaching
o Sorption (adsorption and absorption)
```
70
Permeation
penetration of gases or fluids ie nitroglycerin evaporates
71
Leaching
something from container comes into formulation
72
Adsorption
drug sticks to container
73
Absorption
drug goes into container
74
Polyethylene
HDPE and LDPE
Good water, poor gas barrier
no autoclave
75
Polypropylene
excellent water and gas barrier
| can autoclabe
76
Polyvinyl Chlorine
PVC
used in parenteral, good oxygen barrier, permeable to water
yellows when exposed to heat
77
Info on label
```
NDC
Lot #/ Exp date
Storage info
Strength
dosage form
Name of drug
RX symbol
Quantity in package
Name and location of manufacturer
```
78
OTC labeling
Labeling box
Active ingredient, purpose, warnings, directions, questions, uses, other info, inactive ingredients
79
Storage temps
```
Freezer -25 to -10 c
Cold up to 8 c
Refrigerator 2 to 8 c
Cool 8 to 15
controlled room temp 20 to 25 c, can dip to 15-30, average has to be 25
warm 30 to 40 c
excessive heat 40c+
```
80
Considerations Dosage form Design
```
Effectiveness
Safety
Reliability
Stability
Pharmaceutical Elegance
Physiological State of patient
Convenience
```
81
Preformulation studies
Done before clinical trials to reveal...
| Chemical, Physical, Biological properties
82
Example Preformulation Studies
```
Particle size (mircroscopy, DLS)
Melting point (DSC)
Crystal Structure (microscopy)
Solubility (Solubility test)
Dissolution Rate (Diss tests)
Membrane Permeabiloty (Part. Coeff EIST)
```
83
Stability Preformulation Studies
Stability tests
Shelf Life estimation
Excipients
Mechanisms of Degradation
84
Physical and chemical properties of drugs affected by particle size distribution
Reducing size = increase surface area = more solvent contact = increase solubiltiy
If reduce too much, can be irritant
if too big, cant diffuse across membrane
texture, don't want to by gritty or abrasive ointment
uneven size = settling, stratification (ex miralax)
85
Crystalline solid
repetitive arrangements in a lattice (set structure)
stronger, dissolve slower
temperatures, solutes, solvents impacts which form it takes
Ionic vs molecular solid (ionic stronger)
```
Solvate = solvent trapped in crystal
Hydrate = water trapped in crystal
```
86
Amorphous solid
disordered arrangements of molecules, no structure
easier soluble
drugs can exist in both crystalline and amorphous form ie insulin (crystal = long lasting) intermediate = amorphous
87
Polymorphism
More than one crystal form of a drug
example: Ritonavir (go from one form to another, insoluble)
melting point variation, solubility differences
88
Melting point depression
When peaks vanish or appear somewhere else means drug and excipient are not compatible. DSC used to check compatibility
89
Phase Diagram
Eutectic Point where melting points for combined products meets on graph.
90
Solubility
pH can be adjusted to enhance solubility
not all drugs can benefit from pH adjustments, in which case you can...
use co-solvents,micronization,dispersion, emulsion
91
Dissolution
process by which a particle dissolves
can be rate limiting step in absorption of poorly soluble drugs.
reduce particle size can increase dissolution
speed at which drug dissolves is dissolution rate, tested in dissolution apparatus
92
Membrane permeability
everted intestinal sac test, take rate intestine and test
or do partition coefficient, kind ratio of molecule in octane and water, sweet spot is around 3-5
93
Drug stability
chemical mechanisms of degradation
| Hydrolysis and oxidation
94
Stability testing
done at each stage of product development
temp and humidity studies
have to do for years
95
Type 1 glass
Neutral glass
alkaline element largely eliminated using boric oxide, neutralize oxides of potassium and sodium
suitable for all types of products
96
Type 2 glass
surface treated glass
treat soda glass with sulphur dioxide, ammonium sulphate or ammonium chloride
not good for solution above 8 pH
97
Type 3 glass
soda or alkali glass
less chemically resistant
suitable for dry substances
98
accelerated stability studies
done at exaggerated studies, used to predict how long on shelf. doesn't replace real studies, still have to do those.
exaggerated temp, light and humidity
99
DEA number check
First letter, A or B
Second letter first initial last name or business name.
Add 1,3,5
Add 2,4,6 and multiple by 2
Add both sums, last digit will be 7th DEA number
100
shelf life
time for 10% of drug to degrade, to equal 90% intact drug remaining.
101
shelf life
time for 10% of drug to degrade, to equal 90% intact drug remaining.
102
Pharmacist responsibility
Comply Expiration date
proper storage conditions at pharmacy and educate patients
check for instability
properly treat and label products
103
Pharmacist responsibility
Comply Expiration date
proper storage conditions at pharmacy and educate patients
check for instability
properly treat and label products
104
Shelf life manufacturing vs compounding
```
Manufacturing = 2 years
Compounding = follow USP 795
```
BUD = Beyond Use Date
