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159 Cards in this Set
- Front
- Back
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A new drug application will have all of the following in it EXCEPT
a) human pharmacokinetics b) bioavailability c) microbiology (for anibxs) d) pictures of the medication e) benefits/risk discussion for drug usage f) proposed product labeling (including dosage) |
d.
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A new drug application intergrates all data on the drug and is
a) typically 100 pages or more & takes 6 months to review b) typically 10,000 pages or more & takes 2 years to review c) typically 10,000 pages or more & takes 1 year to review d) typically 5000 pages or more & takes 1 year to review |
c) typically 10K pages or more & takes 1 year to review (on average)
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Prior to final approval of a NDA, the manufacturing facilities must be inspected to assure its capability to comply with quality standards including
a) what's contained in the application b) what's specified in the FDA's Critically Good Manufacturing Procedural Standards c) what's specified in the FDA's Current Good Manufacturing Practice Standards d) a & b e) a & c |
e) a & c
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T/F? In the decision process of a NDA, the approval letter further conditions that must be met for approval & decribes what deficiencies must be corrected.
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false
(the APPROVABLE letter does this) more info: (1) Approvable letter (2) Approval letter (3) Not Approvable letter--application has 1+ significant deficiencies |
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T/F? As of this past August, the FDA now has a 2 choice decision process--one of approval or one where they will issue a "complete response" letter in detail actions to take to get approved.
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true
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In the post-marketing phase of an approved drug,
a) Phase 4--Clinical studies req's the drug product is continually monitored in clinical investigations to add to the understanding of the drug's effects.the drug product is continually monitored in clinical investigations to add to the understanding of the drug's effects. b) adverse rxn reporting must be made & the drug's sponsor is req'd to review and report to the FDA all adverse effects reported to them by any internal or external sources (e.g. physicians, postmarketing studies, RPh's, etc) c) comprehensive annual reports are req'd d) all of the above |
d) all of the above
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An orphan disease is a disease that
a) is rare & affects fewer than 500,000 people in the US b) is rare & affects fewer than 200,000 people in the US c) there's no reasonable expectation that costs of research and development for the indication can be recovered by sales of the product in the US c) a & c d) b & c |
d) b & c
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Examples of orphan diseases include
a) cystic fibrosis b) multiple sclerosis c) chronic lymphocyte leukemia d) a & b only e) a & c only f) all of the above |
e) a & c only
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The purpose(s) of IND for orphan drugs include
a) to develop drugs where there is an insufficient market incentive b) financial support for clinical trials c) 7 yrs of exclusive marketing rights d) a & b only e) all of the above |
e) all of the above
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In the treatment of IND, a "treatment protocol"
a) is filed during phase 1 and 2 to allow treatment of the desperately ill b) is filed during phase 2 and 3 to allow treatment of the desperately ill c) is filed during phase 1-4 to allow treatment of the desperately ill d) is filed during phase 2 only to allow treatment of the desperately ill |
a) is filed during phase 1 and 2 to allow treatment of the desperately ill
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An Abbreviated New Drug Application omits nonclinical lab studies and clinical studies except those pertaining to
a) pharmacokinetics b) bioavailability c) microbiology d) toxicology |
b) bioavailability
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T/F? Generic drugs get on the market by an Abbreviated NDA.
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true
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A Supplemental New Drug Application is used if there are changes in all of these EXCEPT
a) drug formulation or synthesis b) manufacturing facilities c) analytical standards d) container e) all of these are correct |
e) all of these are correct
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T/F? Preclinical research and development (R&D) takes about 1 year.
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false (about 2 years)
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T/F? Phase 1 takes about 3 years.
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true
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T/F? Phase 3 takes about 5 years.
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true
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T/F? NDA submission takes about 5 years.
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false (about 8 years)
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The extent to which a (drug) product retains, within specified limits, and throughout its period of storage and
use (i.e., its shelf-life), the same properties and characteristics that it possessed at the time of its manufacture is called a) drug integrity b) drug toxicology c) drug pharmacokinetics d) drug stability |
d) drug stability
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A property that is relevant and critical to the stability of a drug is its ________ ________ and means that a drug must stay intact.
a) chemical stability b) physical stability c) chemical integrity d) physical integrity |
c) chemical integrity
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Changes in chemical stability of a drug can effect all of the following EXCEPT:
a) therapeutics b) toxicology c) organoleptic properties d) all of the above are true |
d) all of the above are true
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Examples of chemical therapeutic changes include
a) pharmacology b) kinetics c) blood levels changing d) a & b e) all of the above |
d) a & b
(blood level changes is an example of a PHYSICAL therapeutic change) |
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T/F? During clinical studies, the final formulation is completed as well as the packaging and labeling.
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True
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What is the term used that describes 1 to 2 molecules that differ only in the spatial arrangment around a single carbon atom?
a) organoleptic b) epimerize c) propagation d) isomerize |
b) epimerize
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Penicillins can decompose in ______ solutions to possibly ________ compounds.
a) acidic, toxic b) basic, toxic c) acidic, allergenic d) basic, allergenic |
c) acidic, allergenic
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__________ can degrade under ________ conditions yielding _________ as a byproduct & causes respiratory depression.
a) Tetracycline, acidic, uric acid b) Pilocarpine, basic, cyanide c) Paroxetine, acidic, cyanide d) Pralidoxime, basic, cyanide |
d) Pralidoxime, basic, cyanide
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_________ properties are susceptible to sensory impressions.
a) Sympathetic b) Aromatic c) Organoleptic d) Elegant |
c) Organoleptic
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Not only is chemical integrity critical for drug stability, physical integrity is also. Changes in physical integrity can affect
a) toxicity b) therapeutics c) organoleptic properties d) a & b e) b & c f) a, b & c |
e) b & c
(toxicity is only mentioned under chemical integrity) |
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An example of therapeutic changes with physical integrity include
a) pharmacology b) kinetics c) blood levels d) all of the above |
c) blood level changes
(due to dissolution changes/solubility) |
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And example of an organoleptic property change is
a) dissolution in suspensions b) dissolution in solutions c) dissolution in powders d) all of the above |
a) dissolution in suspensions
(drig in soln elicits taste) |
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T/F? Microbial invasion of a drug product is considered a stability problem.
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true
(can be unappealing and/or deadly) |
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The most common degradation mechanisms are hydrolysis (#1 most common) & oxidation, but other degradation mechanisms include
a) photolysis b) dehydration c) isomerization d) polymerization e) a, b, & c only f) all of the above |
f) all of the above
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Examples of functional groups susceptible for hydrolytic cleavage include all of the following except
a) esters b) amides c) phenols d) lactams e) lactones |
c) phenols
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An example of an ester that's susceptible to hydrolytic cleavage is
a) penicillin b) aspirin c) spironolactone d) dibucaine e) captopril |
b) aspirin
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Degradation products of ester hydrolysis include
a) carboxyl b) alcohol c) quinone d) a & b e) a & c |
d) a & b
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Degradation products of Amide hydrolysis include
a) carboxylic acid b) amine c) alcohol d) a & b c) a & c |
d) a & b
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An example of a lactam (cyclic amide) that's susceptible to hydrolytic cleavage include
a) penicillins b) cephalosporins c) spironolactones d) catecholamine e) a & b f) none of the above |
e) a & b
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An example of a lactone (cyclic ester) that's susceptible to hydrolytic cleavage includes
a) penicillin b) spironolactone c) catecholamine d) aspirin |
b) spironolactone
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T/f? Lactone is also known as a cyclic amide.
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False (aka cyclic ESTER)
cyclic amide is Lactam |
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Removal of electrons is known as
a) hydrolysis b) oxidation c) polymerization d) ionization |
b) oxidation
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T/F? Autoregulation is a fast process because oxygen is very reactive, removing electrons quickly.
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false
(it's SLOW b/c O2 is NOT very reactive & CAN'T remove electrons) |
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A type of oxidation that involves the uncatalyzed oxidation of a substrate by molecular oxygen is called
a) autoxidation b) autoregulation c) free radial oxidation d) deoxidation |
a) autoxidation
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T/F? Molecular oxygen (O2) is a double diradical (designated 2O2) and has 2 unpaired electrons with parallel spins.
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false
(it's a TRIPLET diradical (3O2)...) |
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Molecular oxygen is not very reactive compared to some reactive oxygen species such as
a) superoxide b) hydrogen peroxide c) hydroxyl radical d) oxidative radical e) a, b & c f) all of the above |
e) a, b & c
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Free radical mechanism of oxidation involve
a) initiation b) propogation c) termination d) radicalization e) a & b only f) a, b & c |
f) a, b & c
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__________ involves the formation of substrate free radicals necessary for the propagation of the chain.
a) Initiation b) Propogation c) Termination d) all of the above |
a) Initation
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Which of the following is FALSE involving initiation in oxidation?
a) involves hydrogen abstraction b) can occur through autoxidation by molecular oxygen or w/ other chain-initiating radicals c) free radicals combine to form chemically inert products d) chain initiating radicals are generated by the action of light, heat, transition metals, or reactive compounds |
c) free radicals combine to form chemically inert products
(this defines TERMINATION) |
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__________ in the free radical mechanism of oxidation happens when free radicals grow in number
a) Initiation b) Propogation c) Termination e) Isomerization d) none of the above |
b) Propogation
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__________ in the free radical mechanism of oxidation happens when free radicals combine to form chemically inert products
a) Initiation b) Propogation c) Termination d) all of the above |
c) Termination
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Functional groups susceptible to oxidation include all of the following except
a) amides b) phenols c) cetechols d) thiols e) polyunsaturated hydrocarbons |
a) amides
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A drug example for the oxidation susceptible functional group catechols include
a) captopril b) catecholamine c) spironolactone d) morphine e) a, b & c |
b) catecholamine
note: epinephrine is import to catechols, also. -catechols produce quinones, which are usually colored |
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A drug example for the oxidation susceptible functional group thiols include
a) captopril b) catecholamine c) spironolactone d) morphine e) a, b & c |
a) captopril
note: captopril forms a dimer -cysteine is found in proteins -thiols form disulfide bonds when oxidized |
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Examples of polyunsaturated hydrocarbons include
a) carbohydrates b) lipids c) Vitamin E d) Vitamin A e) b & c f) b & d |
f) b & d
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__________ is the chemical breakdown caused by light that usually involves complex mechanisms.
a) Photosynthesis b) Ozonolysis c) Photolysis d) Isomerization |
c) Photolysis
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All of the following describes photolysis EXCEPTL
a) a photon with a wavelength of 300nm has 200kJ/mol of energy comparable to bond energy of organic molecules, thus helping to break or make bonds. b) different molecules have susceptibilities to different types of light based on their absorption characteristics c) The most common photolytic mechanism is photoxidation d) all the above are true |
a.
(300nm has 400kJ/mol of energy, not 200) |
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The most common photolytic mechanism is
a) photohydrolysis b) photodehydration c) photoxidation d) photoisomerization |
c) photoxidation
(a & b are all kinds of photodegradation rxns that can occur) |
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Besides hydrolysis, oxidation, and photolysis, some other chemical degradations include
a) dehydration b) isomerization c) polymerization d) a & b only e) all of the above |
e) all of the above
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T/F? Dehydration is considered a physical process when looking at the elimination of water molecules from the chemical stucture.
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false
(it's a chemical process) physical=removal of H2O froma crystal hydrate, which is a type of polymorphism |
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An example of dehydration degradation in medicine include
a) penicillins b) erythromycin c) tetracycline d) macrolides e) a, b, & c f) b & c only |
f) b & c only
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T/F? Physical dehydration does not change solubility of a drug
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false
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Isomerization degradation involves all of the following except
a) conversion of a drug to its enantiomer or geometric isomer b) stereoisomerism involving the arrangement of substituents about an symetric carbon atom(s) so that the various isomers differ in how they rotate a plane in polarized light c) examples include pilocarpine, epinephrine, penicillin, Vitamin E, and amphotericin A d) all of the above are correct e) all of the above are false |
e) all of the above are false
corrected versions: a) conversion of a drug to its OPTICAL or geometric isomer b) stereoisomerism involving the arrangement of substituents about an ASSYMETRIC carbon atom(s) so that the various isomers differ in how they rotate a plane in polarized light c) examples include pilocarpine, epinephrine, tetracycline (not penicillin!), Vitamin A (not E!), and amphotericin B (not A!) |
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All of the following are significant to isomerization except
a) Geometric isomers are the same in their physicochemical properties b) It's estimated that 50-60% of drugs are chiral compounds, with most of them being racemic mixtures c) Enantiomers can have different biological properties d) Drugs marketed as a pure enantiomer may racemize |
a)
Geometric isomers can DIFFER in their physiochemical properties |
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What drug can undergo base-catalyzed racemization in aqueous media?
a) ampicillin b) chlorpromazine c) pilocarpine d) thalidomide e) all of the above |
d) thalidomide
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_________ are a pair of molecular entities which are mirror images of each other and non-superimposable.
a) Constitutional isomers b) Stereoisomers c) Enantiomers d) Polymers |
c) Enantiomers
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What is the term used to describe when 2 or more drug molecules combine to form a complex molecule?
a) Isomerization b) Polymorphism c) Polymerization d) Racemization |
c) Polymerization
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Medication examples of polymerizations include all of the following except
a) ampicillin b) tetracycline c) chlorpromazine d) aminopenicillins |
b) tetracycline
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Physical degradation mechanisms that change physical properties rather than chemical structure include all of the following EXCEPT
a) polymorphism b) hygroscopicity/water sorption c) vaporization d) absorption to containers e) all of the above are correct |
d)
correct: adsorption to containers |
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____________ is the capacity for appearing in many forms.
a) Polmerization b) Hygroscopicity c) Amorphism d) Polymorphism |
d) Polymorphism
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Regarding polymorphism, what are some possible forms of a solid drug?
a) cystalline form b) amorphous form c) pseudomorphous form d) a & b only e) all of the above |
d) a & b only
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__________ form has repeating/periodic arrangement of the individual molecules that creates a crystal lattice.
a) Amorphous b) Pseudomorphous c) Crystalline d) Semi-polymorphous |
c) Crystalline
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The internal structure and habits of the cystalline form of a polymorphic solid drug include
a) different molecular arrangement are possible with a solid. b) a particular arrangement defines the internal structure c) the external structure determines the crystal habit d) a & b only e) all of the above |
d) a & b only
c is false because it should say "the INTERNAL structure determines the crystal habit" |
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Regarding the crystalline form, what is the chemistry term that describes the outer appearance of a crystal?
a) habit b) suit c) prism d) container |
a) habit
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T/F? Different habits can result from only major changes in synthetic conditions.
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false
from MINOR changes |
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Examples of crystalline habits include
a) needle b) bladed c) tabular d) prismatic e) platy f) all of the above |
f) all of the above
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A drug example of a crystalline form includes
a) ampicillin b) pralidoxime c) carbamazepine d) alprazolam |
c) carbamazepine
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_________ form means without distinct structure & has no repeating/periodic arrangement.
a) Pseudomorphous b) Polymorphous c) Crystalline d) Amorphous |
d) Amorphous
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Regarding the importance of the solid state, the form of a solid may affect all of the following except
a) flow properties b) efflorescence properties c) mechanical properties (compaction) d) bioavailability e) melting point f) solid state stability |
b) efflorescence properties
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What's important for dosage uniformity?
a) flow properties b) mechanical properties c) bioavailability d) melting point e) solid state stability |
a) flow properties
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What's a function of drug dissolution, changes with different drug forms, and is a fraction of an administered dose that reaches the systemic circulation?
a) flow properties b) mechanical properties c) bioavailability d) melting point e) solid state stability |
c) bioavailability
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What is a function of strength of molecular interactions?
a) flow properties b) mechanical properties c) bioavailability d) melting point e) solid state stability |
d) melting point
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Examples of this is hyperscopicity (uptake of H2O onto a solid dose form) and polymorphism (changes in form).
a) flow properties b) mechanical properties c) bioavailability d) melting point e) solid state stability |
e) solid state stability
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T/F? Depending on crystallization conditions, some drug solids may have at least three different molecular arrangments, each giving distinct crystalline species, or polymorphs.
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false
...at least two different molecular arrangements... |
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Important features of polymorphs include all of the following except
a) polymorph solubility b) polymorph stability c) polymorph conduction d) polymorph interconversion |
c) polymorph conduction
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T/F? Regarding polymorph solubility, metastable polymorphs are generally less soluble than their more stable counterparts.
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false
...MORE soluble... |
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__________ polymorphs means they're approaching stability b/c of weak interactions, and an example of this (drug) is __________.
a) pseudostable, chlorpromazine b) metastable, chlorpromazine c) metastable, chloromycetin d) metastable, chloramphenicol |
d) metastable, chloramphenicol
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Chloramphenicol palmitate has ___ polymorphs, ___ is more soluble in a mixture, and it has to be in molecular form in order to cross membranes.
a) 2, B b) 3, B c) 3, A d) 2, A |
b) 3, B
B was more soluble in a mixture of A & B in suspension. |
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T/F? If a drug stays in suspension, it wont pass thru a membrane.
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true
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T/F? The molecules within different polymorphs interact the same.
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false
they interact differently |
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All of the following is true regarding polymorph stability except
a) when molecules with weaker molecular interactions are metastable b)they're in an unstable and transient but relatively long-lived state of chemical or physical system c) they may change over time to a less stable form d) amorphous solids are metastable, are great for solubility, but aren't stable b/c they change to crystalline form |
c)
correct: they may change over time to a MORE stable form |
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When can polymorph interconversion occur?
a) during processing b) during grinding c) during drying d) during exposure to high humidity e) sitting on the shelf f) all of the above |
f) all of the above
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Some drug examples of polymorph interconversion include ________ (grinding crystals of this drug can lead to an amorphous form & increase conc. in blood) and _________ (which has 8 potential polymorphs that can interconvert in suspension).
a) cortisone acetate crystals in susp., digoxin b) chloramphenicol palmitate, cortisone acetate cystals in susp. c) digoxin, cortisone acetate crystals in susp. d) digoxin, chloramphenicol palmitate |
c) digoxin, cortisone acetate crystals in susp.
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Regarding polymorph interconversion, which of the following is FALSE for cortisone acetate crystals in suspension?
a) has 9 potential polymorphs b) may cause some suspended drug to dissolve c) increases degradation rate d) crystals can become bigger and cause settling |
a)
correct: has 8 potential polymorphs |
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What's the term used when you have drug crystallize as a combination of pure drug & the solvent of crystallization?
a) solvent b) solvate c) amorphic d) none of the above |
b) solvate
aka "hydrate" b/c water is part of the crystal lattice note: this is an example of of "pseudopolymorphism" of solvates |
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Regarding "pseudopolymorphism" of solvates, Theophylline has ____ H20 molecules for every ____ theophylline molecules.
a) 5, 5 b) 5, 6 c) 6, 6 d) 6, 5 |
c) 6, 6
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All of the following are true regarding solvate stability EXCEPT
a) solvates can be physically unstable under certain conditions b) efflorescence can occur when there's a release of H2O of hydration from a crystal hydrate c) some hydrates can lose H2O-of-hydration during handling, like grinding d) solvates can interconvert to different forms during processing, such as grinding |
d)
(this refers to POLYMORPH interconversion) |
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All of the following involves solvate solubility except:
a) changes in hydrate form can affect solubility b) because of the energetics of dissolution, hydrates are generally more soluble than their anhydrous counterparts c) a good example, ampicillin, can be given in anhydrous or trihydrate form showing anhydrous dissolves better d) all of the above are true |
b)
corrected: because of the energetics of dissolution, hydrates are generally LESS soluble than their anhydrous counterparts |
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The tendency of a substance to take up atmospheric moisture is called
a) vaporization b) adsorption c) polymorphism d) hygroscopicity |
d) hygroscopicity
(aka water sorption) |
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In the manufacturing and handling of drugs, increased cohesiveness can lead to
a) poor flow and mixing of powders b) caking of powders c) deliquescence d) a & b e) a, b, & c |
e) a, b, & c
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The dissolution of a solid upon uptake of atmospheric moisture is called
a) deliquescence b) efflorescence c) elegance d) hydroscopicity |
a) deliquescence
remember: hydroscopicity is just the tendency of a substance to take up atmospheric moisture |
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Regarding hygroscopicity, preformulation studies include ________ the solid by storing at _____ humidity.
a) stressing, low b) disrupting, low c) stressing, high d) disrupting, high |
c) stressing, high
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Drugs are generally more stable in the solid state, however the uptake of water by the solid drug can accelerate the drug's _________ degradation, and an example (drug) includes
a) chemical, aspirin b) chemical, penicillin c) physical, aspirin d) physical penicillin |
a) chemical, aspirin
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T/F? Drugs and excipients with low vapor pressure may volatilize through or within the container.
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false
...with HIGH vapor P... |
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Some examples of drugs and excipients with high vapor P's tha may volatilize through a container include all of the following EXCEPT
a) flavorants b) cosolvents c) kelators d) nitroglycerin |
c) kelators
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A ________ is a solvent used in combination with another solvent to increase solute's stability.
a) cofactor b) cosolvent c) kelator d) buffer |
b) cosolvent
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Certain drugs, especially within solution, can _______ to their container or other devices they come in contact with
a) permeate b) absorb c) kelate d) adsorb |
d) adsorb
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Drug-container interax such as drug-plastic interax in IV admixtures usually involve lipid soluble drugs such as
a) diazepam b) insulin c) isosorbide dinitrate d) a & b a) all of the above |
a) all of the above
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Preformulation/formulation has to do with
a) stability b) incompatibility c) absorption d) dissolution e) a, b & d only f) all of the above |
e) a, b & d only
(absorption has to do with biocharmaceutics) |
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Biopharmaceutics has to do with all of the following except
a) absorption b) stability c) distribution d) elimination e) pharmacokinetics |
b) stability
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When looking at chemical kinetics, the instantaneous rate (velocity/speed) of a reaction is given by the change in ____________ of the species over _____________.
a) time, concentration b) velocity, time c) concentration, time d) speed, concentration |
c) concentration, time
rate=C/t |
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In the reaction rate equation rate=k[A^a][B^b] (k has a sub (a+b)), k is called the ______ ________ of the reaction at a particular ___________.
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rate constant
temperature (a & b are the # of mole equivalents of each reactant A & B) |
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The overall order of the reaction (n) may be defined as ________.
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n=a+b
(sum of the exponents) note: the order of a rxn may also be denoted with respect to each reactant |
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For pharmaceutics, ____, ____, & ____ order reactions are of greatest interest.
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zero, first, & second
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In first-order degradation, the degradation rate varies as the first power of the concentration of the _________ and is __________ of the concentration of any other substance that may be present.
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substrate
independent -dC/dT=kC^1 note: units of k are reciprical time |
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For first-order rxns, ________ is proportional to _________ & there's exponential decay.
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rate
concentration |
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When looking at a plot of ln C vs t, what's the intercept and what's the slope?
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lnCo=intercept
K1=slope |
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The actual order for most hydrolytic reactions is...
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pseudo first-order degradation
where the degradation rate is apparently independent of the concentration of one of the ractants, even though it's consumed in the rxn. |
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What is an example of a pseudo first-order degradation rxn?
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ester hydrolysis in dilute aqueous soln.
note: since water is in such great excess, its loss is considered negligible (and concentration is considered constant) |
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When the concentration change is described by the equation -dC/dT=kC^o=ko, it's what order
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zero-order
ko is the zero-order rate constant. units for k are concentration per unit time |
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As for first-order degradation, the __________ rate equation for a zero-order rxn enables a calculation of the remaining concentration at any point in time: C = Co - kot
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integrated
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What's the intercept for a zero-order rxn?
What's the slope for a zero-order? |
Co=intercept
ko=slope |
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Zero-order drug degradation can occur where there is a __________ of drug to replace drug that's lost to decomposition.
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reservoir
note: e.g. some suspensions --conc. as drug is degrading stays CONSTANT b/c there's replacement going on. |
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With knowledge of ___a___ _____ ______ and ___b_____ ______, one can readily estimate the shelf-life of a product using equations derived from the ____c____ ____ _________.
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a) rate constant values
b) reaction order c) integrated rate equations |
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Most often, the shelf-life is defined as the time for ____ degradation (denoted as ___).
a) 5%, t95 b) 10%, t90 c) 20%, t80 d) 50%, t50 |
b) 10%, t90
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Regarding pH, ______ and ______ can catalyze rxns.
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proton, hydroxyl ions
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In ____ ______, protonation of the carbonyl oxygen makes the carbon more electrophilic.
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acid catalysis
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In ____ _______, the hydroxyl ion is very nucleophilic.
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base catalysis
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During preformulation, ______ ______ are routinely generated for the drug candidate in solution. The profiles have a variety of shapes which indicates different types of _________.
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pH-rate profiles
catalysis |
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The ___________________ can often be estimated from the pH-rate profiles.
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pH of maximum stability
(this is the point where k is lowest) |
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Regarding temperature, typically a ____ rise in temp produces a ____ fold decay rate INCREASE.
a) 5 C, 2-4 fold b) 10 C, 2-4 fold c) 10 C, 2-5 fold d) 20 C, 2-5 fold |
c) 10 C, 2-5 fold
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The ________ ______ can be used to model the effect of temperature on degradation and make useful predictions of the effects of different temperatures on the product's shelf-life.
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Arrhenius equation
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In the Arrhenius equation k=Ae^(Ea/RT), A is the __________,
Ea is the ________, R is the _________, and T is the ___________. |
k=Ae^(Ea/RT)
k=rxn rate constant A=constant called the FREQUENCY FACTOR Ea=energy of activation for the rxn R=gas constant T=absolute temperature |
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In the Arrhenius equation, A is called the ______ _____, which indicates how many ______ have the right orientation to lead to the products.
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frequency factor
collisions |
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When converted to its logarithmic form, the Arrhenius equation is useful for _________ __________ studies.
What's this equation? |
accelerated stability studies
lnk= lnA - Ea/RT (a plot of lnk vs. 1/T yields |
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As long as a plot is linear, the pharmaceutical scientist can determine degradation rates at ____ temperatures and extrapolate to ______ temperatures.
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high
lower (used mainly to predict shelf-life under storage conditions) |
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One approach to accelerated stability testing would be to (1) plot a function of _____a______ vs. ___a___ for a drug solution at elevated temperatures (usually btwn 35 C and 70 C).
(2)Then calculate the rate constant at each temp, from the ___b____. (3)And plot the log of the calculated __c___ ___c___ vs. ___c_____ of the __d___ temperatures. (4)extrapolate to find rate constant at __e__. (5) Using k250, determine __f___. |
a) concentration vs. time
b) from slope c) rate constants vs. reciprocal d) absolute temp e) 25 C (k250) f) shelf-life |
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Examples of non-Arrhenius behavior includes include
a) where temperature changes lead to solvent evaporation b) where temp changes lead to multiple rxn pathways c) where temp changes lead to change in physical form of the preparation d) where freezing the product concentrates the solutes, with untoward consequences. e) all of the above |
e) all of the above
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Frozen ampicillin solution would lead to pockets of high concentration, thus _______ degradation rate.
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increasing
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Frozen buffers in solution would make the buffer crystallization alter ____.
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pH
(degradation is dependent of pH) |
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_______ _____ studies must be performed in the final formulation in the final storage container.
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Accelerated stability studies
(both the formulation and container can affect stability) |
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Though tentative expiration dates can be assigned using accelerated stability studies, there must be long term studies under ___ ____ and _____ ______.
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normal transport & storage conditions
(used to verify & maybe extend the expiration date) |
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If the expiration date includes only the month & year, the product must meet specifications until _____________.
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the last day of the month
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For solid dosage forms, samples are generally stressed by storing at __a__, at high ___b_____ for _c__ to _c__ months.
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a) 40 C
b) high humidities c) 6 to 12 months (to rapidly determine the effect of water sorption--hydroscopicity) |
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To maintain stability, dosage formulation & production approaches include
a) stored at reduced temperatures b) buffer the product appropriately c) dry the product d) a & b only e) all of the above |
e) all of the above
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When storing meds at reduced temps, you must consider what?
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-consider potential problems with freezing
-consider the potential for water condensation |
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When you buffer a product appropriately, you want to do it at the ___ of _____ stability.
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pH of maximum stability
note: must also consider solubility |
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Dry dosage forms include tablets, capsules, and powders, but also includes _______ which are the silica gel packets commonly used to absorb water.
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desiccants
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To make "solvent loving" as in freeze-drying is called ____________.
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lyophilization
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Lyophilization starts with a frozen product. What are the 3 steps to do this?
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1) starts with liquid that includes drug plus excipients
2) the samples are frozen then sublimed under vacuum 3) a porous matrix usually results (pores remain where water crystals were) |
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What are some additional measures used to maintain stability?
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1) remove/replace O2 (distill, then purge the water with an inert gas or fill headspace with an inert gas)
2) Use antioxidants (oil-soluble or water-soluble) 3) use chelators to minimize metal content 4) protect from light |
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An example of an oil-soluble antioxidant would be __________ or ___________.
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alpha-tocopherol (Vit E)
or buylated hydroxytoluene (BHT) |
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An example of water-soluble antioxidant would be _______ or _________.
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ascorbic acid (Vit C)
or sodium sulfite (which is a common allergenic in 0.2% of the population) |
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The two principle mechanisms of antioxidant action are (choose 2 answers):
a) stop propagation b) start propagation c) preferentially oxidized d) preferentially hydrolyzed |
a & c
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To minimize metal content, you would use...
which includes... |
chelators
citric acid, EDTA (ethylene diamine tetraacetic acid) |
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For oral and topical products, no more than __% of the light at any wavelength btwn ____ and ____ may be transmitted.
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10%
290nm and 450nm |
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The lower the wavelength of light, the ________ the energy.
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higher
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What kind of light has high energy and is absorbed by most drugs?
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UV light
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_________ light includes some UV light.
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fluorescent
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To protect medications from light, you can use...
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opaque or amber containers
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What are the responsibilities of a pharmacist (from the USP) in regard to stability?
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1) rotation of stock & observation of expiration dates
2) storage under recommended environmental conditions 3) Observing products for evidence of instability 4) proper treatment of products subject to additional manipulation 5) informing and educating the patient |
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A manufacture guarantees product quality up to the expiration date only if the product...
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has been stored in the original container under recommended storage conditions
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