Pharmaceutics I Midterm #2 [concepts]

Drug

an agent indended for use in the diagnosis, treatment, cure, or prevention of disease in humans or other animals

What are different classes of drugs based on?

their intended action

When + where was the first pharmacopeia used?

1580 in Bergamo, Italy

What were the three pharmacopeias used in Great Britain?

london, edinburgh, dublin

When did Great Britain merge their three pharmacopeias to form the BP (British Pharmacopeia)?

1864

When was the first USP published in the United States?

1820

What was the first American Pharmacopeia called?

Lititz Pharmacopeia - 1778 in Lititz, PA

Who was Lititz Pharmacopeia used by?

the military hospital

Who is considered the father of the US Pharmacopeia?

Lyman Spalding

What year did a physician from NYC submit a plan to the Medical Society of County of New York to create a national pharmacopeia?

1817

By what year was the USP nearly solely in the hands of the pharmacists?

1870

What did the third revision of the USP (1852) includew?

only the drugs of established therapeutic merit

What did the American Pharmacy Association (APhA) do as a protest for many drugs being excluded from the USP?

prepared a formulary containing many other drugs

When was the first of National Formulary of Unofficial Preparations published?

1888

What the National Formulary of Unofficial Preparations change its name to?

national formulary

What did President Roosevelt do when signed the Food + Drug Act in 1906?

established USP + NF as legal standards

What year did the USP purchase the NF + become the USP/NF?

1975

What does the USP contain?

monographs of drug substances, dietary supplements, dosage forms, + compounded preparations

What does the NF contain?

monographs for pharmaceutical excipients

USP Chapter <795>

pharmaceutical compounding - nonsterile preperations

USP Chapter <797>

Pharmaceutical Compounding - Sterile Preparations

USP Chapter <800>

hazardous drugs - handling in health care settings

USP <1160>

pharmaceutical calculations in pharmacy practice

USP <1163>

quality assurance in pharmaceutical compounding

What does the Food, Drug, + Cosmetic Act require?

a new drug to be approved to legally introduce in the interstate commerce

What does the FDA apply to?

drugs manufactured domestically + those imported

What does drug approval demonstrate?

evidence of safety + efficacy

What does drug approval validate + control?

processes in producing the drug substance, manufacturing, packaging + labeling

What does drug approval ensure?

the product meets established standards of quality

How long is the clinical phase of New Drug Development on average?

6.5 years

What occurs during preclinical research + development?

initial synthesis + characterization

When does short-term animal testing occur?

preclinical into clinical

When does long-term animal testing occur?

late in preclinical into clinical

When does the FDA 30-day safety review occur?

tail end of preclinical research + development

How long is clinical research + development on average?

7 years

When is the New Drug Application submitted?

end of clinical r + d

How does NDA Review + approval take on average?

1.5 years

What happens during postmarketing + surveillance?

adverse reaction reporting, surveys/sample testing, + inspections

How long, on average, does a new drug take from initial synthesis to approval of NDA?

approx. 15 years

What are the sources of new drugs? (5)

isolation from plants, extraction from animals (tissues), molecular modification, organic synthesis, genetic engineering

What are the types of genetic engineering? (3)

recombinant DNA (rDNA) tech, monoclonal antibody (mAb) production, human gene therapy

What can rDNA technology do?

produce almost any protein, genetic transplantation from higher → lower species to produce a protein it doesn’t normally

What is the purpose of mAb production?

mAb production is entirely within the cells of higher animals, antibodies bond to specific target

What is human gene therapy used for?

to prevent, treat, cure, diagnose, or mitigate human diseases caused by genetic disorders through the transfer of new genetic material to the cells of a patient with a genetic disease

What are the methods of discovery? (4)

random or non-targeted screening + non-random or targeted screening, bio-assays, molecular modification, mechanism-based drugh design

Random or Non-Targeted Screening and Non-Random or Targeted Screening

the testing of large numbers of synthetic organic compounds or substances of natural origin for biologic activity

Bio-Assays

to differentiate the effect + potency (strength of effect) of the test agent from those of controls of known action + affect; in vitro cell culture

Molecular Modification

a chemical alteration of known organic compound to enhance its usefulness as a drug

What are reasons for molecular modifications? (6)

to increase the specificity for a particular body target site, increase its potency, improve its rate + extent of absorption, modify to advantage its time course in the body, reduce its toxicity, or change its physical or chemical properties (ex: solubility)

What does drug metabolism result in?

the production of one or more metabolites of the administered drug

What occurs fter sufficient chemical + physical characterization?

initial formulations of the dosage form are developed for human CTs

What are the pre-formation studies? (5)

drug solubility, partition coefficient, dissolution rate, physical form, + stability

What is the purpose of a solubility pre-formation study?

to achieve desired drug concentration in the systemi circulation

What are considered solubility enhancements?

salts, esters, chemical complexation, reduction in particle size

What is the purpose of a partition coefficient pre-formulation study?

to measure of a drugs distribution in a lipophilic-hydrophilic phase system

Dissolution Rate

the speed at which the drug dissolves in a medium

What forms can affect the dissolution rate?

acid, base, or salt

What does a reduced particle size/increased powder fineness lead to?

increased surface area → higher dissolution rate → higher absorbtion

What is looked at in stabilty studies?

antioxidants, moisture protection, light protection, packaging

What are the FDA’s obectives in reviewing an IND?

to protect the afety + rights of the human subjects

CDEF

center for drug evaluation + research

CBER

center fr biologics evaluation + research

FDA Class Type 1 (by chemical type)

new molecular entity; not marketed in US

FDA Class Type 2 (by chemical type)

new ester, salt, or other derivative of an approved active moiety

FDA Class Type 3 (by chemical type)

new formulation of a drug marketed in US

FDA Class Type 4 (by chemical type)

new combination of 2+ compounds

FDA Class Type 5 (by chemical type)

new manufacturer of a drug marketed in the US

FDA Class type 6 (by chemical type)

new therapeutic indication for an approved drug

FDA Class Type P (by therapeutic classification)

priority review; a new therapeutic gain

FDA Class Type S (by therapeutic classificaiton)

standard review; similar to other approved drugs

FDA Class Type AA (additional classifications)

for treatment of AIDS or HIV-related disease

FDA Class Type E (additional classifications)

for life-threatening or severely debilitating disease

FDA Class Type F (additional classifications)

review deferred pending data validation

FDA Class Type G (additional classifications)

data validated; removal of F rating

FDA Class Type N (additional classifications)

nonprescription drug

FDA Class Type V (additional classification)

drug having orphan drug status

What is the purpose of Phase 1 testing?

mainly safety

How many patients are used in Phase 1 testing?

20-100

What % of drugs were successfully during Phase 1?

70%

What is the purpose of Phase 2 testing?

some short-term safety but mainly effectiveness

How long does Phase 1 testing take?

up to 1 year

How many patients are there in Phase 2 testing?

100 - 500

How long does Phase 2 testing take?

several months to 2 years

What % of drugs successfully tested during Phase 2?

33%

What is the purpose of Phase 3 testing?

some short-term safety but mainly effectiveness

How many patients are in Phase 3?

1000 - 5000

How long does Phase 3 testing take?

1-4 years

What % of drugs successfully tested during Phase 3?

25-30%

Pharmaceutics

a core discipline of pharmacy which deals with turning an active pharmaceutical ingredient (API) into a medication for safe + effective use by patients for therapeutic benefits

What does pharmaceutics deal with?

formulation, manufacturing, stability, + effectiveness of a dosage form

Pharmaceutical Formulations

the process of devising a recipe or formula for a dosageform

What do pharmaceutical formations contain?

one or more active ingredient (drug) + many additives depending on the dosage forms called excipients

Routes of Administration

route of drug administration refers to the path by which a drug is taken into the body, usually classified by location at which the drug is applied

Polymorphism

the ability of a substance to crystallize in 2+ different crystal forms, each of them having the same chemical structure but different conformations in the crystal lattice

What is dissolution rate often the rate limiting step in?

the absorption of a poorly soluble drug

Partition Coefficient

the measure of a drug’s lipophilicity + an indication of its ability to cross cell membranes

Partition (P) or Distribution Coefficient (D)

the ratio of concentration of a compound in the two pases of a mixture of two immiscible solvents at equilibrium

Partition Coefficient (LogP)

the ratio of concentrations of an unionized compound between an aqueous + organic solvent measured by adjusting the pH so that compound remains predominantly in the unionized form in the solvent

What is a drug classifiedas when P is greater vs less than 1?

lipophilic vs hydrophilic