Dosage form

Objective:

an entity administered to a patient so that they receive an effective dose

Objective: achieve a predictable therapeutic response using a formulation capable for large scale manufacture

applied research designed to optimize physical and chemical properties of drugs in order to improve drug delivery

focus: physical & chemical properties, kinetics, powder technology, tablet compression

how physicochemical properties of drugs, dosage forms, effect rate and extent of absorption

how the drug is absorbed

time course for absorption, distribution, metabolism, and elimination

blood samples are collected

what the body does to the drug

predict drug concentration in blood/plasma or tissue

calculation of dosage regimen

effect of disease on drug disposition

mechanism of D-D I

drug concentration : effect

• comparison of drug concentration at site of action, and pharmacological response

• assumes blood drug concentration reflects drug concentration at target site

• biochemical and physiological effects and mechanism of action

• what the drug does to the body

Absorption

Distribution

Metabolism

Excretion

Elimination

Absorption: movement from site to blood

Distribution: reversible movement of drug from blood to tissue

Metabolism: chemical transformation of the drug

Excretion: physical removal of the drug

Elimination = Metabolism + Excretion 

(at absorption, some elimination is occurring)

the rate and extent that a drug is absorbed and becomes biologically at site of action

drug must be in solution

fraction of the administered dose which is absorbed intact into the systemic circulation

IV drugs have 100% bioavailability

drugs from digestive track pass through hepatic portal system to liver.

some drug lost by gut wall, and by liver

overcome by changing route, or by giving a lot at start like zpack

FDA

CFR

cGLP

DMF

IND

FDA: regulate drugs, diagnostic, and medical devices through out title 21 of the CFR

CFR: US code of federal regulations (also discusses rules for IND)

cGLP: current good laboratory practices: rules made by FDA.

cGMP: current good manufacturing practices.  for making large scale product.

cGCP: current good clinical practice: (FDA) followed by clinical protocols

Toxicology

Pharmacology

Toxicology: eratogenicity: interfering w/ embrio

Pharmacology: what biological system the drug interacts with, how, and what effects.

if the drug does something, it gets an IUPAC.

nonproprietary name: Generic is submitted to the

USAN: US adopted names council

DMF

1

DMF: Drug master file. 

type 1: certification of a site by FDA to do cGMP.

type 2: specific to compound

type 3: packaging

type 4: excipients

type 5: FDA acepted reference info

IND: investigational new drug application.  must be filed before human testing.  describes test plans, MSDS, tests in other countries, chemistry, manufacturing and controls (CMC)

FDA goes over the IND within 30 days

after IND is human trials.

Phase 1

Phase 2

Phase 1: The goal is to determine safety and dosing (amount and frequency)

Phase 2: the goal is to test for effectiveness.  sample size hundreds.  run for years.

drug success discovery 1/10,000

SAR

Pharmacophore

SAR: structure-activity relationship.  finding the active molecule, and simplifying  it.

Pharmacophore: minimum structure required for activity

Target for drug action: modern drug discovery.  identify what the drug is interacting with

-receptors

-enzymes

-nucleic acids (RNA/DNA)

-excitable membranes and other biopolymers (anisthetics)

what the body does to the drug

tells how much drug, and how often to give

how much is present

how much is needed for effect

interactions

Absorption

Distribution

Metabolism

Excretion

receptors

enzymes

nucleic acids

excitable membranes

code of federal regulations controled by FDA

21

cGLP

cGMP

current good lab practices

current good manufacturing practices

phase 1

phase 2

phase 3

1: safety and dosing, amount and frequency

2: effectiveness

3: safety, effectiveness, dosage

abbreviated new drug application

(for generics)

orphan drug act

gov pays companys to research rare drugs

1983

exclusive marketing for 7 years

on/after 6/8/95: 20 years

applications pending 6/8/95: 16 years from issue date or 20 from fill date