Dose Form Design EXAM 1

• 1) Random / Accidental
• 2) Targeted Screening
• 3) Molc. modification / mechanism-based

• 1) Botanical
• 2) Animal
• 3) Chemical
• 4) Genetic engineering

Plant extracts

• 1) hormones
• 2) serums
• 3) vaccines

May cause an immunoresponse

• 1) recombinant DNA (rDNA)
• 2) monoclonal antibody therapy (MoAb)
• 3) gene therapy

the ideal drug with full theraputic efficacy and no side effects

prototype compound with fundamental desired pharmacologic / biologic activity that may or may not be modified to improve desired function / features

an inactive substance requiring metabolic transformation to become pharmacologically active

Prodrugs can be designed for better solubility, absorption, biostability, and/or prolonged release

Combine a drug with it's prodrug...the active drug is released immediately and the prodrug is metabolized and released later for an extended effect

• -complex / time consuming process
• -work must be conducted over different fields
• -disease process must be researched
• -large $ investment

• Proprietary: patented trademark or brand name given to manufacurers
• Nonproprietary: generic name given by USAN council specifically for each compound

• Empirical: # of atoms and their relationships / ratios (ex: C₁₄H₁₉Cl₂NO₂)
• Systematic: descriptive name with relative locations of each atom (ex: 2-chloroethyl p-amino acid)

• -any new chemical entitiy
• -a new use for an established drug
• -a new dosage schedule / regimen
• -a new route of admin.
• -a new dosage form
• -change in drug's formulation / manufacturing
• -new combo of existing drugs

Manufacturer ("Labeler Code")

Drug Formulation ("Product Code")

Package size and type ("Package Code")

• 1) Biologic characterization of the drug
• 2) Formulation studies
• 3) INDA
• 4) NDA
• 5) Post-market surveillance

• -animal studies: 18mos+
• -review of data: 1mo+
• -phase I: 10mos+
• -phase II: 18mos+
• -phase III: 45mos+
• -review of data: 12mos+

To establish safe dosage range and toxic side effects. If too toxic, no human trials

Sponsor proposes protocol and requests permission of FDA to test on humans. FDA has at least 30 days to evaluate data of drug and data from animal studies before approving / denying.

• -sound statistical methods
• -qualified researches
• -suitable basis for choosing test subjects
• -safeguards to protect subjects

• -kinds of patients to be studied
• -conditions / parameters to be measured
• -how data will be collected / reported

• Clinical Investigator is the "middle-man" between the sponsor and the Institutional Review Board who conducts trials on human subjects.
• Must provide - statement of education, scientific training, experience, and signed statement of ethics

• -purpose and duration of the study
• -risks / discomforts
• -alternative options / procedures
• -benefits
• -MUST be in subject's native language and in simple terms

• -"Ethics Committee" responsible to review and monitor biomedical research
• -has purview over hospitals, universities, clinics, etc
• -composed of docs, scientists and is ethnically diverse
• -is non-governmental / non-regulatory

• -risk to subjects are minimized
• -risks are "reasonable" in relation to benefits
• -selection of subjects is equitable
• -informed consent is documented
• -all data is monitored

When they are well designed and well conducted by qualified investigators using applied ethical principles

• -randomized
• -controlled for age, gender, disease state, etc
• -must be double-blind ; placebo controlled

• -study how drug is absorbed, processed, and excreted in healthy patients (~100)
• -effects on organs / tissues (healthy --> diseased?)
• -initail discovery of side effects
• -how much drug should be taken and how often
• -safety precautions

13 to 14 out of 20 (~67%)

• -determines drug effectiveness in treating people with the disease (~several hundred)
• -get clearer picture of side effects and risks

5 to 6 out of 20 (~25%)

• determines drug effectiveness in up to several thousand patients with the disease at different levels
• try to have a more diverse population and longer term of study (3-6 years)
• find optimum dosage and less common side effects

• When a disease has no current known cure
• Drugs with strong evidence for a disease of high leathality (ex:AIDS)

composition, toxicology, drug behavior in body, testing results, manufacturing process, labeling

inspection of machinery and facilities, review of data, final approval by Advisory Committee

• ongoing perpetual monitoring of unexpected side effects in order to change drug labels or provide new warnings
• "phase IV" clinical trials

formulation, manufacturing, stability, effectiveness

The initial formulation that gets scaled-up for mass production (handmade-->machine)

reduction of particle size via mortar and pestle

the use of a mortar and pestle

• affects formulation and efficacy
• smaller particles are better absorbed due to incr. surface area

• crystalline vs amorphous forms
• crystals dissolve more slowly and amorphous forms dissolve more quickly

therapeutic effect - the body is an aqueous system

• esters are more pleasant smelling / tasting
• salts have better solubility

can determine the drugs solubility in water and where it is absorbed in the body (acidic stomach vs basic intestines)

• a solvent to help increase the solubility of a poorly water-soluble substance
• ethanol, glycerin and PEGs often used

a drug is complexed with something to protect it from being destroyed in water

• the lipid/water solubility
• how the drug dissolves into organic and inorganic solvents and suggests how the drug will work in the body

• hydrolysis - interaction with water
• oxidation - interaction with oxygen
• polymerization - interaction with other chemicals
• decarboxylation - removal of carboxyl group
• deamination - removal of amine group