Biopharmaceutics/Drug Dissolution Bioavailability & Bioequivalence

Dissolution

the process by which drug (particles) dissolve

For drug absorption, it must be first dissolved in the fluid at the

absorption site

What factors affect drug dissolution?

physicochemical factors, physiological factors

What are examples of physicochemical factors?

drug, dosage form

Noyes Whitney equation

describes dissolution

• dc/dt = rate of dissolution
• k = dissolution rate constant
• S = Surface area of the dissolving solid
• Cs = saturation concentration of drug in the diffusion layer
• Ct = concentration of the drug in the dissolution medium at time

Sometimes, ______ of drugs may be used because of greater stability than
the corresponding amorphous forms

crystalline form

When a drug particle is reduced to a larger number of smaller particles, the total surface area

created is ___________.

increased

For drug substances that are poorly or slowly soluble, decreasing particle size generally

results in an ___________ in the rate of dissolution.

increase

Which form of a compound has more solubility?

amorphous form of a compound has more solubility than its crystalline form

Sodium and potassium salts of weak organic acids and hydrochloride salts of weak
organic bases dissolve ___________ than do their respective free acids or bases.

more readily

What form is more readily soluble than the hydrated form?

anhydrous

Anhydrous ampicillin has _________ solubility than ampicillin trihydrate

higher aqueous

Formation of less soluble complexes resulting in reduced

absorption

Tetracycline analogues form complexes with calcium, magnesium and

aluminum.

▪ _____________ absorption of the tetracycline complexes

decreased

Adsorption – to the insoluble material in the GIT
▪ ___________ availability for absorption

decreased

types of dosage forms

tablet, capsule, solution

Bioavailability

The rate and extent to which an active drug ingredient or therapeutic moiety is absorbed from a drug product and becomes available at the site of drug action.

Bioequivalence

The comparison of bioavailabilities of different formulations, drug products, or batches of the same drug product

Proprietary drug products are also known as ___

brand drugs

Non-proprietary drug products are also known as ____

generic drugs

Standardized nomenclature of drugs are established by:

▪ USAN (United States Adopted Names) Council

▪ WHO (World Health Organization)

Generic drug product

A pharmaceutical product that can substitute a brand product.

▪ Must show similar drug profile in plasma as its brand product (bioequivalent).

What should be the same for brand and generic products?

▪ The active ingredient (drug) & strength

▪ The dosage form

The following equivalencies play an important role in establishing a generic drug

▪ Pharmaceutical equivalent

▪ Pharmaceutical alternative

▪ Bioequivalent

▪ Therapeutic equivalent

Pharmaceutical equivalents are drug products that:

▪ Contain identical active ingredient, i.e., the same salt or ester of the parent drug

▪ Are identical in strength or concentration (of the drug)

▪ Contain identical dosage forms

▪ Have identical route of administration

▪ Meet the identical compendial or other applicable standard of identity, strength, quality, and purity,

including potency and, where applicable, content uniformity, disintegration times, and/or dissolution

rates

Pharmaceutical equivalents may differ in:

Shape, drug release mechanism, labeling, excipients (including colors, flavors, etc.)

Pharmaceutical alternatives

drug products that contain the identical therapeutic moiety, or its precursor, but not necessarily in the same amount or dosage form or as the same salt or ester.

Bioequivalent drug products

pharmaceutical equivalents or pharmaceutical alternatives whose rate and extent of absorption do not show a significant difference when administered at the same molar dose of the therapeutic moiety under similar experimental conditions, either single dose or multiple dose.

Therapeutic equivalents

Used to indicate pharmaceutical equivalents which, when administered to

the same individuals in the same dosage regimens, will provide essentially

the same therapeutic effect.

The FDA classifies therapeutically equivalent products as those that meet the following

general criteria:

▪ They are approved as safe and effective

▪ They are pharmaceutically equivalent

▪ They are bioequivalent

▪ They are manufactured incompliance with Current Good Manufacturing Practice

(cGMP) regulations

▪ They are adequately labeled

how does gastric emptying rate affect drug absorption with a fasting stomach?

speeds up the rate of drug absorption because most oral drugs are absorbed in the small intestine rather than the stomach.

how does GI tract transit time affect drug absorption?

stomach: 2-4 hrs

small intestine: 4-10 hrs

How does Co-administration of other drugs affect drug absoprtion?

Other drugs can increase or decrease drug absorption

How does age of the patient affect drug absorption?

Most physiological functions are decreased, absorption mostly stays the same

How does food taken by the patient affect drug absoprtion?

Most drugs are absorbed more slowly with food

How does disease state of the patient affect drug absoprtion?

Disease can alter drug absorption by changing GI function

Explain the effect of particle size on surface area

Explain the effect of particle size on surface area

Explain the effect of particle size on surface area

lower particle size = higher surface area

Explain the effect of particle size on solubility

lower particle size = higher solubility

Explain the effect of particle size on dissolution rate

lower particle size = higher dissolution rate

Explain the effect of particle size on absorption rate of a poorly water soluble drug

lower particle size = increased absorption