Dosage form factors affecting bioavailability

Question 1

Surface active agents

Answer 1

effects on drug bioavailability are variable

depends on whether concentration of surfactant is above or below critical micelle concentration.

Three general mechanisms by which surface active agents influence drug bioavailability :

• Increase dissolution rates of poorly soluble drugs
• increase the permeability of the GI membrane
• solubilisation of drugs into surfactant micelle

Question 2

Drug-excipient complexation

Answer 2

if a drug forms a poorly soluble complex with an excipient present in the dosage form, a reduction in drug bioavailability usually occurs.

Soluble drug-excipient complexes usually dissociate readily in the GI fluids liberating the drug. In such cases complexation has little or no effect on drug bioavailability. complexation sometimes used to increase solubility of poorly soluble drugs

Question 3

Type of dosage form

Answer 3

the type of dosage form and its method of preparation or manufacture can influence bioavailability

types of oral dosage form influences the number of possible intervening steps between administration of the dosage form and the appearance of dissolved drug in the GI fluids.

The rate of drug appearance is likely to be faster from a capsule than a tablet

Question 4

Aqueous solution dosage forms

Answer 4

Formulation factors which may influence bioavailability of a drug from an aqueous solution include :

• chemical stability
• formation of a poorly absorbed, irreversible complex between drug and some excipient dosage form.
• solubilisation of the drug in surfactant micelles.
• viscosity of solution dosage form, particularly if viscosity- enhancing agent is included

Precipitation of a drug can occur when an aqueous solution dosage form is exposed to gastric fluid

However extremely fine nature of precipitated drub permits drug to re-dissolve rapidly when it reaches the duodenum

Question 5

Non aqueous solution dosage forms

Answer 5

For drugs which are poorly water soluble a non aqueous solution offers an alternative dosage form to an aqueous suspension, hard gelatine capsule or tablet

poorly soluble drugs dissolved in water miscible non aqueous solvents are likely to be precipitated in the gastric fluid when the soft gelatin capsule shell dissolves or disrupts

a poorly soluble drug in a hard gelatin capsule may never achieve the same degree of dispersion in the GI fluids that is achieved with a finely sub divided and well formulated aqueous suspension dosage form.

Question 6

formulation factors associated with aqeueous suspension dpsage which can influence drug bioavailability include

Answer 6

• particle size
• crystal form
• drug excipient complexation
• viscosity exhibited by the suspension in the GI fluids

Question 7

Hard gelatin capsule dosage forms

Answer 7

Provided that drug particles contained inside the capsule are dispersed rapidly and efficiently, a relatively large effective SA of a poorly soluble drug will be presented to the fluids.

A higly aqueous soluble diluent is usually more effective than an insoluble diluent in increasing the dissolution rate of an encapsulated drug.

Inclusion of a surfactant can also improve drug dissolution rate .

Question 8

Tablet dosage forms

Answer 8

When a drug is formulated into a compressed tablet, there is an enormous reduction in the effective SA of the drug.

Many bioavailability problems are associated with this reduction in effective SA.

These problems are most pronounced with poorly aqueous soluble drugs.

Disintegration of tablets into granules increases the effective SA of the drug . this leads to better dissolution

Question 9

Coated tablet

Answer 9

A coating presents a physical barrier between tablet core and the GI fluids

the physiochemical nature and thickness of the coating may influence the overall bioavailability