Gastrointestinal Absorption: Role of the Dosage Form Bioavailability Solution>suspension>capsule>tablet>coated tablet

Solution: drugs that are water soluble and stable in aq solution Eliminates in vivo dissolution step Rate limiting step in abs. Weak acidic drug, administered as salt Solubility of poorly soluble drug

Suspensions: insoluble or poorly soluble drugs Absorption rate is dissolution rate limited, however Particles diffuse rapidly through the GIT Dissolution starts immediately Factors to be considered in the formulation of a suspension Particle size (surface area) Crystal form and polymorphism Complexation Wetting agents Viscosity

Hard gelatin capsules Bioavailability is better than a compressed tablet Overall rate of dissolution: Dissolution rate of the shell Rate of penetration of GI fluids into the encaps. Mass Rate of mass deaggregation Rate of dissolution of the dispersed mass Hydrophilic excipients Wetting agents Lubricants Formulation and type of filling process

Formulation factors that might influence the bioavailability of capsules Surface area and particle size of the drug Crystal form Nature and quantity of diluent, lubricant and wetting agent Drug-excipient interactions Filling process Packing density of the powder Type and composition of the shell (enteric shell) Interactions between shell and capsule components

Soft gelatin capsules Combine the convenience of unit dosage form with rapid abs of liquids and suspensions Drug is dissolved or dispersed in a non-toxic non-aq vehicle Drug release: water miscible vehicle water immiscible vehicle Formulation factors to be taken into consideration Solubility of the drug in the vehicle Particle size of the drug Nature of the vehicle Inclusion of surfactant, emulsifying agent Complexation

Tablets Most widely used dosage form Produced by wet granulation or direct compression Bioavailability problems: reduction of SA and generation of well disp. drug particles Formulation factors: Lubricants Compression force (tablet hardness)

Coated tablets Sugar coating, film coating Sugar coating: sealing: shellac, cellulose acetate phthalate Film coating: Water miscible: hydroxypropyl methycelullose, carboxymethylcellulose Water insoluble: ethylcellulose, acrylic resins

Press coated tablets Enteric coated tablets Special film coat that resists gastric fluids Polymers: cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate and polyvinyl acetate phthalate

DISSOLUTION AND DRUG RELEASE TESTING Dissolution and drug release tests are in-vitro tests that measure the rate and extent of dissolution or release of the drug substance from a drug product, usually in an aqueous medium under specified conditions. The dissolution test is an important quality control procedure for the drug product and is often linked to product performance in vivo. In-vitro drug dissolution studies are most often used for monitoring drug product stability and manufacturing process control.

As a quality control test, dissolution and drug release testing may be used for: Batch-to-batch drug release uniformity Stability Scale-up and postapproval changes (SUPAC) Predicting in-vivo performance

Dissolution Conditions The development of an appropriate dissolution test requires the investigator to try different agitation rates, different media (including volume and pH of medium), and different kinds of dissolution apparatus. Once a suitable dissolution test is obtained, acceptable dissolution criteria are developed for the drug product and its formulation. These criteria or dissolution specifications (eg, percent of drug dissolved in 30 minutes) are used to investigate formulation problems.

COMPENDIAL METHODS OF DISSOLUTION