Oral solids biopharmaceutics

Various dissolution test systems have been developed and several of them now enjoy compendial status in pharmacopeias, for example the reciprocating cylinder (United States Pharmacopeia Apparatus 3), the flow-through apparatus [European Pharmacopoeia (Pharm. Eur.) 2.9.3], or the apparatus for transdermal delivery systems, such as the paddle over disc. Hydrodynamic properties of these and other apparatus have been described only sparingly. The paucity of quantitative data related to hydrodynamics of pharmacopeial dissolution testers is lamentable, since well-controllable hydrodynamics are essential to both biopharmaceutical simulations and quality control. Here, we focus the discussion on the paddle and the basket apparatus, since these are the most important and widely used for oral solid dosage forms. A brief treatise on the hydrodynamics of the flow-through apparatus completes this section. 

Pharmaceutical excipients available on the market seem sufficient to support typical oral solid dosage form development. In some cases, new chug candidates have physicochemical and biopharmaceutical properties that are less than ideal. These chugs present formulation challenges and may require either the discovery of new excipients or improvement of existing excipients. From a regulatory perspective, there is no answer for the question of registration of an excipient as a separate entity. 

Waiver of in vivo bioavailability and bioequivalence studies for immediate release solid oral dosage forms based on a biopharmaceutics classification system. Center for Drug Evaluation and Research, Food and Drug Administration, issued 8/2000, posted 8/31/2000. http //www.fda.gov/cder/guidance/ index, htm... 

FDA Guidance for Industry Waiver of in vivo Bioavailability and Bioequivalence Studies for Immediate Release Solid Oral Dosage Forms Containing Certain Active Moieties/ Active Ingredients Based on a Biopharmaceutics Classification System, CDER-GUID 2062dft.wpd Draft, Jan. 1999. 

CDER Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system Food and Drug Administration, 2000. 

Centre for Drug Evaluation FDA (2000). Waiver of In Vivo Bio availability and Bioequivalence Studies for Immediate Release Solid Oral Dosage Forms Based on a Biopharmaceutical Classification System. Guidance for industry. 2000. 

Waiver of in vivo bioequivalence studies for major post approval manufacturing changes for the BCS Class I (Biopharmaceutics Classification System highly soluble, highly permeable and rapidly dissolving) solid oral products is NOT recommended for narrow therapeutic index drugs (17). 

Until recently, nonparenteral routes have failed to deliver sufficient quantities of ASO to be systemically therapeutic. The recent advent of novel oral delivery technologies, coupled with the increased tissue residence time for second-generation ASOs, allows oral delivery to achieve therapeutic levels for select systemic indications. This chapter will initially outline certain more conventional aspects of parenteral dosage forms, and then focus on formulation technologies that more specifically address local treatment. For the oral route, we will pass to the biopharmaceutic considerations for both local delivery to the gut and systemic delivery via absorption from solid dosage forms. Incumbent with the discussion on formulations is the need initially to overview the physico-chemical properties of ASOs, which in large part determine their biopharmaceutic characteristics. 

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