ACCOUNTING FOR ABSORPTION AND HYDRODYNAMIC EFFECTS IN DISSOLUTION TESTING OF CONTROLLED RELEASE TABLETS

Abstract

Oral drug delivery is typically the most preferred route of administering drug into the body due to high patient compliance and ease of administration. However, compared to the intravenous route, bioavailability of the drug defined as the fraction of dose that reaches the bloodstream is much lower in oral delivery. This is because an orally delivered drug has to first pass through the complex environment of the gastrointestinal (GI) tract before getting absorbed into the blood in the intestine. Controlled release drug formulations are often used to enhance oral drug bioavailability, wherein a polymeric excipient is typically used to reduce drug precipitation/crystallization in the GI tract and to control drug release rate from oral dosage forms. The design of controlled release formulations involves the choice of appropriate polymer and the optimization of drug loading defined as the drug-polymer ratio, which necessitates the evaluation of many formulations of different composition. Although in vivo studies do provide the plasma drug concentration profile, they do not generally provide an insight into the fate of the formulation in the GI tract. In vitro experiments are therefore conducted to obtain a detailed understanding of the drug release behavior of controlled release formulations. Most commonly, these tests are performed using either a shaking flask (orbital shaker) or the United States Pharmacopeia (USP) 1 (basket) or USP 2 (paddle) apparatus, wherein the tablet is placed in a bowl containing buffer representative of the conditions in the GI tract. These may be used to analyze drug dissolution and the diffusion, swelling, and erosion processes of controlled release dosage forms. In vitro in vivo correlation (IVIVC) refers to the statistical correlation between in vivo and in vitro results, which are often used to deduce in vivo predictions from the results of in vitro experiments. In this work, I have mainly looked at two problems associated with the in vitro dissolution experiments and IVIVC of controlled release formulations.