(386f) Tablet Design and the Potential Impact on Oral Drug Delivery

Authors: 
Achenie, L. E. K., Virginia Polytechnic Institute and State University
Pavurala, N., Virginia Tech


The oral administration route is by far the most common way of administering pharmacological substances. In oral drug delivery the challenge is for the drug active to be released in a controlled way from the solid tablet into the blood circulatory system in order to maintain the therapeutic blood plasma concentration levels following a time schedule. Good computational models are needed to predict the drug release and transport into the blood plasma. This would help in reducing the expense, time and effort involved in drug design. Several models are available in the literature describing either the release of drug from the tablet into the gastrointestinal (GI) tract or the transport of drug through GI tract into the blood plasma. We have contributed to the development of a composite computational model for an oral drug delivery system (involving a drug active within a solid polymer matrix), which describes the release as well as the transport of drug from the tablet through GI tract into the blood plasma.

We employ a modified form of the drug release model proposed by Balaji and Peppas [1] based on the following assumptions. As the polymer matrix comes into contact with bodily fluid (modeled as water) inside the digestive system, it penetrates the polymer matrix; the latter then swells forming a gel layer. Drug molecules are released through the gel layer into the digestive system, crossing the enterocyte membrane into the blood stream. In our strategy, we envision two stages in the transport of drug into the blood. Therefore we couple the drug release model with a compartmental absorption and transit model (CAT), see for example Yu and Amidon [2]. The drug release model (Stage 1) is a moving boundary problem consisting of partial differential equations (PDEs) and ordinary differential equations (ODEs) which describe the diffusion of (i) bodily fluid into the drug tablet; (ii) drug out of the tablet; and (iii) polymer chains through a boundary layer. The model accounts for two moving interfaces (namely, tablet/gel interface and gel/bodily fluids interface in the digestive system).

In this presentation we will discuss a strategy for tablet customization, namely designing the dosage form of the tablet based on a desired release profile inspired by a desired plasma concentration profile (therapeutic effect). Our efforts include the systematic identification of tablet geometry and designs that could give specific desired drug release profiles such as a constant release profile or a pulsatile release profile. We next couple the tablet customization with the GI transport model discussed above. We expect the proposed approach to aid in the drug development process and contribute to the development of personalized medicine.

1. Narasimhan, B. and N.A. Peppas, Molecular analysis of drug delivery systems controlled by dissolution of the polymer carrier. Journal of Pharmaceutical Sciences, 1997. 86(3): p. 297-304.

2. Yu, L.X. and G.L. Amidon, A compartmental absorption and transit model for estimating oral drug absorption. International Journal of Pharmaceutics, 1999. 186(2): p. 119-125.

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