A Nomogram to Evaluate Intrinsic Absorption Rate Constants of Potential Oral Prolonged-Release Candidates

Abstract

The purpose of this study was to devise a simple method to determine whether or not a drug's absorption rate constant favored the selection of that drug for an oral prolonged-release drug delivery system (DDS). Computer simulations were used to observe the drug time-course in the DDS, the gastrointestinal tract, and the cumulative amount absorbed following administration of an 8-, 12-, and 24-hr zero-order DDS. For each DDS, the drug's intrinsic absorption rate constant, ka, was systematically varied from 0.1 to 10 hr-1. Results demonstrated that the DDS controlled the absorption rate whenever drug release was rate-limiting. However, the release rate did not determine the length of time that a DDS controlled the absorption rate. Instead, the duration of DDS-controlled absorption increased as the ka value increased. When ka > or = 2 hr-1, the DDS controlled more than 80% of the 8-, 12-, and 24-hr dosing intervals. Conversely, when ka < or = 0.12 hr-1, the DDS failed to control absorption. In conclusion, this investigation developed a technique to ascertain the rate-limiting step when a zero-order DDS releases a drug that undergoes first-order absorption. This technique was employed to construct a nomogram that allows its users to estimate the duration of control by an 8-, 12-, or 24-hr DDS based on the ka value for the drug.