Estimating Intragastric Disintegration Times of Immediate Release Dose Units Administered After a High-Calorie, High-Fat Meal Using Standardized, Commercially Available Equipment and Materials.

Abstract

Intragastric disintegration times of immediate release (IR) dose units after high-calorie, high-fat meal would be useful in the assessment of drug absorption process and when considering waivers of bioequivalence assessment of non-high risk IR products in the fed state. We investigated the usefulness of standardized, commercially available equipment and materials in estimating intragastric disintegration times of IR dose units after high-calorie, high-fat meal. Disintegration times were estimated from the cumulative % drug in the medium vs. time data sets. When using 330 mL Level III FeSSGF-V3 and the compendial Apparatus II (60 rpm) with apex vessel without sinkers, the complete disintegration times of Panadol Actifast® tablets were close to previously estimated mean intragastric complete disintegration time (14 min), and the initial disintegration times of hard gelatine capsules were close to previously estimated mean intragastric initial disintegration time (11 min). Also, initial intragastric disintegration times of hard hypromellose capsules without gelling agents were predicted to be in line with intragastric initial disintegration times in the fasted state whereas disintegration of hard hypromellose capsules prepared with gelling agents was dramatically extended, in line with intragastric data after high-calorie, high-fat meal. Level III FeSSGF-V3 and the compendial Apparatus II (60 rpm) with apex vessel could be useful in estimating average intragastric disintegration times, in supporting justification for waiving in vivo bioequivalence studies, or in detecting non-IR characteristics of dose units after a high-calorie, high-fat meal.