In vitro dissolution absorption system (IDAS2): Use for the prediction of food viscosity effects on drug dissolution and absorption from oral solid dosage forms

摘要

Existing in vitro dissolution or permeation models to predict food effect are mainly based on Pharmacopeias' compendia) media, which specify such variables as pH, bile salts, lipolytic enzymes, and phospholipids content. However, the viscosity of food in the gastrointestinal (GI) tract is not taken into account, although it can affect both the dissolution of the oral solid dosage form and absorption of the released drug. Here, a new in vitro dissolution absorption system (IDAS2) is utilized, which comprises a dissolution apparatus USP2 (DISTEK) equipped with specially constructed permeability chambers containing Caco-2 monolayers, thereby allowing dissolution and transepithelial absorption to be ascertained simultaneously. The IDAS2 was used to evaluate the effect of medium viscosity on both the dissolution of oral solid dosage forms and absorption of released drugs. Such information, which is not ordinarily determined in dissolution and permeation studies, will be helpful to the formulators developing robust oral dosage forms. Commercially available solid dosage forms of ten model drugs from across all BCS classifications were used in this evaluation: metoprolol, minoxidil, and propranolol from BCS class 1; carbamazepine, ketoprofen, and simvastatin from BCS class 2; atenolol and ranitidine from BCS class 3; and acetazolamide and saquinavir from BCS class 4. The study revealed the applicability of IDAS2 as a tool for in vitro screening of dissolution and absorption of intact oral solid products to predict food viscosity effect. The most profound viscosity effect on dissolution and absorption was observed of solid dosage forms for the BCS class 2 compounds carbamazepine and simvastatin. A higher medium viscosity significantly slowed down the dissolution rate of tested BSC class 4 compounds acetazolamide and saquinavir, without significant effect on their absorption. The solid dosage forms least affected by the viscosity of the medium tested were the BCS class 1 compounds minoxidil and propranolol.