Characterization of the gastrointestinal transit and disintegration behavior of floating and sinking acid-resistant capsules using a novel MRI labeling technique

Abstract

The application areas of hard capsules are currently widened by the introduction of acid-resistant capsule shells. In this study, the gastrointestinal behavior of acid-resistant hard capsule formulations as well as the influence of their density on the gastric residence time were characterized using magnetic resonance imaging (MRI). As labeling material for a reliable identification of the capsules in the MR images, small pieces of dried pineapple were used as they provide a high T1 signal. Tested products were DRcaps™ as capsule in capsule (Cap-in-Cap) system (outer capsule size 00). For the investigation of the influence of the capsule density on the gastric residence time, a floating low-density Cap-in-Cap capsule formulation and a sinking high-density Cap-in-Cap capsule formulation were investigated. The study was performed in eight healthy human subjects under fasting conditions. Besides the transit data of the capsule systems, the intraluminal fluid volume kinetics were determined using T2 weighted sequences. The gastric emptying times of the systems did not differ, with mean values of 45 ± 35 min for floating DRcaps™ and 36 ± 18 min for the sinking DRcaps™. The difference in density had no remarkable influence on gastric emptying. Thus, the concept of floating capabilities for gastroretentive dosage forms seems rather implausible. Furthermore, this assures transferability of common knowledge about dosage form transit for estimation of the performance of acid-resistant capsule shells, which most typically float. The mean disintegration times amounted to 139 ± 35 min for the floating DRcaps™ Cap-in-Cap and 163 ± 55 min for the sinking DRcaps™ Cap-in-Cap. In only one case, a sinking DRcaps™ Cap-in-Cap system disintegrated during gastric emptying, but all other capsules disintegrated in the small intestine, irrespective of their gastric residence time. The use of dried pineapple as labeling material could be successfully demonstrated as a reliable and easy method for the tracking of the transit and disintegration behavior of orally administered drug delivery systems, leading to a thorough understanding of their in vivo performance.

Keywords: Dosage form tracking; Gastro-resistant capsules; Gastrointestinal transit; Gastroretention; Magnetic resonance imaging; Site specific drug delivery.