Biphasic Drug Release from Rolled-Up Gelatin Capsules with a Cylindrical Cavity.

Abstract

Biphasic drug delivery systems are used for quick release of a specific amount of drug for immediate amelioration of a patient’s state, followed by sustained release, to avoid repeated administration. This type of delivery is often necessary for pain management and the treatment of many pathologies, such as migraines, hypertension, and insomnia. In this work, we propose a novel architecture of a biphasic release media that does not need the rapidly disintegrating layer and that allows for easily setting the sustained release rate. A drug-containing capsule is made by rolling up a thermally crosslinked gelatin strip on which drug reservoirs are formed by casting. The quick-release reservoir (QRR) is placed at the strip’s extremity, from which the rolling starts, while the sustained-release reservoir (SRR) is formed in the middle part of the strip. The strip is rolled around a cylinder that is a few millimeters wide, which is removed after rolling. The roll is stabilized by transglutaminase-catalyzed crosslinking of the consecutive shells. A biphasic release is successfully demonstrated with the use of model fluorescent drugs for single-dye and double-dye systems in phosphate-buffered saline (PBS) solution with pH = 7.4. In vitro, the drug from the QRR, placed at the walls of the cavity of the roll, is released immediately upon the capsule’s contact with the PBS solution. The drug from the SRR, embedded between the roll’s layers, diffuses steadily, with the lag time defined by the radial position of the reservoir.