Controlling drug delivery from polymer microspheres by exploiting the complex interrelationship of excipient and drug crystallization

摘要

Semicrystalline polymers are often used as macromolecular excipients in active pharmaceutical ingredient (API)-delivery systems. In such systems, the morphological structure and crystalline characteristics of the excipient have a direct impact upon the drug-delivery rate. In this study, polycaprolactone (PCL)-based microspheres prepared via melt-printing were loaded with 10, 30, and 50% ibuprofen (IBU). In vitro release studies showed that, for a constant amount of IBU, the API was released fastest from the 30%-loaded microspheres, followed by the 50%- and 10%-loaded microspheres. The discrepancy in these release rates was investigated using scanning electron microscopy, differential scanning calorimetry, X-ray diffraction, and thermodynamic analyses, revealing the complex morphological and crystalline interrelationships of PCL and IBU. Although it is generally accepted that the degree of crystallinity of the excipient is the main factor controlling the release of the API, we found that the crystallite size of the small-molecule API is of primary importance. Moreover, these factors, which are controllable via the parameters used in melt-based preparation, can be exploited to tune drug-release rates. (c) 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47227.