Exploring the possible relationship between the drug release of Compritol®-containing tablets and its polymorph forms using micro X-ray diffraction

• Published in: Journal of controlled release 2015-01, Vol.197, p.158-164
• Main Authors: Jannin, Vincent, Rosiaux, Yvonne, Doucet, Jean
• Format: Article
• Language: English
• Subjects: Drug Stability; Excipients - chemistry; Fatty Acids - chemistry; Tablets; Theophylline - chemistry; X-Ray Diffraction
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2014.11.013

Lipid excipients are more and more commonly used in the pharmaceutical industry as sustained drug delivery agents. However, their development may still be hindered by the well-known polymorphism of lipids which is perceived as a disadvantage with possible impact on drug release upon storage. In order to explore the eventual link between drug release modification and lipid polymorphism, we used a synchrotron radiation-based micro X-ray diffraction that allows probing the crystalline structures of the lipid matrix-forming excipient at a local scale and scanning it across the whole tablet. This technique demonstrated that only one polymorph of Compritol® 888 ATO is present in each tablet. This polymorph is identical whatever the compression force applied during the manufacturing is, and stays the same after storage at 40°C for 45days, even if these tablets exhibit different drug release profiles. Hence modification of drug release observed after storage is not due to lipid polymorphism. Implementation of post-compression thermal treatments generates another lipid polymorph. Again drug release is not linked with polymorphism because two different polymorphs of Compritol® 888 ATO lead to exactly the same dissolution profile. Variation of drug release observed during storage in accelerated conditions could be attributed to an altered distribution of the lipid component within the matrix structure. The lipid may flow within the matrix structure and increase the hydrophobicity of tablets.