Photostability of Crystalline Versus Amorphous Nifedipine and Nimodipine

• Published in: Journal of pharmaceutical sciences Vol. 102; no. 6; pp. 1883 - 1894
• Main Authors: Grooff, Driekus, Francis, Farzaana, De Villiers, Melgardt M., Ferg, Ernst
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.06.2013; Wiley Subscription Services, Inc., A Wiley Company; Elsevier Limited
• Subjects: amorphous; chemical stability; Crystallization; Drug Stability; Kinetics; nifedipine; Nifedipine - chemistry; nimodipine; Nimodipine - chemistry; pharmaceuticals; photodegradation; Photolysis; polymorphism; solid-state stability; Vasodilator Agents - chemistry; X-Ray Diffraction; X-ray powder diffractometry; nifedipine; chemical stability; amorphous; photodegradation; solid-state stability; nimodipine; X-ray powder diffractometry; polymorphism; kinetics; pharmaceuticals
• DOI: 10.1002/jps.23533
• ISSN: 0022-3549

True solid-state photostability of the drugs nifedipine and nimodipine was investigated during exposure to UV-visible radiation. Photostability was studied on a small scale as thin films of approximately 1mg drug, which contained either amorphous or re-crystallised stable phases. High-performance liquid chromatography analysis revealed a greater rate and extent of decomposition for the amorphous phases. Photoexposed amorphous nifedipine exhibited approximately 1.8-fold larger first-order decomposition rate constant (k) relative to its crystalline phase. The increase in k was more significant for photoexposed amorphous nimodipine at approximately sixfold relative to its crystalline phase. Photodecomposition in scaled-up samples of the stable crystalline phases for both drugs was monitored with X-ray diffraction in Bragg-Brentano geometry. The similarities in the calculated photodecomposition extents to results from small scale validated the specificity of the X-ray analysis technique to the photodecomposition region. The considerably faster decomposition rates in small-scale studies were attributed to a maximised surface area (A) for quantity (m0) of exposed drug. Kinetic interpretations of true solid-state stability should consider the sample solid dimensions in terms of the direct exposed A and m0 in the photodecomposition region, that is, outer layers in solid.