title: Solid-state interaction of stearic acid with povidone and its effect on dissolution stability of capsules.
abstract: Capsule formulations of two drugs under development showed slower dissolution upon storage; Drug A, after 2.5 weeks at 40 degrees C/23% RH and 4 weeks at 30 degrees C/60% RH, and Drug B, after 6 weeks at 50 degrees C and 40 degrees C/75% RH. The formulations of both drugs contained povidone as a binder and stearic acid as a lubricant. Replacement of stearic acid by magnesium stearate from the formulation of Drug B, which was selected for further studies, provided rapid dissolution profiles under similar storage conditions with no change occurring on storage. In order to investigate the role of stearic acid further, binary mixtures of stearic acid with the drugs and other excipients used in their respective formulations were prepared and stored at 40 degrees C/75% RH and 50 degrees C. After 1 week of storage, it was observed that povidone and stearic acid mixture formed a transparent, hard, glass-like insoluble substance. It is hypothesized that the substance formed by the interaction can reduce the porosity of the granules and thereby reduces the ingress of the dissolution medium leading to slower dissolution. The infrared (IR) spectra of the glass-like substance showed a slight broadening of the povidone carbonyl band at 1662 cm(-1). The powder X-ray diffraction of the stored mixture showed that the crystallinity of stearic acid was lost. Furthermore, repeated heating and cooling cycles of povidone and stearic acid mixtures in various proportions using differential scanning calorimetry (DSC) showed that recrystallization of stearic acid from its melt was strongly affected by the presence of increasing amounts of povidone. Based on the observed solid-state interaction, a combination of stearic and povidone should be avoided for immediate release formulations.
authors.affiliation: Bristol-Myers Squibb Co., PO Box 191, New Brunswick, NJ 08903-0191, United States. divyakant.desai@bms.com
authors.forename: D
authors.initials: D
authors.lastname: Desai
authors.forename: S
authors.initials: S
authors.lastname: Kothari
authors.forename: M
authors.initials: M
authors.lastname: Huang
mesh_terms: D002152:Calorimetry, Differential Scanning; D002214:Capsules; D003460:Crystallization; D004344:Drug Incompatibility; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D006813:Humidity; D016062:Porosity; D011205:Povidone / Q000737:chemistry*; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry*; D013696:Temperature; D013997:Time Factors; D014961:X-Ray Diffraction
chemical_list: D002214:Capsules; D005079:Excipients; D013229:Stearic Acids; C031183:stearic acid; D011205:Povidone