Fang Zhao1, Vyacheslav Malayev, Venkatramana Rao, Munir Hussain. 1. Biopharmaceutics R&D, Pharmaceutical Research Institute, Bristol-Myers Squibb Company, One Squibb Drive, P. O. Box 191, New Brunswick, NJ 08903, USA. fang.zhao@bms.com
Abstract
PURPOSE: Sodium lauryl sulfate (SLS) is a commonly used surfactant in dissolution media for poorly water soluble drugs. However, it has occasionally been observed that SLS negatively impacts the dissolution of drug products formulated in gelatin capsules. This study investigated the effect of SLS on the dissolution of hard gelatin capsule shells. METHODS: The USP paddle method was used with online UV monitoring at 214 nm (peptide bond). Empty size #0 capsule shells were held to the bottom of the dissolution vessel by magnetic three-prong sinkers. RESULTS: SLS significantly slowed down the dissolution of gelatin shells at pH < 5. Visually, the gelatin shells transformed into some less-soluble precipitate under these conditions. This precipitate was found to contain a higher sulfur content than the gelatin control sample by elemental analysis, indicating that SLS is part of the precipitate. Additionally, the slowdown of capsule shell dissolution was shown to be dependent on the SLS concentration and the ionic strength of the media. CONCLUSIONS: SLS interacts with gelatin to form a less-soluble precipitate at pH < 5. The use of SLS in dissolution media at acidic pH should be carefully evaluated for gelatin capsule products.
PURPOSE:Sodium lauryl sulfate (SLS) is a commonly used surfactant in dissolution media for poorly water soluble drugs. However, it has occasionally been observed that SLS negatively impacts the dissolution of drug products formulated in gelatin capsules. This study investigated the effect of SLS on the dissolution of hard gelatin capsule shells. METHODS: The USP paddle method was used with online UV monitoring at 214 nm (peptide bond). Empty size #0 capsule shells were held to the bottom of the dissolution vessel by magnetic three-prong sinkers. RESULTS:SLS significantly slowed down the dissolution of gelatin shells at pH < 5. Visually, the gelatin shells transformed into some less-soluble precipitate under these conditions. This precipitate was found to contain a higher sulfur content than the gelatin control sample by elemental analysis, indicating that SLS is part of the precipitate. Additionally, the slowdown of capsule shell dissolution was shown to be dependent on the SLS concentration and the ionic strength of the media. CONCLUSIONS:SLS interacts with gelatin to form a less-soluble precipitate at pH < 5. The use of SLS in dissolution media at acidic pH should be carefully evaluated for gelatin capsule products.
Authors: Festo Damian; Mohammad Harati; Jeff Schwartzenhauer; Owen Van Cauwenberghe; Shawn D Wettig Journal: Pharmaceutics Date: 2021-02-04 Impact factor: 6.321