Effect of Sodium Lauryl Sulfate in Dissolution Media on Dissolution of Hard Gelatin Capsule Shells
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.
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- 1.V. Shah, J. Konecny, R. Everett, B. McCullough, A. Noorizadeh, and J. Skelly. In vitro dissolution profile of water-insoluble drug dosage forms in the presence of surfactants. Pharm. Res. 6:612-618 (1989).Google Scholar
- 2.C. Noory, N. Tran, L. Ouderkirk, and V. Shah. Steps for development of a dissolution test for sparingly water-soluble drug products. American Pharmaceutical Review 4:16-18 (2002).Google Scholar
- 3.Y. Wu, S. Betigeri, G. Derbin, M. Franchini, M. Paborji, and F. Zhao. Dissolution studies of capsule formulations: the effects of fill weight, sinker type, surfactant, and capsule shell type. AAPS PharmSci. 3(3) (2001). http://www.aapspharmsci.org/.Google Scholar
- 4.Y. Wu, F. Zhao, and M. Paborji. Effect of fill weight, capsule shells, and sinker design on the dissolution behavior of capsule formulations of a weak acid drug candidate BMS-309403. Pharm. Dev. Tech. 8:379-383 (2003).Google Scholar
- 5.R. Soltero, J. Hoover, T. Jones, and M. Standish. Effects of sinker shapes on dissolution profiles. J. Pharm. Sci. 78:35-39 (1989).Google Scholar
- 6.J. Crison, N. Weiner, and G. Amidon. Dissolution media for in vitro testing of water-insoluble drugs: effect of surfactant purity and electrolyte on in vitro dissolution of carbamazepine in aqueous solutions of sodium lauryl sulfate. J. Pharm. Sci. 86:384-388 (1997).Google Scholar
- 7.R. Jones. Gelatin: physical and chemical properties. In K Ridgway (ed.), Hard Capsules—Development and Technology. The Pharmaceutical Press, London, 1987, pp. 31-48.Google Scholar
- 8.C. Nelson. The binding of detergents to proteins. I. The maximum amount of dodecyl sulfate bound to proteins and the resistance to binding of several proteins. J. Biol. Chem. 246:3895-3901 (1971).Google Scholar
- 9.E. Goddard, T. Phillips, and R. Hannan. Water soluble polymer-surfactant interaction—Part 1. J. Soc. Cosmet. Chem. 26:461-475 (1975).Google Scholar
- 10.D. Jon and D. Chang. Interactions between an amine function polymer and an anionic surfactant. J. Soc. Cosmet. Chem. 41:213-225 (1990).Google Scholar