Harold A. Nash and Dale N. Robertson are retired.
Release-modulating factors strongly affecting steroid diffusion from silicone elastomer†
Article first published online: 21 JUL 2004
Copyright © 2004 Wiley-Liss, Inc.
Journal of Pharmaceutical Sciences
Volume 93, Issue 10, pages 2420–2430, October 2004
How to Cite
Nash, H. A., Robertson, D. N. and Evans, S. J. (2004), Release-modulating factors strongly affecting steroid diffusion from silicone elastomer. J. Pharm. Sci., 93: 2420–2430. doi: 10.1002/jps.20158
- Issue published online: 21 JUL 2004
- Article first published online: 21 JUL 2004
- Manuscript Accepted: 25 MAY 2004
- Manuscript Revised: 18 MAY 2004
- Manuscript Received: 27 JAN 2004
- polymeric drug delivery systems;
Investigations were undertaken to determine the cause of decreases over time in the release rate from levonorgestrel (LNG) implants consisting of silicone elastomer tubing filled with crystalline steroid. Emptying and refilling with the same steroid partially restored release rate. Surprisingly, a further increment in release rates was attained if the tubing was briefly irrigated with methanol before refill. Fractional crystallization showed that release-modulating factors could be concentrated in mother liquors and were initially present as impurities. Boiling LNG in ethanol or methanol produced a number of release-modulating factors of which the most prominent was also found in one production lot of LNG. It was identified as 6β-hydroxy-levonorgestrel (6β-OH-LNG). Added to LNG at the 2% level, 6β-OH-LNG decreased the release rate by 27%. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2420–2430, 2004