Release-modulating factors strongly affecting steroid diffusion from silicone elastomer.
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 6beta-hydroxy-levonorgestrel (6beta-OH-LNG). Added to LNG at the 2% level, 6beta-OH-LNG decreased the release rate by 27%.
Nash
Harold A
HA
Center for Biomedical Research, Population Council, 1230 York Avenue, New York, NY 10021, USA. hnash@popcbr.rockefeller.edu
Robertson
Dale N
DN
Evans
Simone J
SJ
D002214:Capsules; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D002855:Chromatography, Thin Layer; D003460:Crystallization; D004339:Drug Compounding; D004343:Drug Implants; D016912:Levonorgestrel / Q000008:administration & dosage / Q000737:chemistry*; D000432:Methanol / Q000737:chemistry; D012826:Silicone Elastomers / Q000737:chemistry*
D002214:Capsules; D004343:Drug Implants; D012826:Silicone Elastomers; D016912:Levonorgestrel; D000432:Methanol