Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Texas A&M University, College Station, Texas 77843.
Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Texas A&M University, College Station, Texas 77843.
J Pharm Sci. 2019 Jun;108(6):2112-2118. doi: 10.1016/j.xphs.2019.01.020. Epub 2019 Jan 24.
The commercial product of rifaximin (RFX) contains α form. The α form can change to β form on exposure to high humidity that can occur during manufacturing, stability, and in-use period. It is critical to maintain α form of the drug in a drug product to avoid variability in clinical response. U.S. Food and Drug Administration dissolution method was found to be nondiscriminatory for RFX formulations containing either 100% α or β form. The objective of this study was to develop a discriminatory dissolution method that can detect low levels of α to β transformation in RFX products. Formulations containing a variable fraction of α and β forms were prepared by using direct compression method. Dissolution parameters investigated were type of dissolution medium (water and phosphate buffer), volume (500, 900, and 1000 mL), and paddle speed (50, 75, and 150 rpm). Dissolution in water with 0.2% sodium lauryl sulfate was less than 80% and nondiscriminatory. However, dissolution tested in a phosphate buffer pH 7.4 with 0.2% sodium lauryl sulfate at 50 rpm was discriminatory with more than 17.5% difference in dissolution profile between formulations containing α and β forms. The developed method can detect polymorphic transformation if there is 25% or more β form conversion.
利福昔明（RFX）的商业产品含有α形式。在制造、稳定性和使用期间，α形式可能会因暴露于高湿度而转变为β形式。在药物产品中保持药物的α形式至关重要，以避免临床反应的可变性。美国食品和药物管理局的溶出度方法被发现对含有 100%α或β形式的 RFX 制剂没有歧视性。本研究的目的是开发一种具有区分能力的溶出度方法，以检测 RFX 产品中低水平的α到β转化。通过直接压缩法制备含有不同比例α和β形式的制剂。考察的溶出度参数有：溶出介质类型（水和磷酸盐缓冲液）、体积（500、900 和 1000 mL）和桨叶速度（50、75 和 150 rpm）。在含有 0.2%十二烷基硫酸钠的水中的溶出度小于 80%，且无歧视性。然而，在含有 0.2%十二烷基硫酸钠的磷酸盐缓冲液 pH 7.4 中，以 50 rpm 测试的溶出度具有区分能力，α 和β形式制剂的溶出曲线之间的差异超过 17.5%。如果有 25%或更多的β形式转化，所开发的方法可以检测到多晶型转化。
