Piyush Jain1, Ajay K Banga. 1. Department of Pharmaceutical Sciences College of Pharmacy & Health Sciences, Mercer University, Atlanta, Georgia 30341, USA.
Abstract
PURPOSE: To screen crystallization inhibitors, perform accelerated stability testing and predict saturation solubility of levonorgestrel in drug-in-adhesive patches. METHODS: Differential scanning calorimetry (DSC) studies were compared against slide crystallization studies for screening additives. Release studies were performed from crystallized and supersaturated patches. Die cutting was used for accelerated stability testing of patches. Time lag experiments were performed to predict saturation solubility of levonorgestrel in acrylate adhesive, DuroTak-2516. RESULTS: DSC studies indicated poloxamer to be the best additive whereas slide crystallization studies showed polyvinylpyrrolidone to be better. Supersaturated patches showed higher release profiles relative to crystallized patches. Crystals were observed in crystallized patches even after 96 h of release studies. Die-cutting of patches helped in development of crystals in less time as compared to uncut sheets indicating its usefulness in accelerated stability testing. Saturation solubility of levonorgestrel in DuroTak-2516 was predicted to be 0.09% w/w which was in close agreement with value of 0.1% w/w from solubility calculator on vendor's website. CONCLUSIONS: Crystallization was shown to have negative impact on drug release and patch performance. Slide crystallization studies, die cutting and time lag experiments can be used as tools to help stabilize the otherwise unstable patches.
PURPOSE: To screen crystallization inhibitors, perform accelerated stability testing and predict saturation solubility of levonorgestrel in drug-in-adhesive patches. METHODS: Differential scanning calorimetry (DSC) studies were compared against slide crystallization studies for screening additives. Release studies were performed from crystallized and supersaturated patches. Die cutting was used for accelerated stability testing of patches. Time lag experiments were performed to predict saturation solubility of levonorgestrel in acrylate adhesive, DuroTak-2516. RESULTS: DSC studies indicated poloxamer to be the best additive whereas slide crystallization studies showed polyvinylpyrrolidone to be better. Supersaturated patches showed higher release profiles relative to crystallized patches. Crystals were observed in crystallized patches even after 96 h of release studies. Die-cutting of patches helped in development of crystals in less time as compared to uncut sheets indicating its usefulness in accelerated stability testing. Saturation solubility of levonorgestrel in DuroTak-2516 was predicted to be 0.09% w/w which was in close agreement with value of 0.1% w/w from solubility calculator on vendor's website. CONCLUSIONS: Crystallization was shown to have negative impact on drug release and patch performance. Slide crystallization studies, die cutting and time lag experiments can be used as tools to help stabilize the otherwise unstable patches.
Authors: Glenn A Van Buskirk; Daniel Arsulowicz; Prabir Basu; Lawrence Block; Bing Cai; Gary W Cleary; Tapash Ghosh; Mario A González; David Kanios; Margareth Marques; Patrick K Noonan; Terrance Ocheltree; Peter Schwarz; Vinod Shah; Thomas S Spencer; Lino Tavares; Katherine Ulman; Rajendra Uppoor; Thean Yeoh Journal: AAPS PharmSciTech Date: 2012-01-04 Impact factor: 3.246
Authors: Sindhu S Ganti; Sonalika A Bhattaccharjee; Kevin S Murnane; Bruce E Blough; Ajay K Banga Journal: Int J Pharm Date: 2018-08-17 Impact factor: 5.875