Anshuman A Ambike1, K R Mahadik, Anant Paradkar. 1. Department of Pharmaceutics, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune, 411 038, Maharashtra, India.
Abstract
PURPOSE: To obtain free flowing, stable, amorphous solid dispersions (SDs) of simvastatin (SIM), a drug with relatively lower glass transition temperature (T(g)) by spray drying technique, and to perform comparative in vivo study in rats, which could justify the improvement in rate and extent of in vitro drug release. METHODS: Dichloromethane suspensions of SIM either alone or in combination with PVP (1:1 or 1:2 parts by weight) were spray dried with proposed quantity of Aerosil 200 (1:1, 1:1:1, 1:2:2 parts by weight of SIM, Aerosil 200 and PVP, respectively). SDs were characterized initially in comparison with pure drug and corresponding physical mixtures in same ratios by drug content, saturation solubility, SEM, DSC, XRPD, IR, and in vitro drug release. SD 1:2:2 was further subjected to accelerated stability testing and checked for in vitro drug release and presence of crystallinity using DSC and XRPD. In addition, improvement in rate and extent of in vitro drug release from SD 1:2:2 was justified by in vivo study in rats. RESULTS: Combination of SD and surface adsorption techniques has been attempted to overcome the limitations of spray drying technique for amorphization of low T(g) drugs. Based on powder characteristics, drug content, saturation solubility, and feasibility of processing into tablets; SD 1:2:2 was selected as the optimized formulation. During initial characterization, SEM, DSC, and XRPD analyses confirmed the presence of amorphous form in SD 1:2:2. IR spectroscopy revealed possibility of hydrogen bonding interaction between SIM and PVP in SDs. Also, there was dramatical improvement in rate and extent of in vitro drug release of SD 1:2:2. Insignificant decrease in dissolution was observed with no evidence of crystallinity during accelerated stability studies of SD 1:2:2. Moreover in vivo study in rats also justified the improvement in therapeutic efficacy of SD 1:2:2 over pure SIM. CONCLUSIONS: Thus, present study demonstrates high potential of spray drying technique for obtaining stable amorphous SDs of low T(g) drugs.
PURPOSE: To obtain free flowing, stable, amorphous solid dispersions (SDs) of simvastatin (SIM), a drug with relatively lower glass transition temperature (T(g)) by spray drying technique, and to perform comparative in vivo study in rats, which could justify the improvement in rate and extent of in vitro drug release. METHODS:Dichloromethane suspensions of SIM either alone or in combination with PVP (1:1 or 1:2 parts by weight) were spray dried with proposed quantity of Aerosil 200 (1:1, 1:1:1, 1:2:2 parts by weight of SIM, Aerosil 200 and PVP, respectively). SDs were characterized initially in comparison with pure drug and corresponding physical mixtures in same ratios by drug content, saturation solubility, SEM, DSC, XRPD, IR, and in vitro drug release. SD 1:2:2 was further subjected to accelerated stability testing and checked for in vitro drug release and presence of crystallinity using DSC and XRPD. In addition, improvement in rate and extent of in vitro drug release from SD 1:2:2 was justified by in vivo study in rats. RESULTS: Combination of SD and surface adsorption techniques has been attempted to overcome the limitations of spray drying technique for amorphization of low T(g) drugs. Based on powder characteristics, drug content, saturation solubility, and feasibility of processing into tablets; SD 1:2:2 was selected as the optimized formulation. During initial characterization, SEM, DSC, and XRPD analyses confirmed the presence of amorphous form in SD 1:2:2. IR spectroscopy revealed possibility of hydrogen bonding interaction between SIM and PVP in SDs. Also, there was dramatical improvement in rate and extent of in vitro drug release of SD 1:2:2. Insignificant decrease in dissolution was observed with no evidence of crystallinity during accelerated stability studies of SD 1:2:2. Moreover in vivo study in rats also justified the improvement in therapeutic efficacy of SD 1:2:2 over pure SIM. CONCLUSIONS: Thus, present study demonstrates high potential of spray drying technique for obtaining stable amorphous SDs of low T(g) drugs.
Authors: H Cheng; S C Sutton; J D Pipkin; G M Zentner; J D Rogers; J I Schwartz; Y B Mitchel; K Grasing; M S Schwartz; R D Amin Journal: Pharm Res Date: 1993-11 Impact factor: 4.200