title: Wetting Kinetics: an Alternative Approach Towards Understanding the Enhanced Dissolution Rate for Amorphous Solid Dispersion of a Poorly Soluble Drug.
abstract: Developing amorphous solid dispersions of water-insoluble molecules using polymeric materials is a well-defined approach to improve the dissolution rate and bioavailability. While the selected polymer plays a vital role in stabilizing the amorphous solid dispersion physically, it is equally important to improve the dissolution profile by inhibiting crystallization from the supersaturated solution generated by dissolution of the amorphous material. Furthermore, understanding the mechanism of dissolution rate enhancement is of vital importance. In this work, wetting kinetics was taken up as an alternative approach for understanding the enhanced dissolution rate for amorphous solid dispersion of a poorly soluble drug. While cilostazol (CIL) was selected as the model drug, povidone (PVP), copovidone, and hypromellose (HPMC) were the polymers of choice. The concentrations against time profiles were evaluated for the supersaturated solutions of CIL in the presence and absence of the selected polymers. The degree of supersaturation increased significantly with increase in polymer content within the solid dispersion. While povidone was found to maintain the highest level of supersaturation for the greatest length of time both in dissolution and solution crystallization experiments, copovidone and hypromellose were found to be the less effective as crystallization inhibitor. The ability of polymers to generate and maintain supersaturated drug solutions was assessed by dissolution studies. The wetting kinetics was compared against the solid dispersion composition to establish a correlation with enhanced dissolution rate.
authors: Centre for Pharmaceutical Sciences, Jawaharlal Nehru Technological University, Kukatpally, Hyderabad, 500 085, India. sanjayverma9@yahoo.com.|Aizant Drug Research Solutions Pvt Ltd, Sy. No. 172 and 173, Apparel Park Road, Dulapally, Hyderabad, 500 014, India. sanjayverma9@yahoo.com.
authors: Sanjay
authors: S
authors: Verma
authors: Aizant Drug Research Solutions Pvt Ltd, Sy. No. 172 and 173, Apparel Park Road, Dulapally, Hyderabad, 500 014, India.
authors: Varma S
authors: VS
authors: Rudraraju
mesh_terms: D000077407:Cilostazol; D003460:Crystallization; D004339:Drug Compounding; D065347:Hypromellose Derivatives / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D011108:Polymers / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D012995:Solubility; D013777:Tetrazoles / Q000737:chemistry*; D014753:Vinyl Compounds / Q000737:chemistry; D014867:Water / Q000737:chemistry*; D017155:Wettability
chemical_list: D011108:Polymers; D011759:Pyrrolidines; D013777:Tetrazoles; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D014867:Water; D065347:Hypromellose Derivatives; D011205:Povidone; D000077407:Cilostazol
keywords: Cilostazol; Crystallization inhibition; Solid dispersions; Supersaturated solutions; Wetting kinetics