INVESTIGATING THE EFFECT OF MOLECULAR WEIGHT OF POLYVINYLPYRROLIDONE AND HYDROXYPROPYL METHYL CELLULOSE AS POTENTIAL ANTIPRECIPITANTS ON SUPERSATURATED DRUG SOLUTIONS AND FORMULATIONS USING WEAKLY ACIDIC DRUG: INDOMETHACINAbstract
Most of the drug discovered in past decade belongs to biopharmaceutical classification system (BCS) class II. The solubility of these drugs is the limiting factor for oral bioavailability. The drug can be present in solution in a supersaturated state; however, it has a tendency to crystallize out. In this paper, we aim to study the effect of molecular weight of Polyvinylpyrrolidone (PVP) (PVP K12, PVP K29 and PVP K90) and Hydroxypropyl methyl cellulose (HPMC) (HPMC E5, HPMC E15 and HPMC E50) as potential antiprecipitant on weakly acidic drug-Indomethacin (INDO). Supersaturation assay was carried out by solvent shift and solvent casting method. These are non-formulated methods and to access their ability to generate supersaturation, spray dried solid dispersions (SD) were prepared. Supersaturation assay revealed that the ability to generate and maintain the supersaturation are concentration dependent for PVP. As the molecular weight increases the supersaturation produced is increased in PVP and decreased for HPMC polymers. On stability, PVP solvent casts are affected the most. SD were prepared and found out that processability is much better for PVP K29 and HPMC E5. PVP K90 SD and HPMC SD when stored at elevated temperature and humidity show better stability. FTIR analysis showed the presence of hydrogen bonds between the polymer and INDO. Dissolution data revealed that at higher drug-loading PVP K90 and HPMC E50 show the faster drug release in sink condition. As drug loading is decreased, high molecular weight polymers show better stability. However the drug release is governed by polymer dissolution.
Smruti P. Chaudhari and Rutesh H. Dave *
Director, Division of Pharmaceutical Sciences, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, New York, USA
06 May, 2016
06 September, 2016
23 September, 2016
01 October 2016