Low-Viscosity Hydroxypropylcellulose (HPC) Grades SL and SSL: Versatile Pharmaceutical Polymers for Dissolution Enhancem
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Research Article Low-Viscosity Hydroxypropylcellulose (HPC) Grades SL and SSL: Versatile Pharmaceutical Polymers for Dissolution Enhancement, Controlled Release, and Pharmaceutical Processing Ashish Sarode,1,2 Peng Wang,1,2 Catherine Cote,3 and David R. Worthen1,2,4
Received 13 July 2012; accepted 9 November 2012; published online 19 December 2012 Abstract. Hydroxypropylcellulose (HPC)-SL and -SSL, low-viscosity hydroxypropylcellulose polymers, are versatile pharmaceutical excipients. The utility of HPC polymers was assessed for both dissolution enhancement and sustained release of pharmaceutical drugs using various processing techniques. The BCS class II drugs carbamazepine (CBZ), hydrochlorthiazide, and phenytoin (PHT) were hot melt mixed (HMM) with various polymers. PHT formulations produced by solvent evaporation (SE) and ball milling (BM) were prepared using HPC-SSL. HMM formulations of BCS class I chlorpheniramine maleate (CPM) were prepared using HPC-SL and -SSL. These solid dispersions (SDs) manufactured using different processes were evaluated for amorphous transformation and dissolution characteristics. Drug degradation because of HMM processing was also assessed. Amorphous conversion using HMM could be achieved only for relatively low-melting CBZ and CPM. SE and BM did not produce amorphous SDs of PHT using HPC-SSL. Chemical stability of all the drugs was maintained using HPC during the HMM process. Dissolution enhancement was observed in HPC-based HMMs and compared well to other polymers. The dissolution enhancement of PHT was in the order of SE>BM>HMM>physical mixtures, as compared to the pure drug, perhaps due to more intimate mixing that occurred during SE and BM than in HMM. Dissolution of CPM could be significantly sustained in simulated gastric and intestinal fluids using HPC polymers. These studies revealed that low-viscosity HPC-SL and -SSL can be employed to produce chemically stable SDs of poorly as well as highly water-soluble drugs using various pharmaceutical processes in order to control drug dissolution. KEY WORDS: controlled release formulations; hydroxypropylcellulose; melt extrusion; solid dispersion.
INTRODUCTION The biopharmaceutical classification system (BCS) categorizes active pharmaceutical ingredients (APIs) into four classes based upon their aqueous solubility and gastrointestinal permeability (1). According to the BCS, class II compounds exhibit low solubility and high permeability due to their crystalline hydrophobic characteristics which result in poor bioavailability after oral administration (2). BCS class I drugs are both highly soluble and permeable, and often require frequent administration due to their rapid elimination in order to maintain therapeutic blood levels, which may lead to poor patient compliance (3). Over 40% of the new chemical entities that are being discovered today by high-throughput screening and combinatorial chemistry fall into the BCS class II category (4). Various techniques, such as particle size re1
Department of Biomedical and Pharmaceutical
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