Dissolution and Solid-State Characterization of Poorly Water-Soluble Drugs in the Presence of a Hydrophilic Carrier

• Published in: AAPS PharmSciTech Vol. 12; no. 4; pp. 1227 - 1233
• Main Authors: Talukder, Rahmat, Reed, Chase, Dürig, Thomas, Hussain, Muhammad
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.12.2011
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Calorimetry, Differential Scanning; Carbamazepine - chemistry; Cellulose - analogs & derivatives; Cellulose - chemistry; Chemistry, Pharmaceutical; Crystallization; Crystallography, X-Ray; Drug Carriers; Drug Compounding; Hydrophobic and Hydrophilic Interactions; Ibuprofen - chemistry; Indexing in process; Kinetics; Molecular Weight; Nifedipine - chemistry; Pharmacology/Toxicology; Pharmacy; Research Article; Solubility; Technology, Pharmaceutical - methods; Wettability; wettability; HPC; hydrophilic carrier; dissolution enhancement
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-011-9697-8

The aim of this study was to investigate the effects of a hydrophilic carrier on the solid-state and dissolution characteristics of poorly water-soluble drugs. Three poorly water-soluble drugs, ibuprofen, carbamazepine, and nifedipine, were studied in combination with hydroxypropyl cellulose (HPC), a low molecular weight hydrophilic polymer, without the use of solvent. A 1:1 drug–polymer ratio was used to evaluate the percent drug release, crystallinity, and wettability. A drug–polymer ratio of 1:4 was also used in co-grinding process to evaluate the effect of polymer levels on drug release. Dissolution studies were carried out in deionized water. Mean dissolution time (MDT) was calculated, and statistical analysis of MDTs was done following a single factor one-way analysis of variance. The dissolution rate of the drugs was enhanced by several folds by the simple process of co-grinding with HPC. X-ray diffraction studies were done to investigate the effects of physical and co-ground mix with HPC on the crystallinity of the drugs, which indicated a partial loss in crystallinity upon grinding. Differential scanning calorimetry studies were performed in order to identify possible solid-state interactions between the respective drugs and HPC. Wettability of the drugs by a 0.5% aqueous HPC solution was compared with that of water and n -hexane using the “Washburn method.” Increased wetting and hydrophilization of the drugs by HPC, enlarged surface area due to particle size reduction, and a decrease in the degree of crystallinity were identified as the likely contributors to dissolution rate enhancement.