The preparation of enteric solid dispersions with hydroxypropylmethylcellulose acetate succinate using a twin-screw extruder

Abstract

Hydroxypropylmethylcellulose acetate succinate (HPMCAS) has a ductile nature at ca. 130°C and can be readily extruded with a twin-screw extruder. It was found that dissolved HPMCAS retarded the crystallization of nifedipine (NP) in an aqueous medium compared with hydroxypropylmethylcellulose phthalate (HPMCP) and was a suitable carrier for preparing NP solid dispersions. Three weight ratios of the mixtures of NP and HPMCAS (1:1, 1:3, 1:5) were extruded with a twin-screw extruder. At a weight ratio of 1:5, crystalline peaks of NP observed in the physical mixture were not detected by powder X-ray diffractometry and differential scanning calorimetry (DSC). In an alkali medium, the concentration of dissolved NP increased and was maintained. Similarly, indomethacin (IM), nicardipine hydrochloride and oxybutynin hydrochloride with HPMCAS (weight ratio 1:5) were extruded. There were no crystalline peaks of each drug in the powder X-ray diffractometry and DSC scans. Also, the dissolution of IM was improved by extrusion. These results show that HPMCAS can be used to improve the dissolution of poorly water-soluble compounds and a twin-screw extruder is useful for efficiently preparing a solid dispersion.