Controlled poorly soluble drug release from solid self-microemulsifying formulations with high viscosity hydroxypropylmethylcellulose

• Published in: European journal of pharmaceutical sciences 2008-08, Vol.34 (4), p.274-280
• Main Authors: Yi, Tao, Wan, Jiangling, Xu, Huibi, Yang, Xiangliang
• Format: Article
• Language: English
• Subjects: Administration, Oral; Biological and medical sciences; Calcium Channel Blockers - administration & dosage; Calcium Channel Blockers - chemistry; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Controlled release; Crystallography, X-Ray; Delayed-Action Preparations; Diffusion; Drug Carriers; Drug Compounding; Emulsions; General pharmacology; Glycerides; Hydroxypropylmethylcellulose; Hypromellose Derivatives; Kinetics; Lipids - chemistry; Medical sciences; Methylcellulose - analogs & derivatives; Methylcellulose - chemistry; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Nimodipine - administration & dosage; Nimodipine - chemistry; Oleic Acids - chemistry; Organic Chemicals - chemistry; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyethylene Glycols - chemistry; Poorly soluble drugs; Powder Diffraction; Self-microemulsifying; Solubility; Spray drying; Surface Properties; Technology, Pharmaceutical - methods; Viscosity
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2008.04.010

The objective of this work was the development of a controlled release system based on self-microemulsifying mixture aimed for oral delivery of poorly water-soluble drugs. HPMC-based particle formulations were prepared by spray drying containing a model drug (nimodipine) of low water solubility and hydroxypropylmethylcellulose (HPMC) of high viscosity. One type of formulations contained nimodipine mixed with HPMC and the other type of formulations contained HPMC and nimodipine dissolved in a self-microemulsifying system (SMES) consisting of ethyl oleate, Cremophor ® RH 40 and Labrasol ®. Based on investigation by transmission electron microscopy (TEM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction, differences were found in the particle structure between both types of formulations. In vitro release was performed and characterized by the power law. Nimodipine release from both types of formulations showed a controlled release profile and the two power law parameters, n and K, correlated to the viscosity of HPMC. The parameters were also influenced by the presence of SMES. For the controlled release solid SMES, oil droplets containing dissolved nimodipine diffused out of HPMC matrices following exposure to aqueous media. Thus, it is possible to control the in vitro release of poorly soluble drugs from solid oral dosage forms containing SMES.