Chem. Pharm. Bull. 53(10) 1240—1245 (2005)

drawbacks, such as increasing the dosage, the administration frequency and the resultant occurrence of side effects. Furthermore, as the rate-limiting step in the absorption process for poorly water-soluble drugs is the dissolution rate of such drugs in the gastrointestinal fluids rather than the rapidity of their diffusion across the gut wall, it is important to improve the oral bioavailability of poorly water-soluble drugs by improving their dissolution rate and solubility. This remains one of the most challenging aspects of drug development. The solid dispersion (SD) method, by which a drug is dispersed in a carrier to make it amorphous, is one of the pharmaceutical approaches most commonly employed to enhance bioavailability of poorly water-soluble drugs. Various pharmaceutical approaches for the preparation of SDs, including coprecipitation, lyophilization, spray drying, solvent evaporation, fusion and powder mixing methods, have been reported. An important mechanism is the reduction of the drug’s particle size to the microcrystalline or molecular level for rapid dissolution and absorption. Broadly speaking, there are three methods of preparing SDs; namely, the fusion method, the solvent process and a combination of these. However, the fusion method and solvent method have a number of drawbacks. The fusion method requires a high temperature which may result in the decomposition of the drugs, and furthermore, tacky or glassy solids may cause undesirable processing problems. In the solvent method, environmental concerns regarding solvent emissions and heath concerns regarding residual solvent make it necessary to restrict the use of organic solvent. A heating/pressurization/kneading/extruding method using a twin screw extruder is one of the methods proposed for this purpose. This extruder, originally designed as an extraction/casting device for polymer alloys in the plastic industry, is now used to process cereals and “functionalize” food materials, such as tissue products from animal protein. This device has already been used successfully to prepare SDs of nifedipine and hydroxypropylmethylcellulosephthalate (HPMCP), itraconazole and hydroxypropylmethylcellulose (HPMC), itraconazole and hydroxypropyl-betacyclodextrin (HP-beta-CD) to improve the solubility and dissolution properties of poorly water-soluble drugs. Six et al. prepared SDs of itraconazole-Eudragit E100/ PVPVA64 and found that the combination of the two polymers provides an SD with good dissolution properties and improved physical stability compared with the binary SDs of itraconazole. Kinoshita et al. prepared SDs of TAS-301, a poorly water-soluble drug, and a porous calcium silicate (FLR) using the twin screw extruder method. The solubility and bioavailability of TAS-301 were markedly enhanced by its melt-adsorption on FLR. These findings suggest that the twin screw extruder method is a useful technique for preparing SDs and improving the solubility and bioavailability of poorly water-soluble drugs. One of its advantages is that there is no need for the use of organic solvents during the process of preparation. Moreover, SDs can be produced at a lower temperature than the melting point of the drug and the softening temperature of the polymer, preventing the decomposition of the drug and carriers. In addition, various combinations of carriers can be employed to prepare SDs with improved dissolution and physical stability properties than the binary SDs. Nitrendipine (NIT) is a dihydropyridine calcium channel blocking agent producing peripheral vasodilation as its predominant in vivo effect. The molecular structure of NIT is illustrated in Fig. 1. NIT shares a common dihydropyridine nucleus with the calcium antagonist, nifedipine. Like nifedipine, NIT is used to treat a variety of cardiovascular disorders, such as angina pectoris and hypertension. NIT exists in the form of yellow crystals with a melting point of 156—159 °C. Due to its low aqueous solubility (about 2 mg/ml), leading to the poor absorption of NIT after oral administration, NIT