Solid dispersion in the development of a nimodipine delayed-release tablet formulation

Abstract

Nimodipine (NMD) is a dihydropyridine calcium channel blocker with selectivity for cerebral blood vessels and the major therapeutic indication of NMD is for the prevention and treatment of delayed ischemic neurological disorders and other cerebrovascular disorders, such as stroke which is associated with biological rhythm. This study was mainly designed to solve the drawback of conventional NMD solid dosage form, low bioavailability and limited clinical efficacy, by preparing enteric solid dispersion (SD) and the SD was prepared via melting method. The physical state of the dispersed NMD in the polymer matrix was characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and dissolution studies. Compared with pure drug and physical mixture, the dissolution of NMD-SD was enhanced dramatically (about 80%). Furthermore, in consideration of the biological rhythm of stroke, we first obtained a delayed-release tablet containing NMD-SD by a direct powder compression method. As shown in the dissolution studies, the tablet released less than 10% in the artificial gastric acid in the initial 2 h and released 32.1%, 75%, more than 90% at 4, 10 and 14 h respectively in the artificial intestinal fluid. This investigation has solved the problems of oral solid dosage forms of NMD, and it has the good industry prospect.

Keywords

• Nimodipine
• Solid dispersion
• Delayed-release
• Dissolution test