Improvement of photostability and dissolution profile of isradipine using inclusion complex

Abstract

Inclusion complexes using β-cyclodextrin were manufactured by solvent evaporation method. Then, sustained release (SR) hydroxypropylmethylcellulose (HPMC) matrix tablets containing inclusion complex were prepared via direct compression. Isradipine was chosen as a model drug due to its low solubility, photo-instability and short elimination half-life. The physicochemical properties of the inclusion complexes were examined using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The solubility test and dissolution behaviours were also investigated. Based on the solubility experiments, a 1:2 molar ratio (isradipine:β-Cyclodextrin) was best and chosen to prepare inclusion complexes. In addition, the crystal structure of isradipine was converted to an amorphous structure, as confirmed by Fourier transform infrared spectroscopy (FT-IR) and DSC. The photostability of isradipine in the inclusion complex was more stable than pure isradipine after 4 days radiation. By using hypromellose as the hydrophilic sustained release material, the dissolution rate was retarded during 24 h. A combined method of inclusion complex and SR technology showed increased and sustained release profile above that of Dynacirc® SR Cap. 5 mg.