DESIGN AND INVITRO EVALUATION OF SLOW-RELEASE DOSAGE FORM OF PIRETANIDE - UTILITY OF BETA-CYCLODEXTRIN - CELLULOSE DERIVATIVE COMBINATION AS A MODIFIED-RELEASE DRUG CARRIER

To modify the release rate of piretanide, a potent loop diuretic, a double‐layer tablet was designed, and in vitro release was evaluated. For a rapidly releasing portion, hydrophilic β‐cyclodextrin derivatives were employed to form a water‐soluble complex with piretanide. For a sustained‐release portion, cellulose derivatives were used to provide appropriate hydrophobicity. The release rate of piretanide in the pH range 1.2–6.8 was automatically monitored by a pH‐changeable dissolution testing apparatus. The low solubility of piretanide in acidic medium was significantly improved by complexations with dimethyl‐β‐cyclodextrin (DM‐β‐CyD) and hydroxypropyl‐β‐cyclodextrin (HP‐β‐CyD). The pH‐independent slow release was attained by use of hydroxypropylcellulose (HPC):ethylcellulose (EC) matrices. Then, an optimal formulation of a double‐layer tablet was obtained by the combination of each fraction. For example, the tablet consisting of the [DM‐β‐CyD/(HPC:EC)] system in the weight ratio [1/3(1:3)] provided a sufficiently slow release of the drug over a period of 8 h in a wide pH region following an initial rapid dissolution. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company