Abstract： Commercially available domperidone -a D2 receptor antagonist- is an immediate release formulation which has never been formulated into microspheres for sustained release. The present work aims towards study...Abstract： Commercially available domperidone -a D2 receptor antagonist- is an immediate release formulation which has never been formulated into microspheres for sustained release. The present work aims towards studying the effect of combination of a natural chitosan from an oyster shell of Mystilis edulis and HPMC （hydroxy propyl methyl cellulose） （spectracel 15 E） as polymer and tripolyphosphate as cross linking agent using wet gelation technique. The various polymer combination ratios for different batches were compared with a low molecular weight standard chitosan. The extracted chitosan - HPMC polymer combination ratios were chosen at ten levels： as batches B1, B2, B3, B4, B5, B6, B7, B8, B9, B10 for 1：1, 1：2, 2：1, 1：0, 0：1, 3：1, 1：3, 5：1, and 1：5 and 1：1 having 450：450, 300：600, 600：300, 900：0, 0：900, 675：225, 225：675, 750：150, 150：750, 450：450 mg respectively, while the quantity of domperidone and tripolyphosphate remained constant. B 11 and B 12 were formulated with standard chitosan and HPMC. The percentage yield of the formulated microspheres was determined and then evaluated for flowability, drug entrapment efficiency, drug release and mechanism of drug release by Fickian diffusion. The best batches of the domperidone loaded microspheres produced from the combination polymer were compared with the standard chitosan. The highest yields of microspheres were given by batches B12, B11, B10, and B4 with values of 50.1 ± 0.1%, 49.6 ± 0.1%, 46.6 ：± 0.1%, and 46.1 ± 0.0% respectively while the lowest yield were 23.3 ± 0.2% and 23.6 ± 0.2%. B5 and B6 and B9 did not yield any microsphere. The bulk density, tapped density, compressibility and Hausner＇s ratio of the microspheres showed good flowability and high percent compressibility. The drug entrapment efficiency showed that the entrapment ranged from 54.2 to 97.2, where the least entrapment was B4 （54.2 ± 0.1） and the highest B12 （97.2 ± 0.2）. The polymer surface of the microspheres as observed by SEM （scanning electron microscopy） was heterogeneous and porous which offers enhanced bioadhesivity. The dissolution study was used to determine the percentage drug release which ranged from 12.1% to 68.9% after 5 hours. Batches 1, 2, 3, 4, 7, and I 1 follow zero order kinetics via Fickian diffusion. The results indicate that microspberes of domperidone could be successfully formulated with a natural chitosan either alone or in combination with HPMC for sustained delivery of domperidone. Furthermore, the concentration of the natural polymer and HPMC employed in the formulation need to be carefully selected to enable the production of microspheres with the desired sustained release properties.展开更多
文摘Abstract： Commercially available domperidone -a D2 receptor antagonist- is an immediate release formulation which has never been formulated into microspheres for sustained release. The present work aims towards studying the effect of combination of a natural chitosan from an oyster shell of Mystilis edulis and HPMC （hydroxy propyl methyl cellulose） （spectracel 15 E） as polymer and tripolyphosphate as cross linking agent using wet gelation technique. The various polymer combination ratios for different batches were compared with a low molecular weight standard chitosan. The extracted chitosan - HPMC polymer combination ratios were chosen at ten levels： as batches B1, B2, B3, B4, B5, B6, B7, B8, B9, B10 for 1：1, 1：2, 2：1, 1：0, 0：1, 3：1, 1：3, 5：1, and 1：5 and 1：1 having 450：450, 300：600, 600：300, 900：0, 0：900, 675：225, 225：675, 750：150, 150：750, 450：450 mg respectively, while the quantity of domperidone and tripolyphosphate remained constant. B 11 and B 12 were formulated with standard chitosan and HPMC. The percentage yield of the formulated microspheres was determined and then evaluated for flowability, drug entrapment efficiency, drug release and mechanism of drug release by Fickian diffusion. The best batches of the domperidone loaded microspheres produced from the combination polymer were compared with the standard chitosan. The highest yields of microspheres were given by batches B12, B11, B10, and B4 with values of 50.1 ± 0.1%, 49.6 ± 0.1%, 46.6 ：± 0.1%, and 46.1 ± 0.0% respectively while the lowest yield were 23.3 ± 0.2% and 23.6 ± 0.2%. B5 and B6 and B9 did not yield any microsphere. The bulk density, tapped density, compressibility and Hausner＇s ratio of the microspheres showed good flowability and high percent compressibility. The drug entrapment efficiency showed that the entrapment ranged from 54.2 to 97.2, where the least entrapment was B4 （54.2 ± 0.1） and the highest B12 （97.2 ± 0.2）. The polymer surface of the microspheres as observed by SEM （scanning electron microscopy） was heterogeneous and porous which offers enhanced bioadhesivity. The dissolution study was used to determine the percentage drug release which ranged from 12.1% to 68.9% after 5 hours. Batches 1, 2, 3, 4, 7, and I 1 follow zero order kinetics via Fickian diffusion. The results indicate that microspberes of domperidone could be successfully formulated with a natural chitosan either alone or in combination with HPMC for sustained delivery of domperidone. Furthermore, the concentration of the natural polymer and HPMC employed in the formulation need to be carefully selected to enable the production of microspheres with the desired sustained release properties.
