Zidan Ahmed S, Emam Sherif E, Shehata Tamer M, Ghazy Fakhr-eldin S
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt,
AAPS PharmSciTech. 2015 Jun;16(3):645-55. doi: 10.1208/s12249-014-0250-4. Epub 2014 Dec 11.
Pharmaceutical development was adopted in the current study to propose a pediatric rectal formulation of sulpiride as a substitute to the available oral or parenteral formulations in the management of Tourette syndrome (TS). The goal was to formulate a product that is easy to use, stable, and highly bioavailable and to achieve a rapid clinical efficacy. Towards this aim, sulpiride solid dispersion (SD) with tartaric acid at a weight ratio of 1:0.25 was incorporated into different suppository bases, namely witepsol W25, witepsol H15, witepsol E75, suppocire NA, suppocire A, glycerogelatin, and polyethylene glycols. The formulae were evaluated in vitro using different pharmacotechnical methods such as visual, melting, weight and content uniformities, drug release, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), and X-ray diffraction (XRD) analyses. In vivo bioavailability was also assessed in rabbits to compare the bioavailability of either raw sulpiride-incorporated or its SD-incorporated witepsol H15-based suppositories to its oral suspension (reference). Sulpiride SD-incorporated witepsol H15 formulation showed acceptable in vitro characteristics with a bioavailability of 117% relative to oral dosing, which excel that in humans (27% after dosing of oral product). In addition, the proposed formula not only passed the 6-month stability study but also proposed a promising scale-up approach. Hence, it showed a great potential for pediatric product development to manage TS in rural areas.
本研究采用药物研发方法,旨在提出一种舒必利的儿科直肠制剂,以替代目前用于治疗抽动秽语综合征(TS)的口服或肠胃外制剂。目标是制备一种易于使用、稳定且生物利用度高的产品,并实现快速的临床疗效。为此,将重量比为1:0.25的舒必利与酒石酸的固体分散体(SD)加入到不同的栓剂基质中,即半合成脂肪酸甘油酯W25、半合成脂肪酸甘油酯H15、半合成脂肪酸甘油酯E75、栓剂基质NA、栓剂基质A、明胶甘油和聚乙二醇。使用不同的药学技术方法对配方进行体外评估,如外观、熔点、重量和含量均匀度、药物释放、差示扫描量热法(DSC)、傅里叶变换红外光谱(FTIR)和X射线衍射(XRD)分析。还在兔子体内评估了生物利用度,以比较含舒必利原料药或其SD的半合成脂肪酸甘油酯H15基栓剂与口服混悬液(参比制剂)的生物利用度。含舒必利SD的半合成脂肪酸甘油酯H15制剂显示出可接受的体外特性,相对于口服给药,生物利用度为117%,优于人体中的生物利用度(口服产品给药后为27%)。此外,所提出的配方不仅通过了6个月的稳定性研究,还提出了一种有前景的放大方法。因此,它在农村地区开发用于治疗TS的儿科产品方面显示出巨大潜力。