Ammar Hussein O, Ghorab Mahmoud, Kamel Rabab, Salama Alaa H
Department of Pharmaceutical Technology, National Research Center, Dokki, Cairo, Egypt.
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt, Cairo, Egypt.
Drug Deliv Transl Res. 2016 Jun;6(3):210-24. doi: 10.1007/s13346-016-0280-4.
This study is focused on the design of gastro-retentive drug delivery system composed of hollow microspheres (microballoons) for the sustained delivery of cinnarizine (CIN). The microballoons (MBs) were prepared by the emulsion solvent diffusion method using cellulose acetate butyrate (CAB) as the hosting polymer and absolute ethanol (ETH) and dichloromethane (DCM) as solvents. A 3(3) full factorial experimental design was adopted to study the effect of different variables and to find an optimum formula with desired properties. Prepared microballoons showed high drug loading capacities and controlled release behaviour. The optimum formulation was chosen on the basis of achieving maximum values for both drug loading capacity and release efficiency as well as having suitable size. The optimized MB (MB-F21) was composed of 200 mg CIN and 400 mg CAB with a DCM/ETH ratio of 2:1. Scanning electron microscopy for the optimum formulation showed a spherical outline with internal porous structure. An in vivo study using human volunteers was performed by determination of CIN concentration in the plasma using the liquid chromatography-mass spectrometry (LC-MS) method. Results proved the superiority of the designed formulation over the market product Stuval® tablets in bioavailability parameters comprising T max as well as area under the plasma CIN concentration-time curve (AUC0-24 h) and AUC0-∞ values. Also, the significantly greater value of mean residence time (MRT) in case of MB-F21 indicates its higher gastric residence time and proves the advantages of micro-multiparticulate dosage forms over conventional one.
本研究聚焦于由中空微球（微囊）组成的胃滞留药物递送系统的设计，用于桂利嗪（CIN）的持续递送。微囊（MBs）采用乳液溶剂扩散法制备，以醋酸丁酸纤维素（CAB）作为载体聚合物，无水乙醇（ETH）和二氯甲烷（DCM）作为溶剂。采用3（3）全因子实验设计来研究不同变量的影响，并找到具有所需特性的最佳配方。制备的微球显示出高载药量和控释行为。基于实现载药量和释放效率的最大值以及具有合适的尺寸来选择最佳配方。优化后的微囊（MB-F21）由200mg CIN和400mg CAB组成，DCM/ETH比例为2:1。最佳配方的扫描电子显微镜显示出具有内部多孔结构的球形轮廓。通过使用液相色谱-质谱（LC-MS）法测定血浆中CIN浓度，对人类志愿者进行了体内研究。结果证明，在包括达峰时间（T max）以及血浆CIN浓度-时间曲线下面积（AUC0-24 h）和AUC0-∞值等生物利用度参数方面，所设计的制剂优于市售产品Stuval®片。此外，MB-F21的平均驻留时间（MRT）显著更高，表明其胃滞留时间更长，并证明了微多颗粒剂型相对于传统剂型的优势。
