Kumar Smiti, Chawla Garima, Bansal Arvind K
Department of Pharmaceutical Technology Formulations, National Institute of Pharmaceutical Education and Research, Nagar, Punjab, India.
Pharm Dev Technol. 2008;13(6):559-68. doi: 10.1080/10837450802310180.
Spherical crystallization technique combines crystallization and agglomeration directly to generate spherical crystals with improved micromeretic properties, thus obviating need for further processing by granulation and agglomeration. The present study was focused on spherical crystallization of an antihelmentic drug - Mebendazole (MBZ) - using spherical agglomeration technique. Apart from being poorly water-soluble, MBZ exhibits poor flow and compressibility owing to its needle shaped crystal habit and electrostatic charge. Spherical agglomeration was carried out in the presence of different bridging liquids (hexane, octanol, toluene, dichloromethane) and polymers (polyethylene glycol, cross-povidone, starch, cross carmellose sodium, hydroxyl propyl methyl cellulose (HPMC), hydroxyl propyl cellulose (HPC), ethyl cellulose (EC), Eudragit S100, Eudragit RLPO, Eudragit RD100, Eudragit E), by employing different crystallization conditions such as variation of polymer type, polymer concentration, and rate of stirring. The final parameters were optimized to obtain crystals with an aspect ratio in the range of 1-2 compared to a value of 12 for untreated MBZ. These agglomerates retained form C of MBZ, and exhibited good flow properties, high bulk density and improved compressibility. Lower elastic:plastic energy (EE/PE) ratio for spherical crystals generated in the presence of Eudragit-S100 and Hydroxypropylcellulose (HPC) indicated better compressibilty of spherical crystals.
球形结晶技术直接将结晶和团聚结合起来，生成具有改善的粉体学性质的球形晶体，从而无需通过制粒和团聚进行进一步加工。本研究聚焦于使用球形团聚技术对一种抗蠕虫药物——甲苯达唑（MBZ）进行球形结晶。除了水溶性差之外，MBZ由于其针状晶习和静电荷而表现出不良的流动性和可压性。在不同的架桥液（己烷、辛醇、甲苯、二氯甲烷）和聚合物（聚乙二醇、交联聚维酮、淀粉、交联羧甲基纤维素钠（交联羧甲纤维素钠）、羟丙基甲基纤维素（HPMC）、羟丙基纤维素（HPC）、乙基纤维素（EC）、丙烯酸树脂S100、丙烯酸树脂RLPO、丙烯酸树脂RD100、丙烯酸树脂E）存在的情况下，通过采用不同的结晶条件，如聚合物类型、聚合物浓度和搅拌速率的变化，进行球形团聚。优化最终参数以获得长径比在1 - 2范围内的晶体，而未处理的MBZ的长径比值为12。这些团聚体保留了MBZ的晶型C，并表现出良好的流动性能、高堆密度和改善的可压性。在丙烯酸树脂S100和羟丙基纤维素（HPC）存在下生成的球形晶体的较低弹性：塑性能量（EE/PE）比表明球形晶体具有更好的可压性。
