Sarkar Srimanta, Ooi Shing Ming, Liew Celine Valeria, Tan Bing Xun, Heng Paul Wan Sia
GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy, National University of Singapore, 18 Science Drive, 117543, Singapore.
GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy, National University of Singapore, 18 Science Drive, 117543, Singapore.
Int J Pharm. 2014 Nov 20;475(1-2):558-65. doi: 10.1016/j.ijpharm.2014.09.004. Epub 2014 Sep 8.
This study investigated the influence of different disintegrants, present in different substrate physical forms, on dimensional recovery of multi-component tablets prepared at different compression pressures. Formulations containing model drug, metformin, (10%, w/w), different disintegrants (10%, w/w), and lactose (80%, w/w) were compressed directly or after granulation using polyvinyl pyrrolidone (1%, w/w) as binder, into tablets (350 mg, 10mm diameter) at 150, 200, and 250 N/mm(2) compression pressures. Tablets were characterized for immediate dimensional recovery (IR) after ejection from the die, latent dimensional recovery (LR) over 24 h, tensile strength, and disintegration. The IR was predominantly contributed by crystalline components whereas LR was brought about by polymeric materials. With increased compression pressure, higher degree of plastic deformation of the polymeric disintegrants resulted in tablet with lower LR and higher tensile strength. Presence of polyvinyl pyrrolidone in the granules contributed considerably to plastic deformation, and the tablets produced had lower LR, higher tensile strength, and longer disintegration time. This study indicated that use of granules as the feed substrate physical form and a prudent selection of components may enable the coating of resultant tablets immediately after compression without the risk of coat damage due to LR.
本研究考察了存在于不同底物物理形态中的不同崩解剂,对在不同压缩压力下制备的多组分片剂尺寸恢复的影响。含有模型药物二甲双胍(10%,w/w)、不同崩解剂(10%,w/w)和乳糖(80%,w/w)的制剂,直接压片或在制粒后,使用聚乙烯吡咯烷酮(1%,w/w)作为粘合剂,在150、200和250 N/mm(2)的压缩压力下压制成片剂(350 mg,直径10mm)。对片剂进行了表征,包括出模后的即时尺寸恢复(IR)、24小时内的潜在尺寸恢复(LR)、抗张强度和崩解情况。IR主要由结晶成分引起,而LR则由聚合物材料导致。随着压缩压力的增加,聚合物崩解剂更高程度的塑性变形导致片剂的LR降低和抗张强度升高。颗粒中聚乙烯吡咯烷酮的存在对塑性变形有很大贡献,所生产的片剂具有较低的LR、较高的抗张强度和较长的崩解时间。本研究表明,使用颗粒作为进料底物物理形态并谨慎选择成分,可能使压制后的片剂能够立即包衣,而不会因LR导致包衣受损。