Belayneh Anteneh, Molla Fantahun, Kahsay Getu
Department of Pharmacy, College of Health Sciences, Debre Markos University, Debre Markos, Ethiopia.
Department of Pharmaceutics, School of Pharmacy, College of Health Sciences, Mekelle University, Mekelle, Ethiopia.
Adv Pharmacol Pharm Sci. 2020 Feb 18;2020:3546597. doi: 10.1155/2020/3546597. eCollection 2020.
The treatment of type II DM involves the use of combination of drugs, especially at the chronic stage. However, the pill burden of this combination therapy combined with swallowing difficulties, occurring at a later stage of DM, has been the major challenge for successful treatment outcomes. This study was aimed at formulating and optimizing a monolithic fixed-dose combination (FDC) of metformin (MET) and glibenclamide (GLB) orodispersible tablets (ODTs) to overcome both the pill burden and swallowing problems. The FDC ODTs were prepared by the melt granulation technique using polyethylene glycol (PEG) 6000 as a binding agent and crospovidone as a superdisintegrant. In the preliminary study, the effects of sodium lauryl sulphate (SLS), PEG 6000, crospovidone, and compression force on friability, disintegration time, and drug release of tablets were investigated. The FT-IR studies showed that there were no incompatibilities between MET and GLB as well as within excipients. The preliminary studies revealed that PEG 6000 and compression force significantly affect both the friability and the disintegration time, while SLS and crospovidone only affect the disintegration time. Therefore, the effects of PEG 6000, crospovidone, and compression force were further studied and optimized using the central composite design. Accordingly, the most desirable optimal values were obtained at 3.82% of PEG 6000, 9.83% of crospovidone, and 10.6 kN compression force having a friability of 0.302% and a disintegration time of 18.7 seconds. From these results, it can be concluded that a monolithic FDC of MET and GLB ODTs having adequate mechanical strength and faster disintegration time was successfully formulated.
II型糖尿病的治疗涉及联合用药，尤其是在慢性阶段。然而，这种联合治疗的药片负担，再加上糖尿病后期出现的吞咽困难，一直是成功治疗结果的主要挑战。本研究旨在制备并优化二甲双胍（MET）和格列本脲（GLB）的单片固定剂量复方（FDC）口腔崩解片（ODT），以克服药片负担和吞咽问题。采用熔融制粒技术，以聚乙二醇（PEG）6000作为黏合剂、交联聚维酮作为超级崩解剂制备FDC ODT。在初步研究中，考察了十二烷基硫酸钠（SLS）、PEG 6000、交联聚维酮和压片力对片剂脆碎度、崩解时间和药物释放的影响。傅里叶变换红外光谱（FT-IR）研究表明，MET与GLB之间以及辅料内部均不存在不相容性。初步研究表明，PEG 6000和压片力对脆碎度和崩解时间均有显著影响，而SLS和交联聚维酮仅影响崩解时间。因此，采用中心复合设计进一步研究并优化了PEG 6000、交联聚维酮和压片力的影响。据此，在PEG 6000含量为3.82%、交联聚维酮含量为9.83%、压片力为10.6 kN时获得了最理想的优化值，脆碎度为0.302%，崩解时间为18.7秒。从这些结果可以得出结论，成功制备了具有足够机械强度和更快崩解时间的MET与GLB ODT单片FDC。
