- 學位論文
複方西他列汀與二甲雙胍持續釋放劑型開發
Development Combination of Sitagliptin/Metformin Extended-Release Dosage Form
摘要
從2011年到2015年，固定劑量組合(FDC)的批准數量有著逐漸增加的趨勢，然而在市售品上，能夠看到一個複方劑型具備兩種不同的藥物釋放速率，通常都是以包覆膜衣為主，其一種藥物通常溶於膜衣層中，另一種藥物存在核心層。在膜衣包覆的過程中，需要考量到停留在劑型上的膜衣其藥物是否適量及膜衣的完整性。因此，本研究將以各別使用不同方式之造粒，並將兩者混合打錠，使其具有各別且互不影響的釋放速率之複方錠劑。 本實驗分為兩種釋放速率之錠劑，一為西他列汀(Sitagliptin)並使用黏合劑Pharmacoat 606與崩散劑Croscamellose sodium讓其在短時間內釋放，另一為二甲雙胍(Metformin) 採用不同造粒方法與打錠壓力，並使用Metolose 60SH-50, Metolose 60SH-4000, Eudragit RS 30D, Compritol 888 ATO等多種不同控釋賦形劑，使其緩慢釋放。選定處方S3與F13將其打錠形成複方Sitagliptin/Metformin，並與市售品進行溶離相似性分析。 實驗結果顯示，當速放劑型內含有黏合劑時，崩散劑的使用量很重要之外，黏合劑的使用量也需要考量到。含有與Compritol 888 ATO類似的疏水性間質需經過熱處理才有緩釋效果，且會隨著顆粒間緊密的程度影響藥物釋放。
並列摘要
From 2011 to 2015, the number of FDC approved gradually increased. However, on the market, it can be seen that a compound dosage form has two different drug release rates, usually coated with film coating. In the process of film coating, it is necessary to consider whether the the drug in film coating solution stays on the dosage form appropriately and the integrity of the film. Therefore, this study will use different methods of granulation separately, and mix the two into tablets which one is immediately release, another is extant release. This experiment is divided into two release rate tablets, one is Sitagliptin and uses the binder Pharmacoat 606 and the disintegrant Croscamellose sodium to release it in a short time. The other is that metformin uses different granulation methods and tablet pressures, and uses Metolose 60SH-50, Metolose 60SH-4000, Eudragit RS 30D, Compritol 888 ATO to make it release slowly. The S3 and F13 were selected to form Sitagliptin/metformin tablet and compared with the commercial products. The experimental results show that when the immediately-release dosage form which contains the binder, the amount of disintegrating powder is important, and the amount of binder also needs to be considered. Containing hydrophobic interstitial similar to Compritol 888 ATO requires heat treatment to have a sustained release effect, and affect the release of the drug as the particles are tightly packed.