Manufacture of a Fixed Dose Combination Product for the Treatment of Type II Diabetes by Hot Melt Continuous Granulation

Type II diabetes mellitus is a preventable worldwide health issue affecting an ever-increasing proportion of the global population. The latest figures published by the World Health Organisation (WHO) indicate that the current worldwide number of people with diabetes is 422 million as of 2014, up from 108 million in 1980. This represents an increase in the prevalence of the disease in the same time period from 4.7% to 8.5%1. More worryingly, by 2040 it is estimated that 642 million people worldwide will be affected by diabetes. As diabetes is considered to be a chronic illness, medication compliance plays a vital role. Fixed dose combination (FDC) products provide us with a strong basis to reduce the pill burden by simply combining several APIs into one convenient dosage unit form. Statistically, the risk of non-compliance to medication regimens is reduced by 24% - 26% with FDC products with solid oral dosage forms being most favoured due to ease of administration.The development of oral solid dosage forms, such as tablets, that contain a high dose of drug(s) requires polymers and other additives to be incorporated at as low levels as possible, to keep the final tablet weight low, and correspondingly the dosage form size small enough to be acceptable from a patient perspective. Additionally, a multi-step manufacturing process is usually required when manufacturing oral solid dosage forms. The purpose of this study is to develop and produce, by hot melt continuous granulation technology, a high-dose immediate release fixed dose combination product of metformin hydrochloride (MET) and sitagliptin (SIT), with drug loads of approximately 80 % w/w and 5 % w/w, respectively.