Formulation and development of fixed dose combination of antihypertensive and antidiabetic agent for treatment of co-existent type two diabetes mellitus and hypertension

Abstract

Objective: Coexistent Type Two Diabetes Mellitus (TTDM) and hypertension exposes patients to severe co-morbidities. Complex polypharmacy suggested by international organizations leads to the increased pill burden and decreased patient compliance which leads to worsening of conditions. Materials and Methods: Present research aims at the formulation and development of fixed dose combination (FDC) for treatment of coexistent hypertension and TTDM as it will help in increasing patient compliance. Literature survey and patient survey facilitated the selection of metformin HCl, telmisartan, atorvastatin and aspirin for the formulation of FDC. Formulation and development of enteric coated aspirin tablet and the bilayer tablet of metformin HCl, telmisartan & atorvastatin calcium were two major parts of this research.Aspirin was enteric coated by compression coating technique to avoid gastric irritation. Bilayer tablet separating metformin HCl layer from the layer of a mixture of telmisartan and atorvastatin calcium was prepared to avoid the physical incompatibility problem between metformin HCl and telmisartan. The final FDC formulation was prepared by encapsulating, enteric coated aspirin tablet and bilayer tablet in a size 00 capsule and subjected to accelerated stability studies. Results: Batch F2 of bilayer tablet containing one layer of metformin HCl and the other layer having a mixture of telmisartan& atorvastatin calcium releases more than 80% of metformin HCl, telmisartan and atorvastatin calcium within 1 hour. Batch A2E of enteric coated aspirin tablet was found to show delayed and complete drug release as compared to A2D within 3.5 hours. Similarity factor f2 was found to be 69.33. After long term storage of formulation at 40oC/75% RH, stability of drug components remained unaffected. Conclusion: FDC of antihypertensive and antidiabetic agent will be revolutionary in the treatment of coexistent TTDM and hypertension as it will be a cheaper alternative to current therapy.