FORMULATION OPTIMIZATION OF IMMEDIATE RELEASE BILAYER TABLETS OF TELMISARTAN AND HYDROCHLOROTHIAZIDEAbstract
The aim of the current investigation was to develop bilayered immediate-release tablets of Telmisartan (TEL) and Hydrochlorothiazide (HCTZ) for the treatment of hypertension. In contrast to monotherapy, the dual drug therapy of TEL (an angiotensin II receptor blocker) and HCTZ (diuretic) is connoted to have a cumulative antihypertensive effect. Additionally, it offers ameliorative patient adherence to fixed-dose combination therapy over monotherapy and diminishes pill burden and dose-related side effects. The preformulation studies were accomplished by determining the compatibility of model drugs with their respective excipients by FTIR studies. These studies unambiguously connoted nix chemical interaction of excipients with the chosen model drugs. The formulation development was achieved in phases comprising of preliminary screening, pre-optimization and optimization studies. The wet granulation technique was adopted for formulating bilayer tablets. For pre-optimization studies, five batches for each layer (T1-T5 for TEL and H1-H5 for HCTZ layer) were prepared. Based on the outcomes of pre-optimization, the formulation batches T2 and H5 were subsequently chosen for optimizing the varied process and formulation variables. The optimum bilayer formulation (T2H5) released drugs within 1 h (TEL-102.03% and HCTZ-101.03%) with individual layers. The super disintegrates attributing optimum immediate release characteristics were crospovidone (3.7% w/w) in TEL layer and sodium starch glycolate (1.66% w/w) in the HCTZ layer, respectively. The stability studies in conformity to ICH guidelines revealed a shelf life of 20 months. The study concluded that the bilayer tablets of TEL and HCTZ could be an alternative to a conventional dosage form for the treatment of hypertension.