Development of oral self-emulsifying drug delivery systems valsartan and in vitro-in vivo evaluation

Many cardiovasculer diseases have been resulted from high blood pressure. Especially in endustrized countries for disability and early death high blood pressure is one of the biggest risk factor. Therefore, antihypertensive treatment reduce the risk of cardiovasculer complications in patients with high mortality with hypertension. Valsartan is an orally active antihypertensive drug with high mortality with high selectivity and included in angiotensin II type I receptor antagonist group. The affinity of Valsartan for angiotensin II tip I receptor is about 20000 fold greater than its affinity for angiotensin II tip II receptor. This loosed the blood vessels and decreases blood pressure. Valsartan rapidly absorbed after oral administration but oral bioavailability is 25% because of its inadequate and unbalanced bioavailability. It is absorbed from the upper part of the gastrointestinal tract and it is less soluble in this region because of its acidic environment. Also Valsartan exposed to first pass metabolism in liver and its bioavailability decreases with food. Many studies have been made in the literature in order to achieve the low solubility and bioavailability problem of Valsartan. These include solid dispersions, cyclodextrin complexes, microcapsule formulations, self emulsifying systems. In this project, different lipid-based drug delivery systems of valsartan will be developed and these formulations compared within each other. As a result, an ideal drug delivery system for valsartan with low solubility and bioavailability will be recommended. As is known, valsartan is used in increasing doses in treatment of hypertension alone, and it is used in combination products when treatment is insufficient. However, according to today's health precautions, antihypertensive combination forms are prescribed as a last solution. For this reason, it is very important that valsartan, which has high selectivity and high drug market share, is reformulated with an innovative formulation to overcome the problem of bioavailability. Thus, with this new formulation, it will be possible for patients to increase their treatment tolerance and reduce the requirement of combined formulations containing valsartan, thereby reducing drug consumption and contributing positively to the health expenses.