Formulation and development of Bi-layer solid dosage form of Losartan potassium containing an immediate release layer and a slow release layer

Abstract

Losartan potassium (LP) is a type of medicine called an Angiotensin II receptor antagonist. It works by preventing the action of a hormone in the body called angiotensin II. Angiotensin II normally acts on special receptors in the body, with two main results. It causes the peripheral blood vessels to narrow, and it also stimulates the production of another hormone called aldosterone. Aldosterone causes salt and water to be retained by the kidneys, which increases the volume of fluid in the blood vessels. LP blocks the receptors that angiotensin II acts on, and so prevents its actions. The main result of this is that the peripheral blood vessels are allowed to widen, which means that there is more space and less resistance in these blood vessels. This helps lower blood pressure. The present invention comprises a pharmaceutical solid dosage form having a first layer with an immediate release property and a second layer with a sustained release property. Each of these layers contains LP, with the ratio of the LP in the first layer to the second layer being in the range of from about 10:90 to about 12:88 by weight. Another aspect of the present invention is a method of treatment comprising administering to a patient in need thereof pharmaceutical solid dosages form wherein the total amount of LP is available in a therapeutic level for longer period. Method of formulation is divided in three major stages. Stage I: LP is encapsulated into Eudragit RS 100 (ERS) and Eudragit RL 100 (ERL) microspheres. The microspheres were prepared using solvent evaporation technique with an ultimate aim of prolonging drug release. Six formulations were prepared using different drug/polymer ratio. The effects of polymer type and polymer/ drug ratios on the size, surface morphology, encapsulation efficiency and the release characteristics of the microspheres were examined.