The objective of study was to develop and evaluate a stable lyophilized formulation of antihypertensive agent SNP4027. SNP4027 is a metabolite of arachidonic acid, is a naturally occurring prostaglandin with potent vasodilator activity and inhibitory activity of platelet aggregation. SNP4027 gets rapidly hydrolyzed at neutral pH in blood and is also subject to enzymatic degradation. SNP4027 is unstable at pH lower than 10.5, so stable bulk solution of formulation was prepared by adjusting pH at 13 with sodium hydroxide. Based on these preformulation observations, a lyophilized formulation containing 1.5 mg/ml of SNP4027 was prepared in a buffer solution of pH at 13. To minimize the degradation, 1N (4%) sodium hydroxide solution was included to prepare stable formulation. Rubber closures, filter membranes and liquid transfer tubing were selected on the basis of compatibility studies and absence of loss of drug due to adsorption of these components. The lyophilized formulation was reconstituted with 5 ml of sterile diluent for SNP4027 and subjected to accelerated and long term stability studies. Lyophilized formulation of SNP4027, when administered chronically, should be prepared in a drug delivery reservoir appropriate for the infusion pump with a total reservoir volume of at least 100 ml. Lyophilized formulation of SNP4027 should be prepared using 2 vials of sterile diluent for use during a 24 hour period without drug precipitation and degradation. Accelerated stability studies suggested that the product should be kept at 2�°C to 8�°C for long term storage.
Loading....