FORMULATION OF AN ORAL MODIFIED RELEASEDOSAGE FORM OF AN ADRENERGIC DRUG
Albuterol, a sympathomimetic amine is a potent selective Beta adrenergic agonist. As a result it is used as a bronchodilator to treat chronic obstructive airway diseases in adults and childrens. The drug has a short half-life of 3-4 hours and must be administered 3-4 times daily to maintain a therapeutic concentration. This investigation was undertaken to study the in-vitro drug release characteristics of the marketed product under conditions that mimic in-vivo dissolution behavior. It was determined that the original marketed product released the initial dose in first half an hour and then the second dose after a period of 5-6 hours. High variability in drug release profiles were observed between various lots. It was decided to investigate the applicability of several new polymers and modern formulation techniques to provide similar but more reproducible release. To reproduce the extended release portion of the tablets, various concentrations of polymer and tabletting excipients were evaluated and an optimum formulation that provided near zero order release was determined. The formulation developed in the laboratory was scaled up to a production size batch. Various physical characteristics of the tablets were evaluated as specified in the USP XXII. Two different types of coating processes, the Accela-cota and fluidized bed coating apparatus (Aeromatic STREA I). were used to coat the tablets with an aqueous polymer latex dispersion to retard drug release from tablet cores for a period of 5-6 hours. These tablets were further coated with 2 mg of albuterol per tablet to provide the immediate ii release dose. Optimum coating parameters were determined for the seal coating and the immediate release coating. A High Performance Liquid Chromatography and UV spectrophotometric assay method were used to determine drug release from the dissolution samples. The USP Apparatus I (Basket) and III (Reciprocating cylinder) dissolution testing methods were used for evaluating drug release from the marketed and the developed products. A statistical evaluation using ANOVA was performed on all the dissolution tests to compare the difference in mean drug release between different batches of the developed product and the marketed product. A significant difference in mean drug release was observed between different lots of tablets at various time points in the marketed product. The in-vitro dissolution data shows that the drug release profile of the developed product is less variable than the marketed product.