OPTIMIZATION OF COMPONENT VARIABLES BY STATISTICAL APPROACH FOR DESIGN OF CHRONOTHERAPEUTIC DOSAGE FORM FOR HYPERTENSION
Objective: Blood pressure (BP) pursues circadian rhythms projecting its highest values during early morning and lowest during night. The aim of the present investigation was to design a newer programmable chronotherapy based capsule system containing delayed release microspheres of losartan potassium for effective management of hypertension.
Methods: First, the microspheres were prepared with Eudragit RS100 by optimization technique through the application of Design Expert® software. The optimized microsphere formulation was filled in a capsule shell, and these shells were coated with 10% w/v Eudragit L100:Eudragit S100 (in ratio 1:2), in isopropyl alcohol: water as solvent system, to provide the necessary delay in emptying of capsule content. The whole capsular system was evaluated by various characteristic formulation parameters. Validation of optimization model and statistical interpretation of results was done using analysis of variance.
Results: The results indicated that the optimized triple coated capsule shells showed an extended release of drug from microspheres after a lag time of 4 h.
Conclusion: Conclusively, the chronotherapeutic system of losartan potassium was successfully developed to be dosed at bedtime that could benefit from the known circadian rhythms of the disease to control the BP for once a day therapy
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