Development and Evaluation of Novel Formulation of Mirabegron

Abstract

Overactive bladder (OAB) is a chronic urinary storage disorder marked by sudden involuntary contraction of urinary bladder with unnatural urinary urgency irrespective of incontinence. Antimuscarinic drugs are US Food and Drug administration approved medications for OAB. Recently, novel findings in pathophysiology of OAB indicates potential role of and#946;3-adrenoceptor (AR) agonists. In this class mirabegron (YM178) is a novel, once-daily orally active, first-in-class, potent and#946;3-AR agonist. The only available marketed formulation is developed using a stable crystalline polymorph of the API. The marketed formulation is well protected by family of patents till 2023. Being the only class of drug available for increasing number of patients worldwide it was a need of the day to develop a novel technique followed by an extended-release dosage form of Mirabegron. Amorphous form of mirabegron offers solution to such problem but poor chemical stability is a major challenge. Thus, chemical stabilization of amorphous mirabegron complex followed by development of extended-release formulation to maintain therapeutic concentration for longer duration would be an advantageous approach for effective management of OAB. The application of cyclodextrin is prominently used for the solid-state transformation and enhancement in solubility and stability of active. newlineIn the present study Stable amorphous mirabegron complex was developed with improved solubility, stability, and extended release action. HPand#946;CD was screened as a suitable complexing agent, the addition of butylated hydroxytoluene and ethyl cellulose improved chemical stability and extended the release of the. XRPD diffractogram of mirabegron complex demonstrated the preservation of amorphous form. ATR-FTIR spectra of mirabegron and complex demonstrated significant changes in functional groups before and after complex formation. 23 Full factorial design was used to optimize the mirabegron complex. Stastically optimized mirabegron complex showed 81.4 ± 2.8% release at 12 h.