Formulation Development and Evaluation of Nasal Mucoadhesive Dosage form containing Desmopressin acetate: An in vivo Ex vivo characterization

Abstract

Nocturnal enuresis (bed wetting) is an involuntary loss of urine at night in children. newlineCentral diabetes insipidus (CDI) occurs in a wide age range of people and typical newlinesymptoms of CDI are presence of resistant excessive urination (polyuria) which is newlinefollowed by excessive thirst (polydipsia). The treatment of choice in nocturnal enuresis newlineand CDI is desmopressin and is available as parenteral, intranasal and tablet forms. It has newlinea low oral bioavailability and dislike of injection the alternative is intranasal route, but newlinelower retention time of solution in nasal cavity resulting in poor bioavailability and less newlinetransfer of drug directly to the brain through the olfactory pathway. To the best of our newlineknowledge, no information is available in the literature on the improvement of newlineDesmopressin bioavailability by formulating dry nasal powder (DNP) and newlinethermoreversible in situ gel using mucoadhesive polymer. The present research was newlineaimed to explore dry nasal powder by spray drying method and thermoreversible in situ newlinegel formulation development using 32 factorial design to enhance drug residence time at newlineits absorption site, improve the stability of peptide hormone due to its dry form and newlineincrease the bioavailability of desmopressin acetate. Dry nasal powder were prepared by newlinespray drying method using different mucoadhesive polymer like HPMC (Methocel E5), newlinecarbopol 934P and chitosan and on the basis of preliminary trials formulation was newlineoptimized using 32 factorial design. The 32 factorial design was employed using polymer newlineconcentration and feed rate as independent variables and particle size and % yield were newlinetaken as dependent variables. The optimized batch was selected using Design Expert newlinesoftware employing overlay plot with desirability approach. The dry nasal powder newlineformulations were evaluated for particle size, mucoadhesive strength, % yield, % drug newlinecontent, scanning electron microscopy, DSC study, nasal toxicity study, ex vivo drug newlinerelease study, stability study and in vivo study. The composition of optimized newlineformulat