Formulation and Evaluation of Mucoadhesive Nasal Microspheres of Hydralazine Hydrochloride
Purpose: Nasal delivery protects drugs like Hydralazine Hydrochloride from hepatic first-pass metabolism. The study aimed to formulate mucoadhesive sodium alginate and Carbopol 934P microspheres loaded with Hydralazine Hydrochloride. Methods: Microspheres were prepared by emulsion crosslinking method, with mucoadhesive polymers (Sodium alginate-carbopol-934P), for potential nasal delivery bypassing first-pass metabolism. Relevant physicochemical properties, in vitro release and Mucoadhesion, drug content and Particle size analysis were investigated. Microspheres were spherical in shape, distinct, with smooth properties favorable for intranasal absorption. Results: Kinetic modeling result suggested that the prepared formulation followed the korsemeyer-Peppas. Pronounced sustained drug release over 8 hours was exhibited upon incorporation of Carbopol 934P and Sodium alginate. An invitro mucoadhesive test showed that Hydralazine Hydrochloride mucoadhesive microspheres adhered more strongly to the mucous layer and retained in the gastrointestinal tract for an extended period of time. A 32 full factorial design was employed to study the effect of independent variables, drug-to-polymer-to-polymer ratio (Hydralazine Hydrochloride –Sodium alginate-carbopol-934P) (X1), and stirring speed (X2) on dependent variables, i.e. percentage of mucoadhesion, drug entrapment efficiency, particle size and t80. The best batch exhibited a high drug entrapment efficiency of 53.94 %; 81% mucoadhesion after 1 h and particle size of 120 μm. A sustained pattern of drug release was obtained for more than 12 h. The drug-topolymer-to-polymer ratio had a more significant effect on the dependent variables. Conclusion: The prolonged gastrointestinal residence time and slow release of Hydralazine Hydrochloride resulting from the mucoadhesive microspheres, could contribute to the provision of a sustained anti-hypertensive effect.
