Design and development of intranasal in situ gelling system of Midazolam hydrochloride using 32 full factorial design

The aim of the present study was to develop and optimize ion sensitive in situ gel for the intranasal delivery of Midazolam hydrochloride using 32 full factorial design. The in situ nasal gel was prepared using gellan gum as an ion activated in situ gel forming polymer and carbopol 934P as a mucoadhesive agent. The effect of two independent factors concentration of gellan gum (X1) and concentration of carbopol 934P (X2) on viscosity at non physiological condition (Y1), viscosity at physiological condition (Y2), mucoadhesive strength (Y3), % cumulative drug release in 10 min (Y4)and in 180 min (Y5) were studied. The data were statistically analyzed using ANOVA and a p < 0.05 was considered statistically significant. Three dimensional surface response plots were drawn to evaluate the interaction of independent variables on the chosen responses. The permeability through goat nasal mucosa was 85.139 ± 5.87% in 180 min, steady state flux and permeability coefficient were 36.559 μm cm−2hr−1 and 7.3118 × 10−3 cmhr−1 respectively, which showed good permeability of drug. In situ nasal gel was found to be non-toxic to biological membrane in histopathological evaluation.

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