Formulation Development and Evaluation of Diphenhydramine Nasal Nano-Emulgel

Abstract

The aim of present study is to formulate diphenhydramine nasal nano-emulgels, having lipophilic nano-sized interior droplets, with better penetration for targeted controlled delivery to mucous membrane. Different diphenhydramine (DPH) nasal nano-emulgels were developed having propylene glycol and olive oil (as permeation enhancers) by using RSM for optimization and then evaluated for physico-chemical characteristics and thermal stability. In-vitro drug release through cellophane membrane was conducted and results were analyzed statistically. Further, gelation, mucoadhesive stress, and ex-vivo and histopathological studies were performed on optimized formulation by using goat nasal membrane. Among all formulations, E2 showed maximum DPH release at higher concentration olive oil (4%) and lower concentration propylene glycol (PG) (25%) within 4 h. All formulations have followed first-order kinetics and drug release mechanism was Fickian diffusion. Analysis of variance (ANOVA) and multiple linear regression analysis (MLRA) were used to compare results among formulations and 3D surface plots were constructed also. Optimized formulation showed immediate prolong gelation in artificial nasal mucosa and excellent mucoadhesive property (72.5 ± 1.5 dynes/cm). Approximately 97.1% optimized formulation was permeated through membrane within 4 h, having a high flux rate (33.19 ± 0.897 μg/cm/min) with diffusion coefficient (0.000786 ± 4.56 × 10 cm/min) while drug contents remained on mucosal membrane for 24 h. Histopathologically, change on intra-mucosal surface of excised membrane was observed due to passage of drug through it. In summary, combination of PG and olive oil in nasal DPH nano-emulgel can be utilized successfully for targeted controlled delivery. The optimized formulation has excellent permeability and prolonged residence time on mucosal surface, which prove its good anti-histaminic activity in case of allergic rhinitis.

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“…For this, three volunteers were selected, and a small amount of optimized CPM gel (FM6) was applied on an area of 2 square inches to the back of the hand. The volunteers were observed for lesions or irritation, and no irritation was reported by the volunteers, which confirmed the suitability of the gels 17 .…”

“…All other chemicals used in this study were of analytical grade and were used without further purification. Experimental Design: A central composite design (CCD) with α = 2 was employed to prepare the gels as described previously 17,19 . The factors, namely PG (X1) and PEG (X2) planned at 5 levels were selected based on the results of preliminary experiments.…”

“…The extent of absorption will then be dependent on the physicochemical properties of the penetrant and the vehicle. In addition to that, easiness of application and whether the patients accept the product contribute substantially toward the success of topical formulations 12,13 . For example, products which are unpleasant to touch are unlikely to be accepted by the patients regardless of its potential benefits 14 .…”

“…Gels are semisolid preparations with excellent acceptability in cosmetic, pharmaceutical and food technologies 15 . The gels are typically formed from a liquid phase that has been thickened with a minor component that usually is a gelling agent 16,17 . The continuous liquid phase allows free diffusion of molecules through the three-dimensional polymeric scaffolds of the gels, and hence drug release should be equivalent to that from a simple solution.…”

“…Then benzyl alcohol and ethylene glycol were added in it with continuous stirring. The mixture was neutralized using triethanolamine, and the final volume up to 100 g of gel was adjusted with the help of double distilled water 17 . 20 .…”