Selegiline hydrochloride (SL) is chosen as an adjunct for the control of clinical signs of Parkinsonian patients. The aim of the present work is to develop and optimize thermosensitive gels using Pluronic (F-127) for enhancing transport of SL into the brain through the nasal route. SL gels were prepared using a cold method and the Box-Behnken experimental design methodology. Drug (SL), gelling agent (F-127), and emulsifier (Propylene glycol, PG) were selected as independent variables, while the gelation temperature, gel strength, pH, gel content, and gel erosion were considered as dependent variables. For further understanding of the interaction between the various variables, contour plots and surface plots were also applied. Selected formulations, like S10 (contain 25 mg SL, 20 g F-127, and 1 g PG) and S14 (contain 50 mg SL, 18 g F-127 and 1 g PG), had a clear appearance in the sol form, with gelling temperature of the nasal gel ranging between 33 and 34, respectively. The gel strength of the formulations varied from 4.67 and 0.68 mm and the drug content was 100%. The pH of the formulations ranged between 6.71 and 7.11. Detachment force was acceptable (63.69-244.16 N/cm2) to provide prolonged adhesion. In vitro, drug release studies showed that the prepared formulations could release SL for up to 8 h. Permeation flux for the S10 gel was 0.0002 mg/min/cm2. Results demonstrated that the potential use of SL gels can enhance the therapeutic effect of SL through the intranasal administration.
Keywords: Box–Behnken experimental design; F-127; Selegiline hydrochloride; contour plots; nasal; surface plots.