Development and Evaluation of Mucoadhesive Bio-Flexy Films Using a Novel Biopolymer from Solanum melongena Loaded with Nanosized Topiramate

Abstract

Purpose: To purpose of this research work was to develop nanosized Topiramate loaded bio-flexy films containing biopolymer isolated from natural edible source of Solanum melongena pulp. Soft palate drug delivery bypasses first-pass metabolism in gastrointestinal tract. The biopolymer was isolated from pulp of Solanum melongena as bio-excipient cum retardant for preparing bio-flexy films due to its biodegradable, biocompatible, non-toxic nature, inertness to soft palatal mucosal surface. Topiramate, anticonvulsant drug which is used for treatment of Epilepsy by reducing glutamatergic neurotransmission have adverse effects like stomach pain, inflammation of pharynx, suicidal ideation and sudden unexpected death in epilepsy (SUDEP). Thus, the adverse reactions are minimized by reducing dose, dose frequency which can be achieved by nanosizing of drug and its smart delivery by Soft Palatal route. Method: Topiramate was nanosized using Solvent Evaporation and Sonication methods respectively. Nanosized Topiramate loaded bio-flexy films containing isolated Solanum melongena biopolymer were prepared by Film Solvent Casting Technique. Formulations containing different ratios of Topiramate: Solanum melongena biopolymer (1:1; 1:3, 1:5, 1:6, 1:10) (FMO1-FMO5) were taken in mortar. Optimized quantity of Dextrose, Fructose and Glycerin were added and triturated properly. Added Distilled Water up to 20 mL uniformly triturated for 2 mins. Mixtures were subjected to Magnetic Stirring for 45 mins, followed by sonication for 5 cycles (each cycle 180 seconds). 10 mL of the solutions were poured into petridishes. Kept for natural drying for 24 hours. Removed by rinsing with 0.1 mL of 1% borax solution. Checked filmability of prepared films. Evaluation parameters were performed for Mucoretentivity, Swelling Index, Thickness, Tensile Strength, Folding Endurance, Surface pH, Weight Uniformity, Drug Content Uniformity, Percentage Moisture Uptake (PTU), in vitro release, and stability studies. Results: The isolated Solanum melongena biopolymer showed percentage yield of 0.58% ± 0.02. Significant mucoretention of prepared bio-flexy films was observed on Capra aegagrus intestinal mucosa in comparison with standard Sodium Carboxyl Methyl Cellulose films. Swelling Percentage of nanosized Topiramate loaded bioflexy films containing Solanum melongena biopolymer (FMO1-FMO5) was ranging from: 70% ± 0.5 to 73% ± 0.3, Thickness 0.027 ± 0.006 mm to 0.037 ± 0.002 mm, Tensile Strength: 89.38 g ± 2.8 to 100.05 g ± 2.4, Folding Endurance: 102-167, Surface pH: 7.01 ± 0.05 to 7.01 ± 0.03, Weight Uniformity: 0.020 ± 0.05 to 0.031 ± 0.04, Drug Content Uniformity: 90.4% ± 0.65 to 98.6% ± 0.60, Percentage Moisture Uptake (PTU): 2.2% ± 0.13 to 2.6% ± 0.12. Conclusion: The bio-flexy film FMO1 prepared using Topiramate: Solanum melongena biopolymer in ratio of 1:1 was taken as Best film. It showed Regression square value of 0.9618, Higuchi Matrix equation as best fit model, followed Anomalous Transport release mode of action, Time required for 50%, drug release was 24 hours and for 80% drug release was 32 hours as per BITS Software. Stability study showed stable bio-flexy films. Prepared formulations of Topiramate loaded bio-flexy films containing Solanum melongena biopolymer were appropriate for Soft Palatal Delivery as it showed significant mucoretention due to its bio-polymeric nature.