Bio-flexy film formulation for delivery of tiagabine via oro trans-soft palatal route and its in-vitro stability study approach

Abstract

The aim of research work was to formulate bio-flexy films using a novel biopolymer isolated from Rosa polyanthapetals containing tiagabine as a model drug. The soft palate drug delivery helps bypass first-pass metabolism in the liver and pre-systemic elimination in the gastrointestinal tract gets avoided. Tiagabine, anticonvulsant drug possesses t1/2:7-9 hours (low); protein binding: 96%; water solubility: 22mg/L enhances acts as selective GABA reuptake inhibitor. Side effects include abdominal pain, pharyngitis, suicidal thoughts and sudden unexpected death. Rosa polyantha biopolymer used as bio-excipient due to its biodegradability, biocompatibility, non-toxicity, non-reactiveness on soft palatal surface. Physicochemical characterization of biopolymer displayed inbuilt filmability, mucoadhesivity properties. Bio-flexy films were prepared by solvent casting technique. Formulations containing different ratios of nanosized Tiagabine: Rosa polyantha biopolymer (1:0.5, 1:1; 1:3, 1:5, 1:6, 1:10) (FRT1-FRT6) were prepared and compared with nanosized Tiagabine loaded Sodium CMC standard flexy films (FET1-FET6). The percentage yield of Rosa polyantha biopolymer was found to be 2.24±0.01%. Evaluation parameters for formulations revealed Thickness of nanosized Tiagabine loaded bio-flexy films containing Rosa polyantha biopolymer (FRT1-FRT6): 0.027 mm±0.005 to 0.039±0.004 mm, Folding Endurance: 83-130, Surface pH: 7.00±0.04 to 7.00±0.01, Weight Uniformity: 0.008±0.05 to 0.044±0.03, Drug Content Uniformity: 85.6%±0.48 to 94.8%±0.37, Swelling Percentage: 66%±0.2 to 75%±0.1, Percentage Moisture Uptake (PTU): 2.5%±0.14 to 3.8%±0.10. Mucoadhesivity: 90-1440 mins, Mucoretentivity: 110-240 mins. Drug release pattern for formulations FRT1-FRT6 containing Rosa polyantha biopolymer based on the T50% and T80% was found to be FRT5 (1:6) > FRT4 (1:5) > FRT6 (1:10) > FRT1 (1:0.5)> FRT3 (1:3) > FRT2 (1:1). Based on all above mentioned evaluation parameters, FRT5 (containing Tiagabine: Rosa polyantha biopolymer (1:6)) bio-flexy film having R2= 0.9295, Higuchi Matrix as best fit model, follows Fickian Diffusion (Higuchi Matrix) release mechanism, T50%: 7hrs., T80%: 30 hrs. using BITS Software 1.12 was found to be Best formulation.