PHARMACOKINETIC STUDY IN HUMANS AND IN VITRO EVALUATION OF BIOENHANCED BILAYER SUBLINGUAL FILMS FOR THE MANAGEMENT OF ACUTE MIGRAINE

Abstract

Objective: Long-lasting migraine pain is one of the most disabling neurological disorders and requires a quick onset of action from the administered dosage form. This study aimed to provide sublingual administration of the frequently used combination of NSAID and triptan in order to trigger their action immediately by escaping the first-pass metabolism, simultaneously improving patient compliance. Methods: In the present research, sublingual bilayer films were developed by joining the two loaded layers with zolmitriptan and piroxicam, respectively. Each layer was prepared and loaded separately using the traditional solvent casting method. Mechanical support was provided by the 1:1 combination of HPMC E-15 and pullulan, which were used as water-soluble film-forming polymers with polyethylene glycol 400 as a plasticizer. Films were evaluated for various physicochemical and mechanical properties. Finally, a pharmacokinetic study was performed on six healthy human volunteers to compare the PK parameters of the best formulation, BSTF-3, with those of a commercially available formulation. Sepitrap 80 and Sepitrap 4000 were used as bio-enhancers to achieve faster systemic delivery. Results: The thin, flexible bilayer films were observed to provide quick action alone with increase patient compliance by preventing the first-pass metabolism and dysphagia. Sepitrap 80 successfully increased the permeation of both drugs. Approximately 92 percent of zolmitriptan was released from the formed bilayer sublingual thin films within 3 min, whereas 92 percent of piroxicam was released within 4.5 min from the best formulation. Within 30 min of the commencement of the pharmacokinetic investigation, plasma concentrations of the active component began to rise rapidly. Conclusion: When compared to commercial formulations, the developed films had a greater AUC and Cmax with a shorter Tmax, indicating a faster trigger of action and higher bioavailability.