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Orodispersible sublingual films (OSFs) composed of hydrophilic polymers were loaded with poloxamer-188 and d-α-tocopheryl polyethylene glycol succinate (TPGS-1000) mixed micelles to improve the oral bioavailability of a poorly soluble drug, ebastine (EBT). Mixed micelles formed by thin-film hydration method were incorporated into orodispersible sublingual film, consisting of HPMC and glycerol, using solvent casting technique. The mixed micelles and films were thoroughly evaluated for physicochemical characterization (size, polydispersity index, zeta potential, entrapment efficiency, thickness, weight, surface pH studies, disintegration time, swelling indices, mechanical properties, FTIR, PXRD, DSC, SEM, AFM, in vitro drug release, in vivo bioavailability, and toxicological studies). The results showed that the average particle size of mixed micelles was 73 nm. The mean zeta potential and PDI of the optimal mixed micelles formulation were −26 mV and 0.16, respectively. Furthermore, the maximum entrapment efficiency 82% was attained. The film's disintegration time was in the range of 28 to 102 s in aqueous media. The integrity of micelles was not affected upon incorporation in films. Importantly, the micelles-loaded films revealed rapid absorption, high permeability, and increased bioavailability of EBT as compared to the pure drug. The existence of ebastine loaded mixed micelles in the films enhanced the bioavailability about 2.18 folds as compared to pure drug. Further, the results evidently established in-vitro and in-vivo performance of bioavailability enhancement, biocompatibility, and good safety profile of micelles-loaded orodispersible EBT films. Finally, it was concluded that film loaded with poloxamer-188/TPGS-1000 mixed micelles could be an effective carrier system for enhancing the bioavailability of ebastine. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficiency of different solubilizing agents in improving solubility as well as dissolution rate of ebastine (a BCS class II drug) by incorporating prepared solid dispersion into fast disintegrating tablets. Method: The solubility of ebastine was determined in distilled water, lipids and solubilizing agents. Subsequently, the binary solid dispersions were prepared by kneading method using varying weight ratios of ebastine and solubilizing agents. The solid dispersions were then incorporated into fast disintegrating tablets (SD-FDT). Central composite rotatable design (CCD) was used to determine the impact of super disintegrating agents on disintegration time and friability of tablets. The solubility and dissolution rate of developed SD-FDT were compared with a marketed brand. The solid dispersion particles were characterized by Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder x-ray diffraction (P-XRD) and scanning electron microscopy (SEM). Results: The saturated solubility of pure ebastine in water was 0.002 ± 0.041 mg/ml while the aqueous solubility of EBT/poloxamer solid dispersion SET3 (P) was 0.018 ± 2.510 mg/ml; on the other hand, EBT/soluplus solid dispersion SET1(S) has an aqueous solubility of 0.242 ± 1.390 mg/ml. Within 30 min, drug release was 14.00 ± 1.77, 78.00 ± 2.31 and 98.70 ± 2.54% from pure EBT, SET3 (P) and SET1(S), respectively. Conclusion: The solubility and dissolution rate of ebastine has been successfully enhanced by incorporating its solid dispersion in fast-disintegrating tablets (SD-FDT). [ABSTRACT FROM AUTHOR]