Enhancement of solubility and dissolution rate of ebastine fast-disintegrating tablets by solid dispersion method

Nayyer Islam,Akhtar Rasul,Mohammad Sohail Arshad,Sana Inam,Amjad Hussain,Haroon Khalid Syed,Nasir Abbas,Mohsin Ali,Ikram Ullah Khan,Muhammad Shahid Iqbal,Noor Ul Amin Mohsin,Muhammad Irfan

doi:10.4314/tjpr.v19i9.1

Abstract

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). Keywords: Ebastine, Solid dispersion, Poloxamer 188, Soluplus, Solubility, Dissolution

Highlights

Solubility is a physicochemical feature that relies on a variety of physical and chemical variable of drugs
Methanol was selected as suitable solvent for initial dissolving the drug and further dilutions were made in 0.1 N HCl for preparing standard curve
The absorbance of soluplus, poloxamer, tween 80 and oleic acid was negligible at 252 nm which clearly shows no interference in absorbance of ebastine by these excipients

Summary

Introduction

Solubility is a physicochemical feature that relies on a variety of physical and chemical variable of drugs. Solubility and dissolution rate can be improved by controlling these variables [1]. -©---2-0--2--0---T--h-e---a--u-t-h--o-r-s--.--T-h--i-s--w--o--r-k--i-s--l-i-c-e--n-s--e--d--u--n-d--e--r--th--e---C--r-e-a--t-i-v-e---C--To-r-m-o-mp--o-J-n-P-s-h-A-a-t-rt-rm-i-b-Ru--te-io-s-,n--S-4e-.-p0-t-e-In-m-t-eb--re-nr-a--2t-i0o--2n--0a-;l--L1--i9c-(-e-9n-)-s:--e1--7--9-7 forces in crystal lattice leading to change in solubilization behavior of the drug [2,3]. Solubility has direct relation with dissolution rate and bioavailability of drug molecule [4]. Improved solubility is required to enhance drug absorption and bioavailability [5]. Solid dispersion (SD) is an effective strategy used to increase the solubility of poorly soluble drugs [6]. As ebastine is thermolabile drug, solid dispersion is most suitable system for product development. Such solid dispersions improve the therapeutic efficiency of poorly soluble drugs [7]

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