PEG-based solid dispersions enhanced the solubility and dissolution of eprosartan mesylate in-vitro

Abstract - This study investigates the effect of solid dispersions prepared from of polyethylene glycol (PEG) 3350 and 6000 Da alone or combined with the non-ionic surfactant Tween 80 on the solubility and dissolution rate of a poorly soluble drug eprosartan mesylate (ESM) in attempt to improve its bioavailability following its oral administration.

INTRODUCTION

ESM is a potent anti-hypertension [1]. It has low water solubility and is classified as a Class II drug as per the Biopharmaceutical Classification Systems (BCS) leading to low and variable oral bioavailability (approximately 13%). [2]. Thus, improving ESM solubility and/or dissolution rate would eventually improve the drug bioavailability. Solid dispersion is widely used technique to improve the water solubility of poorly water-soluble drugs employing various biocompatible polymers. In this study, we aimed to enhance the solubility and dissolution of EMS employing solid dispersion (SD) formulated from two grades of poly ethylene glycol (PEG) polymers (i.e. PEG 3350 & PEG 6000 Da) either individually or in combination with Tween 80.

MATERIALS AND METHODS

ESM SDs were prepared by solvent evaporation method using either PEG 3350 or PEG 6000 at various (drug: polymer, w/w) ratios 1:1, 1:2, 1:3, 1:4, 1:5 alone or combined with Tween 80 added at fixed percentage of 0.1 of drug by weight?. Physical mixtures (PMs) of drug and carriers were also prepared at same ratios. Drug solid dispersions and physical mixtures were characterized in terms of drug content, drug dissolution using dissolution apparatus USP II and assayed using HPLC method. Drug dissolution enhancement ratio (ER %) from SD in comparison to the plain drug was calculated. Drug-polymer interactions were evaluated using Differential Scanning Calorimetry (DSC) and FT-IR.

RESULTS AND DISCUSSION

The in vitro solubility and dissolution studies showed SDs prepared using both polymers produced a remarkable improvement (p<0.05) in comparison to the plain drug which reached around 32% (Fig. 1). The dissolution enhancement ratio was polymer type and concentration-dependent. Adding Tween 80 to the SD did not show further dissolution enhancement but reduced the required amount of the polymer to get the same dissolution enhancement. The DSC and FT-IR studies indicated that using SD resulted in transformation of drug from crystalline to amorphous form.

CONCLUSIONS

This study indicated that SDs prepared by using both polymers i.e. PEG 3350 and PEG 6000 improved the in-vitro solubility and dissolution of ESM remarkably which may result in improving the drug bioavailability in vivo.

Acknowledgments

This work is a part of MSc thesis of O.M. Ali at the Faculty of Pharmacy, Aleppo University, Syria.

REFERENCES

[1] Ruilope L, Jager B: Eprosartan for the treatment of hypertension. Expert Opin Pharmacother 2003; 4(1):107-14

[2] Tenero D, Martin D, Wilson B, Jushchyshyn J, Boike S, Lundberg, D, et al. Pharmacokinetics of intravenously and orally administered Eprosartan in healthy males: absolute bioavailability and effect of food. Biopharm Drug Dispos 1998; 19(6): 351- 6.