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Antibiotics 2019: Effect of drug solubility and accelerated | 45048
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Antibiotics 2019: Effect of drug solubility and accelerated ageing on drug release from polyethylene oxide matrices-Saeed Shojaee-Azad Damgan University

Abstract

Saeed Shojaee, Mehdi Damali Amiry

INTRODUCTION

Hydrophilic matrices are extensively accepted and widely used for oral controlled release (CR) drug delivery systems. Recently, in addition to HPMC, polyethylene oxide (PEO) has been used in the pharmaceutical industry because of its availability in a range of molecular weights, wide regulatory acceptance, and high water-swellability and erosion characteristics (1). As PEO is sensitive to thermal oxidation, it might also be susceptible to free radical oxidative attack. It has been shown that the properties of PEO were subjected to changes because of degradation. The mode, extent and mechanism of degradation are strongly dependent on the intensity and duration of the physical and chemical stresses, to which the polymer is exposed (2). Drug solubility is one of the primary parameters that dictate drug release and dissolution from solid dosage forms. An increase in drug solubility enhanced the diffusion of the drug out of the matrix along with elevated matrix hydration. Moreover, low solubility drugs caused depletion in polymer erosion rates, thus limiting drug release. This is due to insoluble drug particles residing in the gel layer and decreasing the level of swelling and bond formation strength of the polymer chains (3, 4). The aim of this study was to investigate the effect of drug solubility and accelerated ageing (40 °C) on drug release from aged high molecular weight PEO 303 matrices.

Methods

The model drugs (Propranolol HCl, Theophylline and Zonisamide) and PEO 303 were mixed with a 1:1 ratio. Matrix tablets of 240 mg were prepared by the direct compression of the mixture at 1500 psi. The tablets were stored in an oven at 40 °C and at different time intervals (0, 2, 4 and 8 weeks) and the release rate of the tablets were determined using dissolution tester, USP II paddle apparatus. Distilled water at 37 °C was used as a dissolution medium. The drug concentration in the samples was determined by UV spectroscopy at 290, 270 and 271 nm for propranolol, theophylline and zonisamide respectively. A differential scanning calorimetry (DSC) was used to evaluate thermal properties of the polymer.

Results and discussion

The results showed that PEO 303 matrices containing a highly soluble drug (propranolol HCl, 61 mg/ml), had an increased release rate when stored at 40 °C for different period of times (8 > 4 >2 > 0 weeks) (Figure 1a) suggesting that thermo oxidation leads to chain destruction which increased the release rate (2). In case of semi water-soluble drug (theophylline (8 mg/ml)), storage time had no effect on drug release from PEO 303 matrices (Figure 1b). This could be due to solubility of the theophylline which is less than propranolol. Finally, zonisamide was selected as a poorly water soluble drug (0.8 mg/ml) in the present study to cover all the range of solubility.

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