Study of Verapamil hydrochloride release from compressed hydrophilic Polyox-Wsr tablets

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Abstract

This study deals with Verapamil hydrochloride release from tablets based on high molecular weight poly(ethylene oxide) (PEO). The drug release proceeds as a controlled diffusion (n=0.44–0.47), which rate is dependent on the molecular weight of PEO. Independent from it, under the conditions of the Half-change test, the drug release practically ceases after 4 h as a result of obtaining low soluble in the water base. The introduction of hydrophilic polymers with pH dependent solubility (Eudragit L, Eudispert hv and Carbopol 934) at concentrations of 10÷50% with respect to PEO amount keeping constant the ratio drug: matrix insures relatively complete release both in alkali medium and under the conditions of the Half-change test. Meanwhile drug release kinetics also changes — the release of all models studied runs as a typical abnormal diffusion (a=0.66–0.87), i.e. like a diffusion-relaxation controlled process. The decrease in drug concentration leads not only to retarded release of the drug sample but also to changes in the kinetics of the process. At lower drug concentrations on the matrix from a typical abnormal diffusion it turns into a relaxation controlled diffusion (n10%=1).

Introduction

Nowadays polymers with their unique properties (harmlessness and availability) have been widely applied in the development of drug delivery systems. (Dittgen et al., 1997). Hydrophilic polymers like hydroxy propyl methyl cellulose (HPC), polyvinyl alcohol (PVA), as well as acrylacid derivatives, PHEMA (hydroxyethylmethyl acrylate) methyl methacrylate, vinyl acetate, ethylene oxide, etc., have been already used for preparation of oral drug release systems (Zhang et al., 1990). Recently, it has been established that noncrosslinked low molecular weight poly(ethylene oxide) (PEO) (Mw=0.6×106) insures constant release rate by means of forming a homogeneous gel of even thickness. When the drug is loaded onto model matrices, based on PEO of higher molecular weight (4×106 and higher), the release is controlled by the swelling of the polymer, not by its erosion. This leads to the inconstant rate of release, inducing by the diffusion of the drug through the swollen gel layer (Kim, 1995). Being harmless and stable makes PEO a suitable carrier for drug delivery systems. Its good compressibility allows the preparation of hydrogel matrices by direct compression.

This paper presents the study on the release of Verapamil hydrochloride. Which characterizing with pH dependent water solubility, loaded onto hydrogel matrices based on high molecular weight PEO. The aim of the investigation was to clarify the possibility of improving the drug release. The effect of PEO molecular weight and the concentration of the drug loaded onto the matrix, are major factors determining the drug release from hydrogels, they been investigated as well as the possibility for increasing the PEO matrix permeation, by addition of polymeric supplements, with a view to insure a uniform and complete drug release.

Section snippets

Materials

Polyox-Wsr NFs of average molecular weight from 0.9×106 to 8×106 were supplied by Union carbide corp., USA. Verapamil hydrochloride was purchased from Pharmachim, AG, Sofia, Bulgaria. Carbopol 934 was purchased from Hercules and Eudragit L and Eudispert hv were purchased from Rohm pharma G.m.b.H. Germany. The materials were used as received.

Preparation of tablets

The ingredients (PEO, drug, magnesium stearate and Eudragit L or Eudispert hv or Carbopol 934) were mixed and then tableted using a single punch tablet

Investigations, results, and discussion

Matrix tablets were prepared from Polyox-Wsr of various molecular weights (0.9×106, 2×106, 4×106, 7×106, and 8×106 Da) by direct compression. The release of the model compound was studied under the conditions of the Half-change test. Summary results from in vitro drug release experiments, are shown in Fig. 1. As seen the molecular weight of the polymer affects significantly the drug release — the higher the molecular weight, the smaller the amount of the drug released. While more than 50% of

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