Research Articles
A drug release study from hydroxypropylmethylcellulose (HPMC) matrices using QSPR modeling

https://doi.org/10.1002/jps.20990Get rights and content

ABSTRACT

This investigation is aimed at characterization of the mode of release from two different substitution types of HPMC and the effect of chemical structure of drugs using the QSPR (Quantitative ‐ Structure–Property Relationship) technique. To this end, release profiles of HPMC matrices of several drugs containing the same formulation and compressed at a constant pressure were studied. QSPR method was used to establish statistically significant relationships between release parameters and the structural descriptors. Structural descriptors consisted of molecular mechanical, quantum mechanical and graph‐theoretical parameters, as well as the partition coefficient and the aqueous solubility of the drugs. The results showed that the most important factors determining the release profile from both HPMC K4M and HPMC E4M matrices were the aqueous solubility of drugs (which could be substituted efficiently by dipole moment) and the size of the drug molecules. Comparison of drug release from matrices prepared using the two grades of HPMC showed very distinct differences for some drugs, as evaluated by the similarity factor. The results indicated that the source of the difference could be sought in the drug properties (as exemplified by the aqueous solubility and surface area) as well as the rate of erosion (that depends mainly on the polymer type). © 2007 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 3334–3351, 2007

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INTRODUCTION

A method of obtaining a sustained‐release product is to embed or disperse the solid medicinal compound in an insoluble matrix by compression of a physical mixture of the compound and a polymeric material.1 This has attracted considerable attention and has been described by several researchers.2., 3., 4., 5. Matrix tablets have long been used to obtain sustained drug delivery and it was Higuchi who first presented a detailed mathematical analysis of this release.6

Hyroxypropylmethylcellulose

Materials

Acetaminophen (Acros Organic, UK), diclofenac sodium (Sobhan Co., Iran), fluoxetine HCl (Pars‐Daru, Iran), naproxen (Pars‐Daru, Iran), piroxicam (Sigma, USA), propranolol HCl (Acros Organic, UK), sulfamethoxazole (Logman, Iran), diltiazem HCl (Acros Organic, UK), ibuprofen (Acros Organic, UK), atenolol (Daru‐Pakhsh, Iran), diphenhydramine HCl (Acros Organic, UK), imipramine HCl (Logman, Iran), theophylline monohydrate (Acros Organic, UK), trifluoperazine HCl (Sobhan Co., Iran) and trimethoprim

RESULTS AND DISCUSSION

Various factors could be accounted for the drug release mechanism from hydrophilic matrices.16 These include the geometry of the matrix,17 particle size of polymer and matrix swelling ratio (which depends on the HPMC type and controls water and drug diffusion coefficients),18, 19 polymer and drug concentrations,20, 21 chain length and degree of substitution of the HPMC,19 as well as the drug characteristics.22, 23 An additional factor that might affect the drug release profile is the

CONCLUSION

The process of drug release from HPMC matrices involves the two routes of erosion of the matrix, and diffusion of the dissolved drug through the HPMC gel, each to a varying extent depending on the properties of the drug as well as the polymer grade. QSPR method employed in this investigation was able to outline the major drug properties responsible for the control of release from HPMC matrices. These included drug solubility and the molecular size, with enhancing and reducing effects on the

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