Development of a Directly Compressible Poly(Ethylene Oxide) Matrix for the Sustained-Release of Dihydrocodeine Bitartrate

Abstract

The purpose of this study was to design and evaluate a directly compressible hydrophilic poly(ethylene oxide) (PEO) matrix for the oral sustained delivery of dihydrocodeine bitartrate (DHCT). A direct compression method was used to prepare PEO matrices, and the amount of PEO in the matrices was varied to optimize in vitro DHCT release profiles. In vitro release studies indicated that the matrices containing 20%-70% w/w of PEO with molecular weight of 5.0 x 10(6) showed a similar release profile, as estimated with DT50%, to that exhibited by a marketed product, DHC Continus. In vivo bioavailability study revealed that the difference in the pharmacokinetic parameters such as AUC0-30 and Tmax of the selected sustained-release formulation containing 60% w/w of PEO 5.0 x 10(6) and DHC Continus was statistically insignificant (p > 0.05). Thus, it could be concluded that the extent of bioavailability of the sustained-release formulation developed here was similar to that of DHC Continus although Cmax values of these two preparations were significantly different (p < 0.05). From the data obtained in this research, hydrophilic PEO matrices were found to be a novel sustained-release carrier for the oral delivery of DHCT.

Effect of Drug Solubility on Polymer Hydration and Drug Dissolution from Polyethylene Oxide (PEO) Matrix Tablets

“…This is mainly attributed to the desirable hydration and modified release properties by PEO of variable grades and molecular weights (1)(2)(3)(4). Once in contact with a liquid, PEO will start to hydrate and swell, forming a hydrogel layer that regulates further penetration of the liquid into the matrix and the diffusion of the drug molecules from the dosage form (5).…”

“…Numerous factors from tablet ingredients and preparation can influence drug release from a swellable matrix tablet, which may include drug solubility and drug loading (10)(11)(12), polymer molecular weight and ratio (4,13,14), tablet processing procedure (15), compression force (14,16), and tablet physical configuration (17). Among these parameters drug solubility plays a very important role in modifying the rate and extent of drug release.…”

An Investigation into the Stabilization of Diltiazem HCl Release from Matrices Made from Aged Polyox Powders

“…Polyethylene oxide is a water-soluble non-ionic homo polymer of ethylene oxide, represented by the formula: (OCH 2 CH 2 ) n wherein n represents the average number (ranges from 2 to 180) of oxy-ethylene oxide groups. The use of PEO is mostly attributed to the desirable hydration and modified release properties of the different grades and molecular weights ranging from 100,000 to 7,000,000 (9)(10)(11)(12). PEOs have also been broadly employed for the preparation of sustained released tablets because of ease of production, insensitivity to the pH of the biological medium, high water solubility, high swelling and non-toxicity (8).…”

The Influence of Sodium Carboxymethylcellulose on Drug Release from Polyethylene Oxide Extended Release Matrices

“…Matrices represent a popular and widely used approach for an oral extended release drug delivery due to economic, process development and scale-up reasons (1,2). Polyethylene oxide (3) and sodium carboxymethylcellulose (4) are popular matrix-forming polymers, with wide regulatory acceptance, availability in a range of viscosity grades and good swelling and erosion characteristics, which can be used to modulate the release of various drugs (3)(4)(5)(6)(7)(8)(9)(10)(11).…”