Nifedipine Molecular Dispersion in Microparticles of Ammonio Methacrylate Copolymer and Ethylcellulose Binary Blends for Controlled Drug Delivery: Effect of Matrix Composition

Abstract

The objective of this study is to explore matrix-type microparticles, comprising a solid dispersion of drug with an ammonio methacrylate copolymer and ethylcellulose binary blend, for use in the controlled release of a poorly water-soluble drug, nifedipine. Microparticles consisting of an ethylcellulose N7 (N7) and Eudragit RL (RL) binary blend at different ratios were prepared using phase-separation methodology. The effects of matrix composition on microparticle properties were evaluated by polarized light microscopy, differential scanning calorimetry (DSC), FT-infrared and UV-visible spectroscopy, stability, and drug release studies. Study results indicate that the particle size distribution, particle morphology, and drug release rate from the microparticles were influenced by the ratio of RL to N7. Discrete spherical microparticles with a narrow size distribution and a controlled release profile were obtained when the ratio of RL to N7 was in the range from 1:1 to 2:1 w/w. Solid-state characterization and release kinetic studies on these microparticles confirmed that the nifedipine release from the microparticles followed the Baker and Lonsdale's matrix diffusion model (1974) for microspheres containing dissolved drug, and the nifedipine diffusion in the microparticle matrix was the rate-limiting step. As the ratio of RL to N7 was changed from 0:1 to 4:1 w/w, the effective drug diffusion coefficient in the micro-matrix increased from 5.8 x 10-10 to 8.6 x 10-9 (cm2/h). In addition, probably due to formation of a stable molecular dispersion promoted by hydrogen bonding between nifedipine and the polymers, no significant changes in the nifedipine physical form or release kinetics were observed after 1-year storage at ambient room temperature followed by 3-month accelerated stability at 40 degrees C/75% RH in a closed container.

pH responsive itaconic acid grafted alginate microspheres for the controlled release of nifedipine

“…Doses of only two to three times the therapeutic dose may cause profound toxicity and side effects in susceptible individuals. Therefore, it is desirable to develop nifedipine controlled-release dosage forms to reduce the side effects, to prevent toxicity, to extend a half-time and to improve patient compliance (Buckley et al, 2007;Huang, Wigent, & Schwartz, 2006). Recently, nifedipine has been used in such controlled-release studies as alginate-methyl cellulose blend microspheres, chitosan-graft-acrylamide microspheres, alginate-chitosan hydrogel beads (Babu et al, 2007;Dai, Li, Zhang, Wang, & Wei, 2008;.…”

Enhancement of the Solubility of Poorly Water Soluble Drugs through Solid Dispersion: A Comprehensive Review

“…Due to which we can administer adequate amount of drug for an extended period of time, which in turn offer many benefits such as reduced dosing frequency leading to patient compliance, decreased side effects, prolonged therapeutic effect for poorly water-soluble and short biological half-life drugs. The polymers which are used include ethyl cellulose, hydroxypropyl cellulose, Eudragit RS, RL, poly (ethylene oxide) and carboxyvinyl polymer [25,26] .…”

Optimization of a novel wax matrix system using aminoalkyl methacrylate copolymer E and ethylcellulose to suppress the bitter taste of acetaminophen

“…EC polymers are widely known to be pH independent and water-insoluble materials. Recent evidence has suggested that the combination of EC and methacrylic polymers at different ratios is able to control drug release (Sanchez-Lafuente et al, 2002;Huang et al, 2006;Feng et al, 2008). Based on these reports, the authors speculated that the incorporation of EC into a wax matrix containing AMCE would control the release of APAP as desired, but little information is available regarding wax matrices composed of a combination of EC and AMCE.…”