MODULATORY EFFECT OF POLYMER TYPE AND CONCENTRATION ON DRUG RELEASE FROM SUSTAINED RELEASE MATRIX TABLETS OF RANOLAZINE: A COMPARATIVE RELEASE KINETIC STUDY

  • AHMED M AGIBA Department of Formulation, R&D Directorate, October Pharma, 6th of October City, Giza, Egypt. https://orcid.org/0000-0003-3635-9093
  • WAGEEH ABDEL HAKEEM Department of Methodology and Stability, R&D Directorate, October Pharma, 6th of October City, Giza, Egypt.
  • ASHRAF G ZAYED Department of Methodology and Stability, R&D Directorate, October Pharma, 6th of October City, Giza, Egypt.

Abstract

Objective: Ranolazine (RZ), antianginal drug indicated for the treatment of chronic stable angina pectoris, was formulated into sustained-release matrix tablets and optimized to improve patient compliance and achieve controlled release over a certain period.


Methods: Different formulations were prepared by wet- and melt-granulation techniques. Excipients at different ratios as Eudragit® L100-55, Methocel™ E5, Avicel® PH-101, and carnauba wax powder were used to develop a ternary polymeric matrix system for the controlled delivery of RZ. The prepared formulations were subjected to granulometric and characteristic studies. Comparative dissolution and release kinetic studies of the selected formulation and the reference product, Ranexa® extended-release film-coated tablets, Gilead Sciences, Inc., USA, were further carried out to ensure product similarity.


Results: The optimum pH-dependent to pH-independent polymers ratio was 1:1.3 (w/w). Extragranular carnauba wax in a concentration of 32.50 mg/tablet (2.50 gm% w/w) was the key excipient in controlling drug release kinetics by forming waxy matrix granules which prevent rapid dissolution. Modulation of the microenvironmental pH using a potent alkalinizing agent was very effective for controlling drug release patterns in different dissolution media from pH 1.2–6.8.


Conclusion: The release of RZ from the matrix tablets was controlled for a period of 24 h, and thereby expected to provide patient compliance with minimal side effects.

Keywords: Sustained release, Ranolazine, pH-independent polymer, pH-dependent polymer, Film-former carnauba wax, Microenvironmental pH modulation, Wet-granulation, Melt-granulation

Author Biography

AHMED M AGIBA, Department of Formulation, R&D Directorate, October Pharma, 6th of October City, Giza, Egypt.

Agiba, A.M. has a bachelor's degree in pharmaceutical sciences and industrial pharmacy from Misr University for Science and Technology (Egypt) with a general grade of Excellent First-Class Honors, a master of pharmaceutical sciences with a specialization in pharmaceutics from Ain Shams University (Egypt), and a master of science in biotechnology from University of Chemical Technology and Metallurgy (Bulgaria) and University of Oviedo (Spain) with a general grade of Excellent (Erasmus Mundus Scholarship).

Agiba, A.M. was granted two research fellowships: Joint NAM S&T Centre – ICCBS Research Fellowship at ICCBS, University of Karachi (Pakistan) and FCT Research Grant at CICECO – Aveiro Institute of Materials (Portugal), plus an internship at Bajcsy-Zsilinszky Kórház és Rendelőintézet (Hungary).

Agiba, A.M has worked for top leading pharmaceutical industries in the Middle East, Africa, and worldwide: SIGMA Pharmaceutical Industries as a product development senior specialist at Formulation R&D, Egyptian Armed Forces Pharmaceutical Factory as a principal researcher, Pharco-B International, a member of Pharco Corporation, as a R&D section head at Formulation R&D, and October Pharma as R&D section head at Formulation R&D.  

Agiba, A.M has 6 international research/review articles in high-quality, peer-review journals, 8 international conference papers and 2 theses.

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M AGIBA, A., W. A. HAKEEM, and A. G ZAYED. “MODULATORY EFFECT OF POLYMER TYPE AND CONCENTRATION ON DRUG RELEASE FROM SUSTAINED RELEASE MATRIX TABLETS OF RANOLAZINE: A COMPARATIVE RELEASE KINETIC STUDY”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 13, no. 9, July 2020, pp. 132-40, doi:10.22159/ajpcr.2020.v13i9.38500.
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