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; WAGEEH ABDEL HAKEEM; ASHRAF G ZAYED

doi:10.22159/ajpcr.2020.v13i9.38500

Authors

AHMED M AGIBA Department of Formulation, R and 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 and D Directorate, October Pharma, 6th of October City, Giza, Egypt.
ASHRAF G ZAYED Department of Methodology and Stability, R and D Directorate, October Pharma, 6th of October City, Giza, Egypt.

DOI:

https://doi.org/10.22159/ajpcr.2020.v13i9.38500

Keywords:

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

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.

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Author Biography

AHMED M AGIBA, Department of Formulation, R and 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.

References

Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F, et al. Guidelines on the management of stable angina pectoris: Executive summary: The task force on the management of stable angina pectoris of the European society of cardiology. Eur Heart J 2006;27:1341-81.

Vitulano N, Cialdella P, Gustapane M, Vitulano L, Pedicino D, Pelargonio D. Ranolazine: Beyond the treatment of chronic stable angina pectoris. Int J Clin Cardiol 2015;2:1-6.

Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A, et al. 2013 ESC guidelines on the management of stable coronary artery disease: The task force on the management of stable coronary artery disease of the European society of cardiology. Eur Heart J 2013;34:2949-3003.

Holubkov R, Laskey WK, Haviland A, Slater JC, Bourassa MG, Vlachos HA, et al. Angina 1 year after percutaneous coronary intervention: A report from the NHLBI dynamic registry. Am Heart J 2002;144:826-33.

Hueb W, Soares PR, Gersh BJ, César LA, Luz PL, Puig LB, et al. The medicine, angioplasty, or surgery study (MASS-II): A randomized, controlled clinical trial of three therapeutic strategies for multivessel coronary artery disease: One-year results. J Am Coll Cardiol 2004;43:1743-51.

Nash DT, Nash SD. Ranolazine for chronic stable angina. Lancet 2008;372:1335-41.

Reddy BM, Weintraub HS, Schwartzbard AZ. Ranolazine: A new approach to treating an old problem. Tex Heart Inst J 2010;37:641-7.

Ranexa (Ranolazine) Extended-Release Tablets, for Oral Use. Gilead Sciences; 2019. Available from: https://www.gilead.com/~/media/files/ pdfs/medicines/cardiovascular/ranexa/ranexa_pi.pdf. [Last accessed on 2020 Apr 25].

Jerling M. Clinical pharmacokinetics of ranolazine. Clin Pharmacokinet 2006;45:469-91.

Jerling M, Abdallah H. Effect of renal impairment on multiple-dose pharmacokinetics of extended-release ranolazine. Clin Pharmacol Ther 2005;78:288-97.

Jerling M, Huan BL, Leung K, Chu N, Abdallah H, Hussein Z. Studies to investigate the pharmacokinetic interactions between ranolazine and ketoconazole, diltiazem, or simvastatin during combined administration in healthy subjects. J Clin Pharmacol 2005;45:422-33.

Antonopoulos MS, Lee J, Chang A. Ranolazine (Ranexa): A first-in-class therapy for stable angina. P T 2007;32:488-93.

Chen X, Wen H, Park K. Challenges and new technologies of oral controlled release. In: Oral Controlled Release Formulation Design and Drug Delivery: Theory to Practice. New York: John Wiley & Sons Inc.; 2010. p. 257-77.

Zalte HD, Saudagar RB. Review on sustained release matrix tablet. Int J Pharm Biol Sci 2013;3:17-29.

Tapaswi RD, Verma P. Matrix tablets: An approach towards oral extended release drug delivery. Int J Pharm Res Rev 2013;2:12-24.

Asaduzzaman M, Rahman MR, Khan MS, Islam SA. Development of sustain release matrix tablet of ranolazine based on methocel K4M CR: In vitro drug release and kinetic approach. J Appl Pharm Sci 2011;1:131-6.

Uddin MN, Ahmed I, Roni MA, Islam MR, Rahman MH, Jalil RU. In vitro release kinetics study of ranolazine from swellable hydrophilic matrix tablets. Dhaka Univ J Pharm Sci 2009;8:31-8.

Rahman MM, Hasan SM, Alam A, Roy S, Jha MK, Ahsan MQ, et al.Formulation and evaluation of ranolazine sustained release matrix tablets using Eudragit and HPMC. Int J Res Pharm Biomed Sci 2011;1:172-7.

European Pharmacopoeia. The Directorate for the Quality of Medicines of the Council of Europe 9EDQM. Strasbourg, France: European Pharmacopoeia; 2002.

Priya RM, Natarajan R, Rajendran NN. Design and in vitro evaluation of sustained release tablets of ranolazine. Int J Pharm Sci Res 2011;2:922-8.

Moore JW, Flanner HH. Mathematical comparison of curves with an emphasis on in-vitro dissolution profiles. Pharm Tech 1996;20:64-74.

Wagner JG. Interpretation of percent dissolved-time plots derived from in vitro testing of conventional tablets and capsules. J Pharm Sci 1969;58:1253-7.

Higuchi T. Rate of release of medicaments from ointment bases containing drugs in suspension. J Pharm Sci 1961;50:847-75.

Hixon AW, Crowell JH. Dependence of reaction velocity upon surface and agitation. Ind Eng Chem 1931;23:923-31.

Korsmeyer RW, Gurny R, Doelker EM, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 1983;15:25-35.

Khan KA. The concept of dissolution efficiency. J Pharm Pharmacol 1975;27:48-9.

Podczeck F. Comparison of in vitro dissolution profiles by calculating mean dissolution time (MDT) or mean residence time (MRT). Int J Pharm 1993;97:93-100.

Lucas TI, Bishara RH, Seevers RH. A stability program for the distribution of drug products. Pharm Tech 2004;28:68-73.

Agiba AM, Abdel-Hamid S, Nasr M, Geneidi AS. Geriatric-oriented high dose nutraceutical ODTs: Formulation and physicomechanical characterization. Curr Drug Deliv 2018;15:267-77.

Agiba AM, Eldin AB. Insights into formulation technologies and novel strategies for the design of orally disintegrating dosage forms: A comprehensive industrial review. Int J Pharm Pharm Sci 2019;11:8-20.

Badawy SI, Hussain MA. Microenvironmental pH modulation in solid dosage forms. J Pharm Sci 2007;96:948-59.

Tran PH, Tran TT, Lee KH, Kim DJ, Lee BJ. Dissolution-modulating mechanism of pH modifiers in solid dispersion containing weakly acidic or basic drugs with poor water solubility. Expert Opin Drug Deliv 2010;7:647-61.

Tran TT, Tran PH, Choi HG, Han HK, Lee BJ. The roles of acidifiers in solid dispersions and physical mixtures. Int J Pharm 2010;384:60-6.

Noyes AA, Whitney WR. The rate of solution of solid substances in their own solutions. J Am Chem Soc 1897;19:930-4.

Siepe S, Lueckel B, Kramer A, Ries A, Gurny R. Assessment of tailor-made HPMC-based matrix minitablets comprising a weakly basic drug compound. Drug Dev Ind Pharm 2008;34:46-52.

Siepe S, Lueckel B, Kramer A, Ries A, Gurny R. Strategies for the design of hydrophilic matrix tablets with controlled microenvironmental pH. Int J Pharm 2006;316:14-20.

Ploen J, Andersch J, Heschel M, Leopold CS. Citric acid as a pH-modifying additive in an extended release pellet formulation containing a weakly basic drug. Drug Dev Ind Pharm 2009;35:1210-8.

Rowe RC, Sheskey PJ, Owen SC. Handbook of Pharmaceutical Excipients. 6th ed. Washington, DC: American Pharmacists Association; 2009.

Mitchell K, Ford JL, Armstrong DJ, Elliott PN, Rostron C, Hogan JE. The influence of additives on the cloud point, disintegration and dissolution of hydroxypropylmethylcellulose gels and matrix tablets. Int J Pharm 1990;66:233-42.

Rajabi-Siahboomi AR, Bowtell RW, Mansfield P, Davies MC, Melia CD. Structure and behavior in hydrophilic matrix sustained release dosage forms: 4. Studies of water mobility and diffusion coefficients in the gel layer of HPMC tablets using NMR imaging. Pharm Res 1996;13:376-80.

Karna S, Chaturvedi S, Agrawal V, Alim M. Formulation approaches for sustained release dosage forms: A review. Asian J Pharm Clin Res 2015;8:34-41.

Anderson NH, Bauer M, Boussac N, Khan-Malek R, Munden P, Sardaro M. An evaluation of fit factors and dissolution efficiency for the comparison of in vitro dissolution profiles. J Pharm Biomed Anal 1998;17:811-22.