PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
 
AAPS PharmSciTech. 2003 December; 4(4): 480–488.
Published online 2003 October 20. doi:  10.1208/pt040461
PMCID: PMC2750654

Once-daily sustained-release matrix tablets of nicorandil: Formulation and in vitro evaluation

Abstract

The objective of the present study was to develop once-daily sustained-release matrix tablets of nicorandil, a novel potassium channel opener used in cardiovascular diseases. The tablets were prepared by the wet granulation method. Ethanolic solutions of ethylcellulose (EC), Eudragit RL-100, Eudragit RS-100, and polyvinylpyrrolidone were used as granulating agents along with hydrophilic matrix materials like hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose, and sodium alginate. The granules were evaluated for angle of repose, bulk density, compressibility index, total porosity, and drug content. The tablets were subjected to thickness, diameter, weight variation test, drug content, hardness, friability, and in vitro release studies. The granules showed satisfactory flow properties, compressibility, and drug content. All the tablet formulations showed acceptable pharmacotechnical properties and complied with in-house specifications for tested parameters. According to the theoretical release profile calculation, a oncedaily sustained-release formulation should release 5.92 mg of nicorandil in 1 hour, like conventional tablets, and 3.21 mg per hour up to 24 hours. The results of dissolution studies indicated that formulation F-I (drug-to-HPMC, 1[ratio]4; ethanol as granulating agent) could extend the drug release up to 24 hours. In the further formulation development process, F-IX (drug-to-HPMC, 1[ratio]4; EC 4% wt/vol as granulating agent), the most successful formulation of the study, exhibited satisfactory drug release in the initial hours, and the total release pattern was very close to the theoretical release profile. All the formulations (except F-IX) exhibited diffusion-dominated drug release. The mechanism of drug release from F-IX was diffusion coupled with erosion.

Keywords: nicorandil, hydroxypropyl methylcellulose, ethylcellulose, sustained release, matrix tablets

Full Text

The Full Text of this article is available as a PDF (491K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Frydman MA, Chapelle P, Diekmann H. Pharmacokinetics of nicorandil. Am J Cardiol. 1989;20:25J–33J. doi: 10.1016/0002-9149(89)90201-4. [PubMed] [Cross Ref]
2. Leonetti G, Fruscio M, Gradnik R, Chianca R, Bolla GB, Prandi P, Zanchetti A. Nicorandil, a new vasodilator drug, in patients with essential hypertension. J Hypertens. 1989;7:S292–S293. [PubMed]
3. Camm AJ, Maltz MB. A controlled single-dose study of the efficacy, dose response and duration of action of nicorandil in angina pectoris. Am J Cardiol. 1989;20(63):61J–65J. doi: 10.1016/0002-9149(89)90207-5. [PubMed] [Cross Ref]
4. Lordi GN. Sustained release dosage forms. In: Lachman L, Liberman HA, Kanig JL, editors. The Theory and Practice of Industrial Pharmacy. Mumbai, India: Varghese Publishing House; 1987. pp. 430–456.
5. Cooper J, Gunn C. Powder flow and compaction. In: Carter SJ, editor. Tutorial Pharmacy. New Delhi, India: CBS Publishers and Distributors; 1986. pp. 211–233.
6. Shah D, Shah Y, Rampradhan M. Development and evaluation of controlled release diltiazem hydrochloride microparticles using cross-linked poly(vinyl alcohol) Drug Dev Ind Pharm. 1997;23(6):567–574.
7. Aulton ME, Wells TI. Pharmaceutics: The Science of Dosage Form Design. London, England: Churchill Livingstone; 1988.
8. Martin A. Micromeritics. In: Martin A, editor. Physical Pharmacy. Baltimore, MD: Lippincott Williams & Wilkins; 2001. pp. 423–454.
9. Pharmacopoeia of India. New Delhi: Ministry of Health and Family Welfare, Government of India, Controller of Publications; 1996.
10. Rawlins EA. Bentley's Text Book of Pharmaceutics. London, England: Cassell and Collier MacMillan; 1977.
11. Andersson KE. Clinical pharmacology of potassium channel openers. Pharmacol Toxicol. 1992;70:244–254. doi: 10.1111/j.1600-0773.1992.tb00466.x. [PubMed] [Cross Ref]
12. Frampton N. Review of nicorandil and pharmacology and therapeutic efficacy in angina. Drugs. 1992;44:625–655. doi: 10.2165/00003495-199244040-00008. [PubMed] [Cross Ref]
13. Banker GS, Anderson LR. Tablets. In: Lachman L, Liberman HA, Kanig JL, editors. The Theory and Practice of Industrial Pharmacy. Mumbai, India: Varghese Publishing House; 1987. pp. 293–345.
14. Kibbe HA. Hand Book of Pharmaceutical Excipients. London, England: American Pharmaceutical Association, Pharmaceutical Press; 2000.
15. Mutalik S, Hiremath D. Formulation and evaluation of chitosan matrix tablets of nifedipine. The Eastern Pharmacist. 2000;2:109–111.
16. Michailova V, Titeva S, Kotsilkova R, Krusteva E, Minkov E. Water uptake and relaxation processes in mixed unlimited swelling hydrogels. Int J Pharm. 2000;209:45–56. doi: 10.1016/S0378-5173(00)00536-6. [PubMed] [Cross Ref]
17. Khan KA, Rhodes CT. Evaluation of different viscosity grades of sodium carboxy methylcellulose as tablet disintegrants. Pharm Acta Helv. 1975;50:99–102. [PubMed]
18. Shah NH, Lazarus JH, Jarwoski CL. Carboxy methylcellulose: Effect of degree of polymerization and substitution on tablet disintegration and dissolution. J Pharm Sci. 1981;70(6):611–613. doi: 10.1002/jps.2600700609. [PubMed] [Cross Ref]
19. Hogan JE. Hydroxypropyl methylcellulose sustained release technology. Drug Dev Ind Pharm. 1989;15(27):975–999. doi: 10.3109/03639048909043660. [Cross Ref]
20. Higuchi T. Mechanism of sustained action medication. Theoretical analysis of rate release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963;52:1145–1149. doi: 10.1002/jps.2600521210. [PubMed] [Cross Ref]
21. Korsmeyer RW, Gurny R, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15:25–35. doi: 10.1016/0378-5173(83)90064-9. [Cross Ref]
22. Fassihi RA, Ritschel WA. Multiple layer, direct compression controlled release system: In vitro and in vivo evaluation. J Pharm Sci. 1993;82:750–754. doi: 10.1002/jps.2600820715. [PubMed] [Cross Ref]

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists