Search tips
Search criteria 


Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
AAPS PharmSciTech. 2007 September; 8(3): E133–E139.
Published online 2007 August 24. doi:  10.1208/pt0803068
PMCID: PMC2750562

A novel solid dosage form of rifampicin and isoniazid with improved functionality


The aim of the present investigation was to develop a novel dosage form of rifampicin and isoniazid to minimize degradation of rifampicin in acidic medium and to modulate the release of rifampicin in the stomach and isoniazid in the intestine. Gastroretentive tablets of rifampicin (150 mg) were prepared by the wet granulation method using hydroxypropyl methylcellulose, calcium carbonate, and polyethylene glycol 4000. The granules and tablets of rifampicin were characterized. Hard gelatin capsules (size 4) containing a compacted mass of isoniazid (150 mg) and dicalcium phosphate (75 mg) were enteric coated. Two tablets of rifampicin and 1 capsule (size 4) of isoniazid were put into a hard gelatin capsule (size 00). The in vitro drug release and in vitro drug degradation studies were performed. Rifampicin was released over 4 hours by zero-order kinetics from the novel dosage form. More than 90% of isoniazid was released in alkaline medium in 30 minutes. The results of dissolution studies with the US Pharmacopeia XXIII method revealed that a substantial amount of rifampicin was degraded from the immediate release capsule containing rifampicin and isoniazid powder owing to drug accumulation in the dissolution vessel and also to the presence of isoniazid. The degradation of rifampicin to 3-formyl rifampicin SV (3FRSV) was arrested (3.6%–4.8% degradation of rifampicin at 4 hours) because of the minimization of physical contact between the 2 drugs and controlled release of rifampicin in acidic medium in the modified Rossett-Rice apparatus. This study concludes that the problem of rifampicin degradation can be alleviated to a certain extent by this novel dosage form.

Keywords: Rifampicin, gastroretentive, isoniazid, enteric, dissolution, degradation

Full Text

The Full Text of this article is available as a PDF (311K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Blomberg B, Spinaci S, Fourie B, Laing R. The rationale for recommending fixed dose combination tablets for treatment of tuberculosis. Bull World Health Organ. 2001;79:1–1. [PubMed]
2. Shishoo CJ, Shah SA, Rathod IS, Savale SS, Kotecha JS, Shah PB. Stability of rifampicin in dissolution medium in presence of isoniazid. Int J Pharm. 1999;190:109–123. doi: 10.1016/S0378-5173(99)00286-0. [PubMed] [Cross Ref]
3. Singh S, Mariappan TT, Sharda N, Kumar S, Chakrabarti AK. The reason for an increase in decomposition of rifampicin in the presence of isoniazid under acid conditions. Pharm Pharmacol Commun. 2000;6:405–410.
4. Mariappan TT, Singh S. Regional gastrointestinal permeability of rifampicin and isoniazid (alone and their combination) in the rat. Int J Tuberc Lung Dis. 2003;7:797–803. [PubMed]
5. Gallo GG, Radaelli P. Rifampicin. In: Florey K, editor. Analytical Profiles of Drug Substances. New York, NY: Academic Press; 1976. pp. 467–575.
6. Prankerd RJ, Walters JM, Pames JH. Kinetics for degradation of rifampicin and azomethine-containing drug which exhibits reversible hydrolysis in acidic solutions. Int J Pharm. 1992;78:59–67. doi: 10.1016/0378-5173(92)90355-6. [Cross Ref]
7. Maggi N, Vigevani A, Gallo GG, Pasqualucci CR. Acetyl migration in rifampicin. J Med Chem. 1968;11:936–939. doi: 10.1021/jm00311a004. [PubMed] [Cross Ref]
8. Banker GS, Anderson NR. Tablets. In: Lachman L, Lieberman HA, Kanig JL, editors. The Theory and Practice of Industrial Pharmacy. 3rd ed. Philadelphia, PA: Lea & Febiger; 1990. pp. 316–317.
9. Martin A. Micromerities. In: Mundorff GH, Colaiezzi TJ, editors. Physical Pharmacy. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1999. pp. 446–448.
10. Rubinstein MH. Tablets. In: Aulton ME, editor. Pharmaceutics: The Science of Dosage Form. London, UK: Churchill Livingstone; 1998. pp. 304–310.
11. Carr RL. Evaluating flow properties of solids. Chem Eng. 1965;72:163–168.
12. Pharmacopeia US.National Formulary. USP 29-NF 24. Rockville, MD: USP; 2006.
13. Indian Pharmacopeia. Isoniazid.Indian Pharmacopoeia. vol. 1. Delhi, India: Controller of Publications; 1996;408-409.
14. Gohel MC, Mehta PR, Dave RK, Baraiya NH. A more relevant dissolution method for evaluation of floating drug delivery system. Dissolution Technol. 2004;11:22–25.
15. Bamba M, Puisievx F, Marty JP, Carstensen JT. Release mechanisms in gelforming sustained release preparations. Int J Pharm. 1979;2:307–315. doi: 10.1016/0378-5173(79)90037-1. [Cross Ref]
16. Rowe RC, Sheskey PJ, Weller PJ, editors. HPMC K4 M.Handbook of Pharmaceutical Excipients. 4th ed. London, UK: Pharmaceutical Press; 2003. pp. 297–299.
17. Gao P, Nixon PR, Skoug JW. Diffusion in HPMC gels, II: prediction of drug release rates from hydrophilic matrix extended release dosage forms. Pharm Res. 1995;12:965–971. doi: 10.1023/A:1016246028338. [PubMed] [Cross Ref]
18. Sung KC, Nixon PR, Skoug JW, et al. Effect of formulation variable on drug and polymer release from HPMC based matrix tablet. Int J Pharm. 2007;142:53–60. doi: 10.1016/0378-5173(96)04644-3. [Cross Ref]
19. Brewer GA. Isoniazid. In: Florey K, editor. Analytical Profiles of Drug Substances. New York, NY: Academic Press; 1977. pp. 183–258.
20. Lukulay P, Hokanson G. A perspective on reconciling mass balance in forced degradation studies. Pharm Technol. 2005;29:106–112.
21. Rang HP, Dale MM, Ritter JM, Moore PK. Pharmacology. London, UK: Churchill Livingstone; 2003. pp. 649–650.
22. Panchagnula R, Rungta S, Sancheti P, Agrawal S, Kaul C. In vitro evaluation of food effect on the bioavailability of rifampicin from antituberculosis fixed dose combination formulations. Farmaco. 2003;58:1099–1099. doi: 10.1016/S0014-827X(03)00161-7. [PubMed] [Cross Ref]
23. Khalil SAH, El-Khordagui LK, El-Gholmy ZA. Effect of antacids on oral absorption of rifampicin. Int J Pharm. 1984;20:99–106. doi: 10.1016/0378-5173(84)90221-7. [Cross Ref]

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