Login Register Cart 0
Generic placeholder image

Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Encapsulating Rifampicin into SLNs: A Viable Option for Managing its Bioavailability Issues Upon Co-Delivery with Isoniazid

Author(s): Harinder Singh, Ruchi Sood, Tridib Chaira, Alka Khanna, Dilip J Upadhaya, Ramesh Bambal, Pradip K. Bhatnagar, Mandeep Singh and Indu Pal Kaur*

Volume 17, Issue 4, 2020

Page: [343 - 347] Pages: 5

DOI: 10.2174/1567201817666200220121306

Price: $65

Abstract

Background: Rifampicin is known to degrade at the acidic pH of the stomach, especially in the presence of isoniazid. Although isoniazid also degrades partially, its degradation is reversible.

Objective: Presently, we provide a proof of the fact that the simultaneous oral administration of rifampicin (RIF), upon incorporation into solid lipid nanoparticles (RIF-SLNs), with isoniazid (INH) overcomes its INH-induced degradation and improves its oral bioavailability in rats.

Methods: Solid lipid nanoparticles of RIF (RIF-SLNs) were prepared using a novel and patented method. The effect of INH was investigated on in vivo bioavailability of RIF both in its free and encapsulated (RIF-SLNs) form, after oral administration to rats.

Results: Cmax and AUC0-∞ of RIF increased 158 % and 125 %, respectively, upon incorporation into SLNs versus free RIF when combined with INH. The Tmax decreased from 5.67 h to 3.3 h, and the plasma concentration of RIF remained above its MIC (8 μg/ml) at all the tested time points starting with 15 min, when administered as RIF-SLNs in combination with INH.

Conclusion: The results confirm the scope of combining RIF-SLNs with INH to overcome the bioavailability of free RIF when combined with INH, especially in fixed dose combinations.

Keywords: Oral bioavailability, drug interaction, oral administration, fixed dose combinations, Solid lipid nanoparticles, Isoniazid

« Previous Next »
Graphical Abstract

[1]
Frieden, T.R.; Sterling, T.R.; Munsiff, S.S.; Watt, C.J.; Dye, C. Tuberculosis. Lancet, 2003, 362(9387), 887-899.
[http://dx.doi.org/10.1016/S0140-6736(03)14333-4] [PMID: 13678977]
[2]
Shishoo, C.J.; Shah, S.A.; Rathod, I.S.; Savale, S.S.; Vora, M.J. Impaired bioavailability of rifampicin in presence of isoniazid from fixed dose combination (FDC) formulation. Int. J. Pharm., 2001, 228(1-2), 53-67.
[http://dx.doi.org/10.1016/S0378-5173(01)00831-6] [PMID: 11576768]
[3]
Anonymous, R. Rifampin. Tuberculosis (Edinb.), 2008, 88(2), 151-154.
[http://dx.doi.org/10.1016/S1472-9792(08)70024-6] [PMID: 18486058]
[4]
Mouton, R.P.; Mattie, H.; Swart, K.; Kreukniet, J.; de Wael, J. Blood levels of rifampicin, desacetylrifampicin and isoniazid during combined therapy. J. Antimicrob. Chemother., 1979, 5(4), 447-454.
[http://dx.doi.org/10.1093/jac/5.4.447] [PMID: 489492]
[5]
Doshi, B.S.; Bhate, A.D.; Chauhan, B.L.; Parkar, T.A.; Kulkarni, R.D. Pharmacokinetic interaction of oral RIF and INH in normal subjects. Indian Drugs, 1986, 23, 672-676.
[6]
Ellard, G.A.; Ellard, D.R.; Allen, B.W.; Girling, D.J.; Nunn, A.J.; Seng-Kee, T. The bioavailability of INH, RIF and Pyrazinamide in two commercially available combination formulations designed for use in the short course treatment of tuberculosis. Am. Rev. Respir. Dis., 1986, 133, 1076-1080.
[PMID: 3717760]
[7]
Acocella, G. Satellite symposium on quality control of antituberculosis drugs - human bioavailability studies. Bull IUATLD, 1989, 64, 38-40.
[8]
Fox, W. Drug combinations and the bioavailability of rifampicin. Tubercle, 1990, 71(4), 241-245.
[http://dx.doi.org/10.1016/0041-3879(90)90035-7] [PMID: 2267677]
[9]
Anonn, X. General policy topics. WHO drug info. World Health Organisation, 1991, 5, 39-40.
[10]
The promise and reality of fixed-dose combinations with rifampicin. A joint statement of the international union against tuberculosis and lung disease and the tuberculosis programme of the World Health Organization. Tuber. Lung Dis., 1994, 75(3), 180-181.
[PMID: 7919308]
[11]
Gallo, G.G.; Radaelli, P. Rifampicin. Analytical profile of drug substances; Florey, K., Ed.; Academic Press: New York, 1976, Vol. 5, pp. 467-515.
[12]
Prankerd, R.J.; Walters, J.M.; Parnes, J.H. Kinetics for degradation of rifampicin, an azomethine containing drug which exhibits reversible hydrolysis in acidic solutions. Int. J. Pharm., 1992, 78, 59-67.
[http://dx.doi.org/10.1016/0378-5173(92)90355-6]
[13]
Shishoo, C.J.; Shah, S.A.; Rathod, I.S.; Savale, S.S.; Kotecha, J.S.; Shah, P.B. Stability of rifampicin in dissolution medium in presence of isoniazid. Int. J. Pharm., 1999, 190(1), 109-123.
[http://dx.doi.org/10.1016/S0378-5173(99)00286-0] [PMID: 10528103]
[14]
Singh, S.; Mariappan, T.T.; Sharda, N.; Kumar, S.; Chakraborti, A.K. The reason for increase in decomposition of rifampicin in the presence of isoniazid under acid conditions. Pharm. Pharmacol. Commun., 2000, 6, 405-410.
[http://dx.doi.org/10.1211/146080800128736277]
[15]
Singh, H.; Bhandari, R.; Kaur, I.P. Encapsulation of Rifampicin in a solid lipid nanoparticulate system to limit its degradation and interaction with Isoniazid at acidic pH. Int. J. Pharm., 2013, 446(1-2), 106-111.
[http://dx.doi.org/10.1016/j.ijpharm.2013.02.012] [PMID: 23410991]
[16]
Singh, S.; Bhutani, H.; Mariappan, T.T.; Kaur, H.; Bajaj, M.; Pakhale, S. Behavior of uptake of moisture by drugs and excipients under accelerated conditions of temperature and humidity in the absence and the presence of light. 1. Pure anti-tuberculosis drugs and their combinations. Int. J. Pharm., 2002, 245(1-2), 37-44.
[http://dx.doi.org/10.1016/S0378-5173(02)00340-X] [PMID: 12270240]
[17]
Bhutani, H.; Mariappan, T.T.; Singh, S. Behaviour of uptake of moisture by drugs and excipients under accelerated conditions of temperature and humidity in the absence and the presence of light. Part II. Packaged and unpackaged anti-tuberculosis products. Pharm. Technol., 2003, 27, 44-45.
[18]
Sankar, R.; Sharda, N.; Singh, S. Behavior of decomposition of rifampicin in the presence of isoniazid in the pH range 1-3. Drug Dev. Ind. Pharm., 2003, 29(7), 733-738.
[http://dx.doi.org/10.1081/DDC-120021772] [PMID: 12906330]
[19]
Immanuel, C.; Gurumurthy, P.; Ramachandran, G.; Venkatesan, P.; Chandrasekaran, V.; Prabhakar, R. Bioavailability of rifampicin following concomitant administration of ethambutol or isoniazid or pyrazinamide or a combination of the three drugs. Indian J. Med. Res., 2003, 118, 109-114.
[PMID: 14700343]
[20]
Luyen, L.T.; Huyen, H.T.K.; Sang, T.V.; Huong, N.T.L. Effects of isoniazid and pyrazinamide on bioavailability of rifampicin when co-administered rifampicin-isoniazid-pyrazinamide. TTC Nghien Cuu Y Hoc, 2005, 36, 12-17.
[21]
Singh, H.; Jindal, S.; Singh, M.; Sharma, G.; Kaur, I.P. Nano-formulation of rifampicin with enhanced bioavailability: development, characterization and in-vivo safety. Int. J. Pharm., 2015, 485(1-2), 138-151.
[http://dx.doi.org/10.1016/j.ijpharm.2015.02.050] [PMID: 25769294]
[22]
Moretton, M.A.; Hocht, C.; Taira, C.; Sosnik, A. Rifampicin-loaded ‘flower-like’ polymeric micelles for enhanced oral bioavailability in an extemporaneous liquid fixed-dose combination with isoniazid. Nanomedicine (Lond.), 2014, 9(11), 1635-1650.
[http://dx.doi.org/10.2217/nnm.13.154] [PMID: 24410279]
[23]
Genina, N.; Boetker, J.P.; Colombo, S.; Harmankaya, N.; Rantanen, J.; Bohr, A. Anti-tuberculosis drug combination for controlled oral delivery using 3D printed compartmental dosage forms: From drug product design to in vivo testing. J. Control. Release, 2017, 268, 40-48.
[http://dx.doi.org/10.1016/j.jconrel.2017.10.003] [PMID: 28993169]
[24]
Kaur, I.P.; Singh, H. Inventors. Preparation of solid lipid nanoparticles of rifampicin to improve bioavailability and limiting drug interaction with isoniazid. Indian Patent Office Patent No.: 299469, 2013.
[25]
Garnham, J.C.; Taylor, T.; Turner, P.; Chasseaud, L.F. Serum concentrations and bioavailability of rifampicin and isoniazid in combination. Br. J. Clin. Pharmacol., 1976, 3(5), 897-902.
[http://dx.doi.org/10.1111/j.1365-2125.1976.tb00644.x] [PMID: 973984]
[26]
Kim, Y.; Lee, K.S.; Yoon, J.H.; Chung, M.P.; Kim, H.; Kwon, O.J.; Rhee, C.H.; Han, Y.C. Tuberculosis of the trachea and main bronchi: CT findings in 17 patients. AJR Am. J. Roentgenol., 1997, 168(4), 1051-1056.
[http://dx.doi.org/10.2214/ajr.168.4.9124114] [PMID: 9124114]
[27]
Peloquin, C.A. Using therapeutic drug monitoring to dose the antimycobacterial drugs. Clin. Chest Med., 1997, 18(1), 79-87.
[http://dx.doi.org/10.1016/S0272-5231(05)70357-9] [PMID: 9098612]
[28]
Ellard, G.A.; Fourie, P.B. Rifampicin bioavailability: a review of its pharmacology and the chemotherapeutic necessity for ensuring optimal absorption. Int. J. Tuberc. Lung Dis., 1999, 3(11)(Suppl. 3), S301-S308.
[PMID: 10593709]
[29]
Zwolska, Z.; Niemirowska-Mikulska, H.; Augustynowicz-Kopec, E.; Walkiewicz, R.; Stambrowska, H.; Safianowska, A.; Grubek-Jaworska, H. Bioavailability of rifampicin, isoniazid and pyrazinamide from fixed-dose combination capsules. Int. J. Tuberc. Lung Dis., 1998, 2(10), 824-830.
[PMID: 9783530]
[30]
Padgaonkar, K.A.; Revankar, S.N.; Bhatt, A.D.; Vaz, J.A.; Desai, N.D.; D’Sa, S.; Shah, V.; Gandewar, K. Comparative bioequivalence study of rifampicin and isoniazid combinations in healthy volunteers. Int. J. Tuberc. Lung Dis., 1999, 3(7), 627-631.
[PMID: 10423226]
[31]
Bhandari, R.; Kaur, I.P. Pharmacokinetics, tissue distribution and relative bioavailability of isoniazid-solid lipid nanoparticles. Int. J. Pharm., 2013, 441(1-2), 202-212.
[http://dx.doi.org/10.1016/j.ijpharm.2012.11.042] [PMID: 23220081]
[32]
Kakkar, V.; Singh, S.; Singla, D.; Kaur, I.P. Exploring solid lipid nanoparticles to enhance the oral bioavailability of curcumin. Mol. Nutr. Food Res., 2011, 55(3), 495-503.
[http://dx.doi.org/10.1002/mnfr.201000310] [PMID: 20938993]

Rights & Permissions Print Cite
Article Metrics
13
2
© 2024 Bentham Science Publishers | Privacy Policy