Suriyaprakash, T N K (2010) Formulation Development and Evaluation of Rifampicin Niosomes for Anti-tubercular treatment with Isoniazid. Doctoral thesis, The Tamilnadu Dr. M.G.R. Medical University, Chennai.
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Abstract
With approximately 3 million annual deaths in the 1990’s, tuberculosis remains a leading cause of mortality worldwide into the 21st century. It is estimated that one-third of the world population harbour a latent infection by the causative pathogen, Mycobacterium tuberculosis (M. tuberculosis). One of the hallmarks of tuberculosis (TB) is the persistent phase of infection. During this phase the bacteria are thought to be in a slow growing or non-growing state and are recalcitrant to treatment by conventional anti-TB drugs1. One of the drawbacks of existing TB drugs is that they target actively growing bacteria in cell processes such as cell wall biogenesis and chromosome replication only. Patients who carry a latent infection are at risk of reactivation of this disease and this factor which causes a major obstacle to the global control of TB. To treat an infection, a cocktail of drugs including, for example, isoniazid, rifampicin, ethambutol and pyrazinamide are prescribed for 2 months followed by a continuation phase in which isoniazid and rifampicin are taken2, 3. Long-term therapies lasting between 6 and 9 months have frequently led to patient non-compliance and, in turn, contributed to the emergence of multi-drug resistant TB (MDR-TB). MDR strains, such as the notorious Strain W, are increasingly being found which are resistant to many first-line agents including isoniazid, rifampicin, ethambutol, streptomycin and pyrazinamide, as well as some of the secondline drugs, such as ethionamide, cycloserine, thiacetazone and the quinolone derivatives. The cost of treating a patient carrying MDR-TB is much greater, typically running into tens of thousands of dollars per patient, than for patients carrying a drug-sensitive strain. Without effective treatments, the fear is that the number of infections caused by MDR-TB will increase out of control. From the preliminary work, it was observed that, span 60 niosomes was better than that of span 20, span 40 and span 80 niosomes. It was also evident that better entrapment efficiency of above 50% was achieved in this project. In vitro release of the niosomes with various surfactants was studied. The niosomes prepared with span 60 gave prolonged release and more amount of drug was released than with other surfactants. In vivo characteristics of sterilized rifampicin niosomes prepared with span 60 was administered intraperitoneally along with isoniazid oral dose to mice. Isoniazid with a minimum dose of 1.56 mg/kg for 26 days orally along with minimum 50 mg dose of rifampicin niosomes on 0 and 7 days administered intraperitoneally produced excellent result in histopathological studies in liver, lungs and spleen. In terms of storage stability, span 60 niosomes when stored at 45 °C 75% RH, exhibited a drug leak of less than 10 % even after 6 months of storage. CONCLUSION: A therapeutic regimen with the rifampicin niosomes in combination with oral regimens of isoniazid was able to safely eliminate the lesions from lungs, liver and spleen. In most cases, combination therapy reduced or eliminated the appearances of lesion in the lungs, spleen and liver to non detectable levels, something not achieved with the oral regimen of isoniazid alone. The results were achieved by using a much reduced dosing schedule for rifampicin. Instead of dosing the mice daily 26 days, as would be the case with an oral dose, administration of dose to the mice only twice during that period and achieve significant improvement of the isoniazid oral therapy. These findings are encouraging and demonstrative that niosome technology can be safely used in combination with another antimicrobial agent. With the addition of the results presented in this report, it seems apparent that niosome technology can offer an alternative therapy for treatment of tuberculosis.
| Item Type: | Thesis (Doctoral) |
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| Uncontrolled Keywords: | Formulation, development, evaluation, Rifampicin niosomes, isoniazid, anti-tubercular treatment. |
| Subjects: | PHARMACY > Pharmaceutics |
| Depositing User: | Devi S |
| Date Deposited: | 27 Jun 2017 07:31 |
| Last Modified: | 16 Sep 2022 02:13 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/421 |
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