Formulation development and evaluation of Rifampicin niosome for anti-tubercular treatment with isoniazid

Suriyaprakash, T N K (2009) Formulation development and evaluation of Rifampicin niosome for anti-tubercular treatment with isoniazid. Doctoral thesis, (Synopsis) The Tamilnadu Dr. M.G.R. Medical University, Chennai.


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INTRODUCTION : With approximately 3 million annual deaths in the 1990s, tuberculosis remains a leading cause of mortality worldwide into the 21st century. It is estimated that onethird 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 drugs (Smith et al., 2004). 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. AIM : The aim is to find a dosage regimen for the treatment of tuberculosis using sustained dosage of rifampicin loaded in niosome vesicles administered intraperitonially and oral dosing of isoniazid. Formulations were developed in such a way as (i) to provide sustained programmed release of the drugs in order to circumvent the multiple dosing required for conventional therapy and (ii) to provide a means of delivery of the drugs to the macrophages where mycobacteria reside during an infection (Aarthi J and Deepthi I 2001; Abazinge MT et al., 2000 and Agnishwar G 2006). Rifampicin and isoniazid were both first-line drugs used in the therapy of tuberculosis and are included in the list of recommended drug regimens for treatment of latent M. Tuberculosis infection in adults (Ahmed SG et al., 2005 and Aliasgar S and Misra A 2002). They have been used in combination for treatment of tuberculosis in clinical trials of human immunodeficiency virus-negative and human immunodeficiency virus-positive persons. As a part of this study, the use of rifampicin-loaded niosomes in a combined therapeutic regimen with oral dosages of isoniazid were studied and evaluated. OBJECTIVE : Although directly observed treatment - Short course (DOTS), contributes for the control of the tuberculosis, non compliance with treatment continues to be the main cause of poor results (Arachi A 1991 and American Thoracic Society Documents 2002). The main reason for non - compliance is the long, 6 - month duration of the treatment. Hence shortening of the duration of treatment without compromising the cure and relapse rates still remains a major goal for control policies. The drugs of choice and first line of treatment for tuberculosis are rifampicin and isoniazid. By using these two drugs with different approach, it is presumed that the dose level of these two drugs will be reduced and also the time period of treatment. Another difficulty with the treatment of the tuberculosis is Multidrug Resistant – Tuberculosis i.e. MDR-TB (Sharma SK 2004). With this approach of reduced dose and duration, it is possible to enhance chemotherapy and more importantly improve patient compliance, which is rather a prime factor for the failure of tuberculosis treatment. The objectives of this extended study were, therefore, to (i) perform preformulation studies of the formulations (ii) prepare niosome formulations of rifampicin using various surfactants (iii) increase the drug loading of the small niosomes, (iv) test their ability to treat an M. Tuberculosis infection in an animal model without the use of the larger niosome formulations, and (v) evaluate the level of activity of combined therapy with the rifampicin-loaded small niosomes and an oral regimen of another antimycobacterial drug, isoniazid, by performing histopathological studies. MATERIALS & METHODS : The niosomes were prepared with various ratios of surfactants, cholesterol and dicetyl phosphate. The formulation which produced better physicochemical characteristics, maximum entrapment and drug release with highest duration of release was selected for further studies. The ratio of surfactant, cholesterol and dicetyl phosphate that was employed was 47.5:47.5:5. These ingredients were dissolved in diethyl ether (10-15 ml). The solvent was evaporated under reduced pressure at a temperature of about 60°C using a rotary flash evaporator. This temperature was achieved by rotating the round bottom flask, under reduced pressure, about 1.5 cm above a boiling water bath, leaving a thin layer of solid mixture deposited on the wall of the round bottom flask. The 10ml of 1mg/ml solution was added to the flask heated to about 50°C on the water on a vortex, until a good dispersion of the mixture was obtained. The suspension was then sonicated for 15 minutes to form unilamellar niosomes. CONCLUSION : A therapeutic regimen with the rifampicin niosomes in combination with oral regimens of isoniazid was able to safely increase the effective therapeutic range of Isoniazid. In most cases, combination therapy reduced the appearances of lesion in the lungs, spleens 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)
Uncontrolled Keywords: Formulation development, evaluation, Rifampicin niosome, anti-tubercular treatment, isoniazid.
Subjects: PHARMACY > Pharmaceutics
Depositing User: Subramani R
Date Deposited: 20 Aug 2017 12:41
Last Modified: 24 Oct 2022 14:22

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