Purpose The purpose of present study is to formulate microemulsion composed of oleic acid, phosphate buffer, Tween 80, ethanol and
to investigate its potential as drug delivery system for an antitubercular drug isoniazid.
Materials and Methods The pseudo-ternary phase diagram (Gibbs Triangle) was delineated at constant surfactant/co-surfactant ratio (Km 0.55). Changes
in the microstructure were established using conductivity (σ), viscosity (η), surface tension (γ) and density measurements.
Dissolution studies and particle size analysis were carried out to understand the release of isoniazid from the microemulsion
formulation. Further, partitioning studies and spectroscopic analysis (FT-IR and 1H NMR) was performed to evaluate the location of drug in the colloidal formulation.
Results Physico-chemical analysis of microemulsion system showed the occurrence of structural changes from water-in-oil to oil-in-water
microemulsion. It has been observed that the microemulsion remained stable after the incorporation of isoniazid (in terms
of optical texture, pH and phase separation). The changes in the microstructure of the microemulsion after incorporation of
drug was analyzed on the basis of partition studies of isoniazid in microemulsion components and various parameters viz pH,
σ, η,γ. In addition, the particle size analysis indicates that the microemulsion changes into o/w emulsion at infinite dilution.
The spectroscopic studies revealed that most of the drug molecules are present in the continuum region of an o/w microemulsion.
Dissolution studies infer that a controlled release of drug is expected from o/w emulsion droplet. In the present system the
release of isoniazid from microemulsion was found to be non-Fickian.
Conclusion The present Tween based microemulsion appears beneficial for the delivery of the isoniazid in terms of easy preparation, stability,
low cost, sustained and controlled release of a highly water soluble drug.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
BACKGROUND AND PURPOSE: Rifampicin has been extensively reported to exacerbate the hepatotoxicity of isoniazid in patients with tuberculosis. However, this was controversially claimed by previous reports using rat models. This study evaluated the effect of rifampicin on isoniazid-induced hepatocyte toxicity by using human and rat hepatocytes in tissue-like culture.EXPERIMENTAL APPROACH: Hepatocytes in tissue-like gel entrapment were used to examine isoniazid toxicity, as shown by cell viability, intracellular glutathione content and albumin secretion. For demonstration of the differential effects of rifampicin on human and rat hepatocytes, induction by rifampicin of cytochrome P450 (CYP) 2E1, a major enzyme associated with isoniazid hepatotoxicity, was detected by 4-nitrocatechol formation and RT-PCR analysis.KEY RESULTS: Rifampicin (12 microM) enhanced isoniazid-induced toxicity in human hepatocytes but not in rat hepatocytes. Enhanced CYP 2E1 enzymic activity and mRNA expression were similarly detected in human hepatocytes but not in rat hepatocytes. Both rat and human hepatocytes in gel entrapment were more sensitive to isoniazid treatment compared with the corresponding hepatocytes in a monolayer culture.CONCLUSIONS AND IMPLICATIONS: The difference in induction of CYP 2E1 by rifampicin between rat and human hepatocytes accounted for the difference in exacerbation of isoniazid hepatocyte toxicity by rifampicin, with more significant toxicity in gel entrapment than in monolayer cultures. Thus, human hepatocytes in tissue-like cultures (gel entrapment) could be an effective model for hepatotoxicity research in vitro, closer to the in vivo situation. 相似文献
Isoniazid (INH) is a first-line antitubercular drug. We report a case of a patient who developed a pleural effusion 2 months after starting antitubercular treatment for spinal tuberculosis. Isoniazid was found to be the culprit and its discontinuation caused subsidence of the effusion. 相似文献
Background: Tuberculosis (TB) remains a main cause of morbidity and mortality among individuals infected with HIV. We investigated the incidence of TB among a cohort of HIV infected patients attending a setting with low TB burden where screening for latent TB infection is not routinely carried out.
Methods: an observational cohort study on HIV-infected adults attending the HIV clinic at Queen Elizabeth Hospital Birmingham, UK between 1 January 2011 and 30 September 2015. Patients with culture-proven TB after HIV diagnosis, or those treated for clinical diagnosis of the infection, were classified as having “active TB”.
Results: 1824 patients were included in the study (5347 patient years of follow up), of whom 21 patients developed TB (16 microbiology confirmed). Of the 666 new HIV diagnoses, six patients developed TB within one month, giving a TB prevalence at the time of HIV diagnosis of 0.9%. The total TB incidence for the remaining 1818 patients was 2.81 cases per 1000 patient years (95% CI: 1.63–4.53). TB incidence was significantly more common among patients with CD4 ≤ 200 cells/mm3 compared to those with CD4 > 500 cells/mm3 (28.2 vs. 1.22 per 1000 patient years, p < 0.001), and in patients with VL ≥ 40 copies/mL compared to <40 copies/mL (8.30 vs. 1.42, p < 0.001).
Conclusion: In settings with low TB prevalence, early start of combined antiretroviral therapy and intensified TB case finding protocols may significantly reduce the incidence of TB. 相似文献
Diagnosing and treating latent tuberculosis (TB) infection (LTBI) is recognized by the World Health Organization as an important strategy to accelerate the decline in global TB and achieve TB elimination. Even among low‐TB burden countries that have achieved high rates of detection and successful treatment for active TB, a number of barriers have prevented implementing or expanding LTBI treatment programmes. Of those infected with TB, relatively few will develop active disease and the current diagnostic tests have a low predictive value. LTBI treatment using isoniazid (INH) has low completion rates due to the long duration of therapy and poor tolerability. Both patients and physicians often perceive the risk of toxicity to be greater than the risk of reactivation TB. As a result, LTBI treatment has had a limited or negligible role outside of countries with high resources and low burden of disease. New tools have emerged including the interferon‐gamma release assays that more accurately diagnose LTBI, particularly in people vaccinated with Bacillus Calmette–Guerin (BCG). Shorter, better tolerated treatment using rifamycins are proving safe and effective alternatives to INH. While still imperfect, TB prevention using these new diagnostic and treatment tools appear cost effective in modelling studies in the United States and have the potential to improve TB prevention efforts globally. Continued research to understand the host–organism interactions within the spectrum of LTBI is needed to develop better tools. Until then, overcoming the barriers and optimizing our current tools is essential for progressing toward TB elimination. 相似文献