| Poor patient compliance is the most common reason for the failure of chemotherapy of tuberculosis. One useful method to ensure compliance in tuberculosis patients is to administer the drugs in carriers/delivery systems that release drugs in a sustained manner at therapeutic concentrations over a period of time. This strategy helps to improve patient compliance in terms of reducing the dosage frequency, and may also minimize the risk of emergence of drug-resistant mutants and potential toxicity.Sodium alginate, a salt of alginic acid (brown algae), a linear copolymer of guluronic acid and mannuronic acid, has the ability to form a gel/meshwork in the presence of divalent cations such as CaCl2. This gel shrinks at acidic pH and erodes at alkaline pH. Therefore, it can be used effectively to deliver drugs to the intestine. Moreover, alginate is mucoadhesive and is likely to stick to intestinal mucosa for prolonged periods of time.Alginate microspheres were developed as oral sustained delivery carriers for antitubercular drugs in order to improve patient compliance.The method of electrostatic drop generation was used to produce rifampicin-loaded microspheres with sodium alginate and stearic acid. The shape and sizes of drug-loaded particles were measured by an optical microscope. RFP was estimated by spectrofluorimetry in vitro.We used a single-factor experiment to investigate the influence on partical size and entrapment efficiency. Factors included the concentration of sodium alginate, the ratio of sodium alginate to rifampicin, the ratio of stearic acid, and the cross-linking time. The mean particle size of the microspheres increased with an increase in the concentration of polymer.The increase in the concentration of stearic acid and sodium alginate caused the increase in the entrapment efficiency and the extent of drug release. The cross-linking time shorter than 20minutes resulted in higher entrapment efficiencies. The microspheres were well spherically made.The mean diameter, entrapment efficiency and loading efficiency was70.2μm, 83.5% and 17.1% respectively.The release profiles of RFP from microspheres were examined in simulated gastric fluid (SGF pH 1.2) and simulated intestinal fluid (SIF pH 7.4) without enzyme.Only 50% of the encapsulated RFP was released in the SGF throughout 55hours. In the SIF, RFP was released quickly during the first 5 hours, and then there was slow but sustained release until 96.8%was released at the 55th hour. The concentration of sodium alginate and the presense of stearic acid had great affect on the release of RFP.Then the pharmacokinetics of alginate microspheres encapsulated rifampicin was examined in rats. A HPLC method was developed to determine the drug content in blood. RFP- microspheres exhibited sustained release for 36 hours in plasma. Peak plasma concentration (Cmax), Tmax, elimination half-life (t1/2e) and AUC0 of alginate drug were significantly higher than those of free drugs.It suggests that oral application of alginate-encapsulated drugs could be useful in the effective treatment of tuberculosis, resulting in improved compliance by the patients.It can offer a hope for a better future to the management of tuberculosis.
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