Preparation And Performance Research Of Rifampicin And Isoniazid Compound Drug-Loaded Fibers

As the first-line drugs for the treatment of tuberculosis,the insoluble rifampicin(RIF)has a lower oral bioavailability than water-soluble isoniazid(INH),but the rapid absorption of INH is accompanied by greater drug resistance caused by long-term use alone.The combination of the two drugs can greatly improve the therapeutic effect and reduce resistance,but the direct mixing of RIF and INH will aggravate the degradation of RIF.Electrospinning technology can prepare micro-nano fibers with super specific surface area and high porosity,which has been widely used in biomedical field.In this paper,RIF and INH were selected as the research objects,and three electrospinning techniques were used to prepare compound drug-loaded fibers which carried two drugs,and its properties were studied:Polyvinylpyrrolidone(PVP)was selected as a carrier,and solutions were prepared respectively with RIF and INH to prepare RIF-INH-PVP compound fiber(RIPCF)and two single fibers RIF-PVP and INH-PVP.RIPCF was a blending system of two single fibers.In the process of spinning,RIF and INH changed from crystalline to amorphous state without chemical reaction with PVP,but the INH and PVP formed a low eutectic mixture.The INH-PVP fibers made RIPCF more hydrophilic than RIF-PVP fibers.The release time of RIF from the fiber was half that of the powder,which improves the bioavailability of the drug.Polylactic acid(PLLA)was selected as the carrier and span 80 as the emulsifier,coaxial electrospinning and emulsion electrospinning were used to prepare compound drug-loaded fibers with RIF on the shell and INH in the core under the same spinning conditions respectively.And the influence of span80 concentration,water-oil volume ratio and emulsification time on emulsion formulation were explored.When the INH concentration decreased,the core layer diameter of coaxial fibers gradually decreases,but that of emulsion fibers gradually increases.PLLA in fibers changed from semi-crystalline to amorphous state,and part of the RIF and INH in the coaxial fiber became amorphous,while the other part retained the crystal characteristics.In emulsion fibers,both RIF and INH became amorphous without chemical reaction with PLLA.The coaxial fibers can only dissolve up to 40%of RIF and 18%of INH in about 6 hours.By the action of the hydrophilic end of span80,the emulsion fibers can dissolve more than 85%of RIF and more than 20%of INH in 3 hours.In this paper,the compound quick-release fibers can improve the bioavailability of RIF,and the core-shell structured sustained-release compound fibers can maintain a stable blood concentration and avoid the damage caused by burst release and rapid metabolism.The three kinds of fibers alleviate the degradation of RIF caused by the contact with INH and RIF,fill the gap of electrospun tuberculosis compound drugs,and have profound significance and value.