Preparation And Evaluation Of Sustained-release Microspheres Isoniazid

The purpose of this study was to design a sustained release drug delivery system of isoniazid using polylactic acid (PLA) as the main material. The drug delivery system was expected to be used in fiberoptic bronchoscopy-interventional therapy of anti-tuberculosis for the purpose of sustaining the drug release and to help maintain a therapeutic concentration of anti-tuberculosis agent.Isoniazid-polylactic acid microspheres (IN-PLA-MS) and isoniazid-chitosan-polylactic acid microspheres (IN-CTS-PLA-MS) were prepared by spray drying method. Besides, the basic characteristics and the in vitro release in PBS (pH7.4,37℃) were studied, and the in vivo release character in SD rats of IN-PLA-MS was also studied.Firstly, the high-performance liquid chromatography (HPLC) detect method of IN was established. And the physical and chemical properties of IN, including water-solubility, oil-water partition coefficients and stability were studied. The HPLC method had high sensitivity and good reproducibility, which was suitable for detection of IN. And IN was stable under the experimental condition of light, humidity, high temperature, and the IN solutions at pH of3,5,7,9,11were relatively stable within24h.Secondly, IN-PLA-MS was prepared by solid in oil(S/O) spray drying method. The morphology, particle size distribution, thermo property of microspheres were evaluated. Results indicated that the microspheres prepared were spherical, smooth and individually homogeneously distributed with mean diameter of5.62μm Which entrapment efficiency (EF) and drug loading rate (DL) was (89.32±1.21)%and (5.43±0.26)%, repectively. In vitro release study showed a sustained release profile for at least23days with low initial burst.Thirdly, IN-CTS-PLA-MS was prepared. The mean diameter of which was4.64μm and the DL was (17.76±1.42)%, which was2.3times higher than IN-PLA-MS. The EF was (5.43±0.26)%. In vitro release study showed a sustained release profile for at least7days.Finally, the in vivo drug release of IN-PLA-MS was investigated. The drug in lung of SD rats was extracted by bronchoalveolar lavage fluid and its concentration was determined by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Drug concentration in rat lungs could maintain in a relatively stable concentration from1d to14d after administration. And the drug concentration was32.71ng·mL-1, which was higher than the minimum inhibitory concentration (MIC)25 ng·mL-1In summary, the two kinds of microspheres prepared can basically meet the purpose of this study, which were supposed to be helpful for fiberoptic broncho scop y-interventional therapy of anti-tuberculosis. Besides, S/O-spray drying method used in this study was simple and easy to control, which was an effective method to prepare sustained release microspheres loading low molecule water-soluble drugs.