Highly efficient and long-acting slow-release formulation of poorly soluble drugs and preparation method thereof

A method for preparing a high-efficacy, long-acting slow-release formulation of the poorly soluble drug, comprising the following steps:

• step 1. taking the poorly soluble drug 1 g, povidone K30 1-3 g, soybean lecithin 0.3-0.8 g and acrylic resin IV 0.2-0.5 g and injecting in absolute ethyl alcohol 20-40 ml (70° C. water-bath can be adopted to accelerate dissolution if necessary);
• after the said materials having dissolved, treating the solution with 60° C. water-bath;
• then rotarily evaporating the solution at 90 rpm, and then treating the substance with 70° C. water-bath till the solvent completely evaporates;
• putting the substance so obtained into a −20° C. freezer for 2 hours and then into a 60° C. drying oven for 12 hours;
• comminuting the substance and sieving it with 80 mesh;
• the solid dispersion of the poorly soluble drug is therefore obtained and ready for later use;
• step 2. taking cyclohexane 20-80 ml, nonyl phenol 10(NP-10) 4-8 ml and mixing them together;
• adding in-n-hexanol 1-3 ml, 25.6% ammonia water 1-3 ml and agitating for 1 hour at room temperature;
• slowly dropping in tetraethyl orthosilicate 3-5 ml and agitating for 24 hours at room temperature;
• adding in absolute ethyl alcohol 40-80 ml and-treating with ultrasound for 1 hour;
• and then centrifugally separating at 15000 rpm for 15 min and washing the precipitate with distilled water three times;
• adding water, freezing and drying the substance in succession, and silica nanoparticles 8 g-32 g are therefore obtained;
• taking the said silica nanoparticles 1 g, adding in 0.6 mol/L Na2CO3 solution 1000 ml, treating with ultrasound for 4-5 min under the condition of 60-70° C., 200 W, and then centrifugally separating at 15000 rpm for 15 min;
• and washing the precipitate with distilled water three times;
• adding in distilled water 10 ml, freezing and drying the substance in succession, and mesoporous silica nanoparticles are therefore obtained;
• dissolving the poorly soluble drug 2 g in absolute ethyl alcohol 10-20 ml, soaking mesoporous silica nanoparticles 1 g in the solution for 24 hours, and then centrifugally separating at 15000 rpm for 15 min and washing the precipitate with absolute ethyl alcohol three times;
• adding in distilled water 10 ml, freezing and drying the substance in succession, and drug-loaded nanoparticles are therefore obtained;
• step 3. taking solid dispersion of the poorly soluble drug 1 g, mixing it with hypromellose K4M 0.2-0.3 g and L-HPC 0.1-0.2 g, sieving with 16 mesh and the wet granules so obtained are baked at 60° C. for 30 min, reshaping the granules with 16 mesh and the slow-release granules 1 are therefore obtained;
• step 4. taking solid dispersion of the poorly soluble drug 1.8 g, mixing it with hypromellose K4M 0.1-0.2 g, L-HPC 0.2-0.3 g and drug-loaded silica nanoparticles 1.25-2.5 g;
• sieving with 16 mesh and the wet granules so obtained are baked at 60° C. for 30 min, reshaping the granules with 16-mesh and the slow-release granules 2 are therefore obtained;
• step 5. mixing the slow-release granules 1 and the slow-release granules 2 at the ratio of 1:2.75˜1:4;
• and-then tableting the mixed granules with the force around 40-60N;
• the high-efficacy, long-acting, slow-release tablet of the poorly soluble drug disclose in this invention is therefore obtained.