Preparation Of Uniform Clarithromycin Nanoparticles Using Subcritical Water

In the field of medicine, poorly water soluble drugs occupy a large proportion, about 40%. The solubility of the drug in the body is extremely low, resulting in most of the drugs with the metabolism of human body eduction body outside, waste caused by drugs, resulting in waste of drugs. As a result, increase the solubility of poorly water soluble drugs is very important. The study found that the drug particles size has a great influence for the solubility of a drug. The indissolvable drug solubility is inversely proportional with the drug to the size of the particle size. Therefore, through the use of appropriate method to smaller particle size, morphology, uniform drug particles, which can conducive to the absorption of drugs in the human body, increase the quantity into the systemic circulation, avoid unnecessary waste of drugs. There are many kinds of ways of preparation of nano drugs, such as physical crushing method, high pressure homogenizing method, microemulsion method, solvent-desolvation method, etc. Solvent-desolvation method was the commonly used method of preparation of nano drug in recent years. Compared with other methods, the solvent-desolvation method has great advantage. However, the method uses organic solvents, the removal of the organic solvent is complex and pollute the environment, the subcritical water (SBCW) is a good solution to the problem. As solvent, subcritical water has the advantages of non-toxic, non-polluting, green environmental protection, and its polarity can be control. This article through studied poorly water soluble drugs dissolution of clarithromycin in subcritical water, got a lot of solubility data and set up the appropriate mathematical model, studied the process conditions and influence factors of preparation of clarithromycin nanoparticles in subcritical water.Clarithromycin (CLA) in subcritical water solubility research, first, we investigated the effect of equilibrium time on the solubility of clarithromycin in subcritical water found that under the same temperature and pressure, the solubility of clarithromycin increased with the extension of balance time, the temperature between 100? to 180? dissolve balance time is different, the final 20min to dissolve balance time. Second, we investigated the subcritical water pressure influence on clarithromycin solubility, the experimental results showed that under varying pressure, solubility of clarithromycin was almost unchanged, showing that pressure did not affect the solubility of clarithromycin in subcritical water. Finally the influence of subcritical water temperature and cosolvent content on the solubility of clarithromycin was inspected; the experimental results showed an increase in clarithromycin solubility with increasing temperature. The addition of cosolvent to clarithromycin increase solubility, and increases with the increase of content.Preparation of clarithromycin nanoparticles subcritical water research, respectively investigated the influence of multiple factors on the clarithromycin nanoparticles, the optimal experimental conditions were determined:subcritical water temperature 150?, the anti-solvent temperature 0?, subcritical water/anti-solvent volume ratio 1:3, HPMC, PEG, a-lactose and PVP mass concentration was 0.4%. In the optimized experimental conditions, clarithromycin nanoparticle size was less than 80nm. Infrared spectra showed that after subcritical water treated clarithromycin chemical structure has not changed, x-ray diffraction (XRD) results showed that after subcritical water treated clarithromycin diffraction peak intensity weakened, suggested that drug crystallinity decreased. The dissolution rates with CLA nanoparticles displayed more effective than the raw drug. After 150 min, approximately 88.83% of the CLA nanoparticles dissolved, respectively, while only 10.61% of the raw drug dissolved.