The Preparation Studies Of Hydroxyapatite-AminopHylline Nano-sized Compound Sustained-release Capsules

Hydroxyapatite is a human and animal bones, teeth, the importance of inorganic components, have good biocompatibility and chemical stability, with strong chemical bonding of bone formation, the effect of body fluids, some degradation will occur, free the calcium and phosphorus, was absorbed and used human tissue, resulting in bone conduction, thus causing the material workers and health professionals around the world wide attention. Since the 90s of the 20th century as the rapid development of nanotechnology, many of the application of nano-materials become more widely. Research shows that hydroxyapatite as a surface effect, small size effect and quantum effects and other unique properties, it shows unlimited potential applications. This thesis is based on nano-hydroxyapatite carrier material for the preparation of sustained release drug preparation, choice of model drug was theophylline.First, the experimental use of sol-gel hydroxyapatite monomer, and by scanning electron microscopy, Fourier transform infrared spectroscopy and X-ray diffraction analysis were used to characterize the monomer, the results show that the appearance of the HAP porous structure, the diameter of about 100nm, from the infrared absorption spectrum and X-ray diffraction analysis of view, synthetic hydroxyapatite features were obvious absorption peak position, it can be prepared using a sol-gel method than pure hydroxyapatite nanoparticles.Then, for the hydroxyapatite - compound aminophylline before the prescription inspection, including the physical and chemical properties of aminophylline in vitro testing methods and the main interaction between the drug and excipients and other aspects, the results show that the ammonia tea in various aqueous alkali solubility of the medium are good, and the establishment of theophylline in different media in the standard curve, the final determination by ultraviolet spectrophotometry to determine the content of aminophylline; The experiment also with different molar ratio of hydroxyapatite and aminophylline solution soak for 10 days, and aminophylline and the synthesis of materials at high temperatures, high humidity and light conditions placed on 10 days, to examine the interaction between them , Infrared spectroscopy showed that, HAP, and the characteristic absorption peak of aminophylline the relative intensity of the fluctuations to some extent, but the absorption peak position and shape has not changed, indicating that the same amount in the case of aminophylline, with the the increasing proportion of hydroxyapatite, to absorb the amount of aminophylline reduced, so the relative intensity of the absorption peak decreased, the above results show that both aminophylline and no interaction between the various raw materials can be used to prepare HAP-aminophylline nanocomposite.In addition, this first time successfully prepared in situ synthesis nano-HAP-theophylline complex, and can reach at least 12 hours of sustained-release effect. Test were used to assay and in situ synthesis of hydroxyapatite prepared - aminophylline nanocomposite, and the cumulative in vitro release rate and drug content optimum conditions for the index and found that the adsorption of three batches of samples prepared The average drug loading 35.30mg / g, while the in situ synthesis of composite materials prepared by the average drug loading of 52.33mg / g, And by two different ways of HAP-theophylline complex accumulated in 12h, in vitro release rate reached 80%, but compared with the in situ synthesis, adsorption complexes prepared by the cumulative release rate in the 2h, 50 % of some degree of burst effect. It can be seen, in situ prepared complexes not only the drug is greatly increased, but also to avoid the burst effect, the finalization of this study prepared by HAP-situ nanocomposite aminophylline.In determining the optimal formulation and process conditions after the HAP-aminophylline on the release mechanism of nano-composite conducted a preliminary study confirmed that the drug release from the law of hydroxyapatite as follows: First, the drug adsorbed on the HAP surface first release, with the gradual degradation of hydroxyapatite itself, the internal diameter of the drugs gradually released, after different periods of the complex release kinetics curves is that the early release (0-8h) found a release kinetics, while the latter (10-48h) near zero order release process. From calcium hydroxyapatite single release point of view, synthesis temperature and pH value on the impact of hydroxyapatite crystallinity greater, with the temperature, the crystallinity increased gradually, culminating in hydroxyapatite degradation slowed down, according to the above results can be summed up by changing the experimental conditions control the particle size and crystallinity of HAP within a certain range, then control the degradation process of HAP, thus achieving the goal we need the nature of the controlled release carrier materials, This also needs further experimental study.Then, prepared by in situ synthesis of nano-HAP-aminophylline compound powder, and enteric-coated capsule shell into prepared three batches of HAP-aminophylline slow-release formulations. Test first establishment of HAP-theophylline sustained release capsules of UV detection, and then the appearance of the preparation, load difference, loss on drying, assay and dissolution were investigated, results showed that the preparations by ultraviolet spectrophotometry of ammonia theophylline levels is feasible; by three batches of HAP-theophylline sustained release capsules of quality testing, we established a HAP-theophylline sustained release capsules of quality standards.Finally, HAP-aminophylline on the stability of sustained-release capsules were studied, including accelerated testing and long-term stability test. Accelerated tests which were taken three batches (090901,090902,090903) hydroxyapatite - aminophylline slow-release capsules in 40℃±2℃, RH (relative humidity) 75%±5% under the conditions of place, respectively, 0, 1,2,3,6-month random sampling to detect the target. Long-term stability of the experiment were collected 3 award (090901,090902,090903) hydroxyapatite - aminophylline slow-release capsules in 25℃±2℃, RH 60%±10% under the conditions of placement, respectively, 0,3,6 , 9,12 months of random sampling to detect the target. The results show that the accelerated tests and long-term experiment 3 batches of hydroxyapatite - aminophylline slow-release capsule characters, content and dry weight loss of no change, within the prescribed limits, long-term tests are still ongoing.In conclusion, this study of nano hydroxyapatite as a carrier for the model drug theophylline was investigated sustained-release preparation of synthesis of complex, slow-release mechanism and the sustained release preparation of quality standards and stability, the results show that in situ synthesis can be successfully prepared HAP-drug delivery formulations, demonstrates the use of hydroxyapatite as a release carrier material is feasible, it is also established for the preparation of a new sustained-release preparation of the new platform, the project is very broad application prospects.