Evaluation of drug loading andrelease from hollow calciumphosphate microspheres

Introduction: Bioceramics are widely used in health care, ceramics are used in various parts of the body. Calcium phosphate is a bioceramic material that has been used in dentistry and medicine for a long time, for example: orthopedic load-bearing applications, coating for chemical bonding, dental implants, temporary bone space fillers, orthopedic fixation device and spinal surgery. Since the use of biomaterials and bioceramics has increased not only for repairing and replacement of damaged parts in the body but also as a new drug delivery system, different morphology of the ceramics has been studied. Drug delivery is of great interest in pharmaceutical science. Aim: The aim of this study was to evaluate the loading and release of drug from ceramic microspheres. In this study hollow calcium phosphate spheres were of interest. Methods: The method used in this thesis was the soaking method where spheres were soaked in drug solution, analysis of drug concentration before and after soaking was used to determine drug loading. Another method was loading during preparation of spheres. Characterisation of the spheres and drugs was performed using BET, X-ray diffraction and SEM. Drug release was carried out using a UPS dissolution bath. Drug release models that were evaluated in this thesis were Peppes, Higuchi and first order kinetics. Model drugs were zolidem and sodium salicylate Results: Results showed that only zolpidem was loaded onto the spheres, different amount of drug was absorbed depending on loading time and concentration. The results also showed that no drug loading occurred when trying to load during sphere preparation. Crystallization of drug particles shaped as needles/fibers also occurred. BET showed a decrease in surface area when loading compared to non loaded spheres and a decrease in pore size volume. Drug release showed a slower release when drugs were in a complex with spheres, the drug release seemed to fit the Higuchi model the best and could indicate a diffusion mechanism. Discussion: Different amount of drug loading was expected for the different concentration and loading time, the lack of loading of sodium salicylate was however not expected. Crystallization of drug was also not expected but could be assumed to occur due to high surface tension in the sphere/drug solution. Decrease in surface area after loading could be due to the mixture of spheres and drug fibers, the spheres/fibers could be analyzed as one large unit and result in smaller surface area. One reason for the decrease in pore size volume that could not be excluded is that if drug is absorbed into the sphere pores this could result in a decrease in pore size volume. Conclusion: The study showed that the hollow calcium phosphate spheres can be loaded with drug, in this case zolpidem, but drug crystallization on the surface of the spheres could occur. Loading during sphere preparation was not successful in this thesis. It was also found that the drug and the spheres content could react with each other. Release of the drug from the spheres showed that the spheres/drug complex could affect the release of drug by making the release slower, release seems to fit a diffusion mechanism.