| The bioavailability of eye drops is quite low due to the defence mechanisms of the eye, such as lachrymation, reflex blinking and increased drainage. In the theoretical part of the thesis, a review of the structures responsible for the low bioavailability of ocular drops is given, as well as the routes followed to overcome this problem. Special attention is given to micro- and nanoparticles, as they are the scope of the practical part. The last chapter of the theoretical part contains an introduction to experimental design, a technique to plan and execute experiments in such a way that the influence of a number of parameters on the result of a process can be estimated, performing a minimal amount of experiments.; The main aim of the work presented in this thesis was to investigate the possibility to produce nano-sized particles with biocompatible and biodegradable polymers and to investigate the parameters that determine important particle features such as particle size and zeta potential value, as well as drug loading and drug release.; Two polymers were used to produce nanoparticles: gelatine and PLGA, a copolymer of lactic and glycolic acid. Gelatine particles were produced enclosing hydrophilic (pilocarpine HCl) as well as hydrophobic (hydrocortisone) drugs. An influence of the pH value during particle preparation on the particle size was observed. Slightly negative zeta potential values were measured. In the case of the pilocarpine HCl-loaded spheres, no influence of the gelatine type or the pH level was observed. When hydrocortisone was entrapped, a difference in particle zeta potential value between gelatine type A and gelatine type B particles was observed. A high drug entrapment was established for pilocarpine HCl. Hydrocortisone was complexed with cyclodextrins in order to increase the aqueous solubility. The drug encapsulation was less high than in the case of pilocarpine HCl, but still amounted about 30--40%. A sustained release for both drugs was observed, compared to the aqueous drug solutions. In the case of hydrocortisone, the release data suggested that the release rate depends on the type of cyclodextrin employed.; The synthetic polymer employed for nanoparticle production was poly(lactic-co-glycolic acid) (PLGA). The spheres were prepared using an emulsification solvent evaporation method. In chapter VII, the influence of a number of preparation parameters on the particle properties was investigated. Two of the factors investigated were shown to have an influence on the particle size: the presence of buffer and the concentration of PVA in the outer water phase. The buffer concentration also influences the particle zeta potential value. The only factor, which had a significant effect on the pilocarpine HCl entrapment, was the ratio drug:polymer.; Several biocompatible polymers were tested and compared to PVA as stabilizers in the preparation of PLGA nanoparticles. (Abstract shortened by UMI.)... |
