INCAPSULAZIONE DI PRINCIPI ATTIVI IN MICROPARTICELLE LIPIDICHE PER SOMMINISTRAZIONE TOPICA ED INALATORIA

The aim of my project is the production of solvent‐free carriers for drug delivery based on lipid microparticles. In particular, the encapsulation of sunscreen agents for topical administration and the entrapment of cortisteroids for inhalation therapy in solid lipidic microparticles (SLMs) were investigated. These carriers were prepared by melt techniques and spraycongealing methods. An essential requirement for the efficacy and safety of sunscreen agents is a high photostability, since the light‐induced degradation of the UV filter not only decreases the expected protective power but can also lead to the accumulation on the skin of harmful photolytic products. Recent investigations have shown that in rat as well as in man, the UV‐B (290‐ 320nm) filter methylbenzylidene camphor (4‐MBC) is systemically adsorbed after topical application. This aspect should be considered with attention, since in‐vitro animal studies have reported on the estrogenic activity of 4‐ MBC. Therefore, there is a need for new systems able to minimize the skin penetration of 4‐MBC. The results obtained demonstrated that encapsulation of 4‐MBC in lipidic microparticles, after their introduction in a model cream, decreases the percutanous penetration of the sunscreen, thereby minimising its systemic uptake and the potentially associated toxicological risks. The data reported also showed that although the in vitro test represents a simple model for percutaneous penetration studies, in‐vivo investigations are necessary for more realistic assessment of the factors affecting the degree of skin adsorption. Moreover, published reports have demonstrated that butyl methoxydibenzoylmethane (BMDBM), the most efficient and widely used UV‐A filter, is not sufficiently photostable decomposing and generating free radical when illuminated with simulated sun‐light. In order to reduce the sunscreen photodegradation, the incorporation of BMDBM into solid lipid microparticles together with photostabilizers (i.e. 4‐methylbenzylidene camphor and octocrylene) was investigated. From the results obtained the SLMs containing BMDBM together with the photostabilizer were more effective in enhancing the UV‐A filter photostability than SLMs loaded with BMDBM alone. Moreover, lipid microparticles loaded with BMDBM alone were prepared to evaluated the UV filter skin permeation in vivo, by the tape stripping method. Studies were also undertaken to develop SLMs loaded with high amounts of BMDBM. The microparticles were produced by the classical melt dispersion method and the spray congealing technique with pneumatic atomizer. However, release studies indicated that spray congealing enabled a more efficient modulation of BMDBM release from the SLMs. Moreover, the SLMs produced by spray congealing achieved a more marked reduction in BMDBM photodecomposition. Therefore, the spray congealing technique was found to achieve rapid and solvent free production of SLMs with a high BMDBM loading capacity. For the inhalation therapy, the aim of project was to find optimal conditions for the production of SLMs containing Budesonide for drug‐targeting to the lung, The study involved the charaterization in terms of morphology (shape, surface and roughness) and size of the SLMs produced, determination of the controlled release by flow through apparatus in different media and finally evaluation of the regional lung deposition of particles by MSLI (Multi‐stage liquid impinger). The study has shown that solid lipid microparticles may provide a useful approach to controlled release respiratory therapy.