Modified release drug products for veterinary use based on in situ biocompatible polymeric matrixes

BERMUDEZ JOSE

Bologna, Italia

Conferencia; I SEMINARI DI SCIENZE FARMACEUTICHE. DIPARTIMENTO DI SCIENZE FARMACEUTICHE. ALMA MATER STUDIORUM - UNIVERSITÀ DI BOLOGNA; 2010

Research activities accomplished during the scholarship generate fundamental and technological knowledge for the design of liquid formulations that once injected and in physiological temperature, form in-situ biocompatible polymer matrices solid or gelatinous, useful for applications in the field of veterinary medicine. The performed studies included experimental activities in order to evaluate the properties of pharmaceutical relevance of new injectable thermosensitive systems formed by the combination of poloxamer 407 (28% w/v) and poloxamer 188 (10-15% w v) with natural macromolecules (carrageenan, sodium hyaluronate, alginic acid and chitosan) in concentrations in the range of 0.05-1.5% w/v. Progesterone was used as a drug model to evaluate the drug release profiles from gels. The viscosity of the formulations directly determines the ease of application. The viscosity values obtained were low, allowing the application with standard syringe and needle. While smaller diameter needle, greater tolerance and acceptance of the treated animal The viscosities of formulations were optimized in a limited range by varying the proportions of poloxamer 188 and macromolecules used in each formulation. The optimization resulted in a delicate compromise; in general, higher viscosity increased efficiency of entrapment of the drug, but lesser facility of injection. It was also observed a significant decrease in gelation temperature with increasing viscosity The obtained results were promising; it was possible to develop product and process engineering for the development of injectable fluid formulations characterized by gelation temperature suitable for depot injectable administration (25-30 °C). Erosion studies were conducted to evaluate the influence of the concentrations of poloxamer and macromolecules in drug delivery platforms. Based on the obtained results, the erosion is considerably influenced by the concentration of poloxamer 188 and macromolecules. The erosion of the hydrogels decreases significantly with a small increase in the concentration of poloxamer 188 and the corresponding macromolecules. Macromolecules apparently reinforce the structure of the hydrogel, causing a decrease in the erosion of the polymeric platforms. Studies of progesterone release from thermosensitive gels were performed to evaluate the feasibility of these systems as platforms for controlled release drug. The results showed that the higher concentration of the macromolecule in the formulation decreases the release of progesterone, because of that it could be establish a correlation between the processes of erosion and drug release from hydrogels. According to the kinetic model used to evaluate the data release, in addition with diffusion mechanism, the erosion of the gels is involved in the kinetic control of drug release from thermosensitive gels. Besides, also it was determined on the basis of the gel strength tests, that this property is correlated with the erosion and release properties mentioned above. In conclusion, these studies demonstrated that the addition of macromolecules into poloxamers blends can be considered a useful tool to design thermosensitive injectable depot systems, if added in suitable amounts. Finally, the low viscosity of poloxamers systems at low temperature makes them might be easily injected intramuscularly into the animal body via a syringe, and used in warm climates due to the reversibility of gelation process. These encouraging results, that need to be further assessed by in vivo experiments, evidence the possibility of using these novel platforms as injectable depot systems for veterinary use.