Physico-chemical analysis of metronidazole encapsulation processes in Eudragit copolymers and their blending with amphiphilic block copolymers.

A physico-chemical analysis of metronidazole-Eudragit copolymers L100 and RLPO (a cationic polymeric matrix with an electrophilic character) was carried out in order to explore the drug-polymer interaction and its possible effects on the encapsulation and release profiles. An oil-in-oil encapsulation procedure was designed to obtain more intimate drug-matrix mixtures and to obtain a better insight into the details of the interaction. The encapsulation efficiency obtained in these cases was high (in the range of 85-95%), but the release rates were quite rapid. Solubility and interaction between metronidazole and copolymers are discussed in detail with a view to explaining the results. Amphiphilic block copolymers of poly(ethylene)-b-(polyethylene oxide) (20, 50 and 80% PEO) were tested as a matrix for metronidazole release in order to improve drug profiles. The performance of RLPO as the matrix for drug release was improved by blending it with amphiphilic block copolymer poly(ethylene)-b-(polyethylene oxide) (20% PEO). The release mechanism of metronidazole is governed mainly by the swelling of RLPO, yielding a better fit with the second-order Schott equation.

Physical chemistry behavior of enteric polymer in drug release systems.

We report an analysis based on the electrical impedance (EI) spectrum of the samples of enteric random copolymer poly-methacrylic acid-co-methyl methacrylate as a function of pH of media. Important aspects of the charge transport and conformational processes in enteric polymer can be identified by mapping the complex impedance as a function of the frequency, which allows that some parallelism between titration and EI measurements can be obtained. However, the latter technique reveals details of this complex equilibrium that not appear using common titration methods. The relaxation frequency observed in the impedance spectrum act as a probe for the detection of phase transitions and conformational changes of the polymeric chains, once the distribution of size of particles can be related with this parameter. The progressive introduction of the alkali and the variation of pH between 4 and 10 are associated with a three steps process, related to the equilibrium shift from a precipitated solid or suspension, to a colloidal-like dispersion and to a complete solubilization of the copolymer. All those experimental features were reflected simultaneously as a turning point in plots of impedance, relaxation frequency and visible absorption with alkali addition giving a better and detailed insight to these processes.

Nano-encapsulation of protein using an enteric polymer as carrier.

In this preliminary work, an enteric polymer has been used for encapsulating bovine serum albumine (BSA) as a model protein drug. Poly (lactide-co- glycolide) has been commonly used for oral administration purposes as a polymer matrix, but in this case an enteric polymer was used effectively to protect the protein in a gastric environment. A modified water/oil/water technique was used to decrease the particle diameter, and transmission electron microscopy experiments showed that the average diameter of the nanoparticles obtained was below 100 nm. The spherical nature of the particles and their diameters strongly depend on the control of the process parameters. The encapsulation efficiency was 77% for sample B4, and protein release profiles for both samples B3 and B4 indicate that these systems possess controlled-release characteristics. Finally, as a result of electrophoresis (SDS-PAGE), the BSA was not chemically affected under encapsulation conditions.