The purpose of this study was to compare the effect of polymer foam morphology and density prior to compaction on the kinetics of isoniazid (INH) release from the final highdensity extruded matrices. The feasibility of preparing low density foams of several biopolymers, including poly(Llactide) (PLLA), poly(glycolide) (PGA), poly(DL-lactide-coglycolide) (PLGA), poly(␥-benzyl-L-glutamate) (PBLG), and poly(propylene fumarate) (PPF), via a lyophilization technique was investigated. Low-density foams of PLGA, PBLG, and a mixture of PLGA and PPF were successfully fabricated by lyophilization of the frozen polymer solutions either in glacial acetic acid or in benzene. The morphology of these foams depends on the polymer as well as the solvent used in the fabrication process. Thus, PLGA produces a capillary structure when lyophilized from benzene solution and a leaflet structure from glacial acetic acid, but PBLG yields a leaflet structure from benzene. Matrices were prepared by impregnating these foams with aqueous solutions of INH, removing the water by a second lyophilization, and then compressing the low-density INH containing foams by compaction and high-pressure extrusion. The resulting nonporous matrices had densities of approximately 1.30 g/cm 3 . In vitro kinetics were in accord with the Roseman-Higuchi diffusion model and demonstrate that release rates depend on the initial foam density, while foam structure has little influence on the release kinetics.
Poly(D,L-lactic-co-glycolic) acid (PLGA) microspheres containing plasmid DNA encoding the firefly luciferase gene were prepared using the water-in-oil-in-water (w/o/w) double emulsion and solvent evaporation method. In this study, we investigated the effects of three process parameters on DNA microencapsulation: (1) emulsification method used to generate the primary emulsion, (2) water/oil ratio during formation of the first emulsion, and (3) surfactant concentration used in the preparation of the second emulsion. The resulting formulations were also analyzed for microsphere size, encapsulation efficiency, and kinetics of DNA release. We found that although each process alteration resulted in encapsulation of biologically active, structurally intact DNA, the surfactant and water/oil ratio significantly affected the size, release kinetics and encapsulation efficiency of plasmid DNA.
The release mechanisms of a small molecular drug from biodegradable poly(d,l-lactide-co-glycolide) (PLGA) cylindrical matrices were investigated. Isoniazid (INH), one of the most effective drugs against tuberculosis (TB), was selected as the model drug. Controlled-release matrices consisting of the drug and polymer were fabricated by two methods. The first of these, the dry-mixing method, involved the extrusion of a mixture of micronized drug and polymer particles as rods. In the second technique, the low density polymeric foam method, drug particles were enclosed in the cells of porous polymeric foams prior to extrusion. In vitro, the dry-mixed matrices released INH more rapidly than the polymeric foam matrices. The Roseman-Higuchi diffusion model, which had previously been found to be effective in analyzing the release kinetics of INH from the dry-mixed matrices, also fit the kinetics of INH released from matrices prepared from polymeric foams. This indicated that the release was still diffusion-controlled rather than degradation-controlled. The release mechanisms were further investigated, and two diffusion mechanisms, pore diffusion and lattice diffusion, were proposed for the INH controlled-release matrices according to the way in which they were prepared. Matrices prepared by the dry-mixing method appear to segregate drug particles along polymer grain boundaries and thus have a pore diffusion mechanism, while matrices prepared by the foam method entrap drug within the porous structure of foams and thus display a lattice diffusion mechanism. Theoretically, these two diffusion mechanisms can be identified by their activation energies for diffusion. With varying in vitro temperature, the activation energies were calculated from plots of ln (DIT) vs T-1 and in D vs T-1, where D is the diffusivity and T is the in vitro temperature in K. According to the results, we concluded that the INH from the dry-mixed matrices diffused through the drug channels filled with the medium, while the INH from the foam matrices diffused through the polymer lattice.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.