Polylactic acid

The rate of release of thioridazine from polylactide microcapsules, prepared by solvent evaporation from oil in water emulsions, was enhanced by the use of a base, NaOH. The rate of drug release depended upon the amount of base added to the aqueous phase of the emulsion. Using the results from scanning electron microscopy, it was suggested that the drug release could be due to modification of the internal structure of the microspheres during their preparation (Fong et al., 1987).

Bodmeier and McGinity (1987c) encapsulated quinidine and quinidine sulfate with poly(DL-lactic acid) by the solvent evaporation method. The drug and the polymer were dissolved with heat in methylene chloride and this solution was then emulsified into the aqueous phase containing polysor-bate 80 and at the pH of minimum drug solubility to minimize drug loss to the aqueous phase. Stirring was continuous until the organic solvent evaporated. The product was then filtered, washed with water and dried.

In a second paper dealing with quinidine and poly(DL-lactic-acid), Bodmeier and McGinity (1987b) showed that the drug loss to the aqueous phase occurred within the first 1-2 min of the emulsification step, as the pH was changed from 7 to 12 or 12 to 7. They suggested that the ability to change the pH without influence to the actual drug content within the microcapsule may permit the preparation of microcapsules at extended pH values. An increase in the volume of the aqueous phase resulted in an increase of drug content in the microcapsules. This was attributed to faster precipitation of the polymer at the droplet interface, as a result of polymer solvent diffusing into the water. An increase of temperature from 0 to 35°C during the formation of the microcapsules caused a decrease in the quinidine content of the product. This was attributed to an increase in the solubility of the drug in the aqueous phase. The higher temperature also caused an increase in the vapour pressure of the polymer solvent, leading to an increasing flow across the interface, resulting in film fracture.

In a subsequent paper, Bodmeier and McGinity (1988) reported on solvent selection for the preparation of microspheres by the evaporation method using poly(DL-lactide). The successful encapsulation of the drug within the microsphere was associated with: (a) a fast rate of precipitation of the polymer from the organic phase; (b) a low water solubility of the drug in the aqueous phase; and (c) a high concentration of the polymer in the organic phase. It was found that the rate of polymer precipitation was strongly influenced by the rate of diffusion of the organic solvent into the water phase. Organic solvents with low water solubility resulted in a slow polymer precipitation, permitting the drug to partition fully into the aqueous phase. Water-miscible organic solvents, when added to the organic phase, improved the drug content in the microspheres. The preparation of a solubility envelope for the polymer and an envelope for microsphere formation based on three-dimensional solubility parameters was useful for the selection of suitable solvent mixtures and the interpretation of solvent, nonsolvent, polymer interactions and the formation of the microspheres.

Spores and viable cells were encapsulated with poly(lactic acid) dissolved in dichloromethane. Either spores or nutrient broth containing viable cells were added to the polymer solution. Then this suspension was added to a methylcellulose solution and the mixture stirred until the solvent evaporated. After filtration the product was washed with water and air dried. The core material was also encapsulated with gelatin and acacia using the complex coacervation method. The microcapsules produced were larger using the solvent evaporation method. Both methods permitted the encapsulated material to retain some viability. The solvent evaporation method was simple and more reproducible (Pepeljnjak, 1988).

In a series of papers Jalil and Nixon (1989) investigated the preparation and properties of microcapsules using poly(L-lactic acid) or poly(DL-lactic acid). In the first paper the phenobarbitone was microencapsulated by dissolving the polymer, poly(L-lactic acid), and drug in dichloromethane and dispersing the solution in 1 % aqueous gelatin solution, to give an o/w system. With subsequent evaporation, the drug was found to be poorly encapsulated and microcapsules were small. In the other method of preparation, w/o, a solution of drug and the polymer in acetonitrile dispersed in light liquid paraffin containing Span 40 was allowed to evaporate. Drug loading in this system was high and the large microcapsules had a more porous surface.

In their next paper, Jalil and Nixon (1990b) used the poly(DL-lactic acid), acetonitrile, light liquid paraffin system for preparing phenobarbitone microcapsules. With an increase in temperature for evaporation, the surface of the microcapsules became more irregular and porous owing to deposition of phenobarbitone near the surface of the microcapsules. As the polymer concentration was increased, the surface became more irregular and non-continuous owing to rapid precipitation of the polymer, and the microcapsules became larger. The encapsulation efficiency was not appreciably affected by changes in temperature of preparation and polymer con centration. When the initial core loading was decreased the encapsulated efficiency decreased.

Jalil and Nixon (1990c), again using poly(DL-lactic acid), found that as polymers with lower molecular weights were used the microcapsule size decreased and the rate of swelling in an aqueous environment was greater. The gross morphology, encapsulation efficiency and density were not affected by changes in the molecular weight. In subsequent papers Jalil and Nixon (1990d,e) investigated the effect of polymer molecular weight on release kinetics and storage on microcapsule characteristics.

Gentamycin sulfate was encapsulated with poly(L-lactic acid) by adding the drug to a solution of the polymer in methylene chloride (Sampath et al., 1992). Coacervation was induced by adding hexane at a controlled rate. Hardening was achieved by stirring for 2h and the product was washed with hexane and allowed to dry. After sieving, the 125-450 ¡im fraction was used for further studies. A volume-based size distribution indicated a mean diameter of 343 /tm, and a mean diameter of 14.8 ¡im was obtained based on particle number. This discrepancy was explained in terms of the breakup of aggregates. Dissolution studies at pH 7.6 showed that microcapsules with higher drug loading released their contents faster, and complete release ranged from 3 days to 3 weeks. Cylindrical implants were prepared by compressing the microcapsules in a punch and die and several dissolution studies were made on these products.

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