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Date of Award


Document Type

Dissertation - Pacific Access Restricted

Degree Name

Doctor of Philosophy (Ph.D.)




In view of current interest in several oligopeptide drugs currently being investigated for controlled implantable delivery, glycine, diglycine, triglycine, tetraglycine and pentaglycine were chosen as model compounds for encapsulation in biodegradable microspheres of DL-polylactide (DL-PLA) by a technique based on oil-in-oil emulsion and the solvent evaporation principle. A DL-polylactide concentration of 10.3% w/w and emulsifier (sorbitan sesquioleate) concentration of 0.3% v/v produced good yields of microspheres with excellent entrapment when processed under following conditions: emulsion time, 1 min; solvent evaporation time, 2 min; internal phase-external phase ratio, 1:7; stirring speed, 1100 rpm; emulsion temperature, 5$\sp\circ$C; and maximum processing temperature, 35$\sp\circ$C. Microspheres prepared as above at four different loadings (2.5, 5.0, 7.5, and 10.0% w/w) were analyzed for morphological and in vitro release characteristics. Analysis of the release data and scanning electron photographs suggested that the release of glycine and its homopeptides from DL-PLA microspheres was most likely by diffusion through the matrix. However, for models having low aqueous solubility, e.g., tetra- and pentaglycine, dissolution played a rate-limiting role. Microspheres of glycine prepared with DL-PLA plasticized with 10% triacetin demonstrated the slowest release, with the first 50% entrapped glycine released over four days and next 25% released at a constant rate over 17 days. This was in sharp contrast to unplasticized microspheres from which glycine was completely leached out in 24 h. Interestingly, while the plasticizer decreased the rate of release of glycine, it appeared to promote the degradation of the polymer DL-PLA.



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