Investigation on structural integrity of PLGA during ammonolysis-based microencapsulation process

The objective of this study was to gain insights into the structural integrity of PLGA during an ammonolysis-based microencapsulation process. PLGA (lactide:glycolide ratio = 75:25; Mw = 25,925 g/mol) was dissolved in ethyl acetate or isopropyl formate (3–6 ml), which was emulsified in an aqueous phase. Ammonia, being added to the emulsions, reacted with the dispersed solvents to yield water-miscible solvents. Consequently, emulsion droplets were solidified into microspheres. To evaluate the impact of ammonia upon PLGA, the molar ratio of ammonia to a dispersed solvent varied from 1 to 2 and 3. After preparation of microspheres by the ammonolysis-based procedure, the lactide:glycolide composition and Mw of PLGA were analyzed by 1H NMR and GPC. Our results demonstrated that ammonia did indeed catalyze the cleavage of PLGA ester bonds during microencapsulation. Strikingly, PLGA degradation was affected by solvent type and volume, as well as ammonia concentration. For instance, when 6 ml of ethyl acetate was used and the molar ratio of ammonia to the solvent was 3, the glycolide content and Mw of the microspheres considerably decreased to 17.56% and 10,814 g/mol, respectively. There were little changes in these terms, however, when microspheres were prepared using 3 ml of isopropyl formate and an equimolar amount of ammonia. Depending upon microencapsulation conditions, progesterone encapsulation efficiency ranged from 71.6 to 98.8%. Also, its release behavior was significantly influenced by ammonolysis-related process parameters. Our study demonstrated that all these contrasting results arose from differences in solvent reactivity toward ammonolysis, the rate of microsphere solidification, and the availability of ammonia to PLGA ester linkages.

Reductions in PLGA molecular weight caused by (A) ethyl acetate- and (B) isopropyl formate-based ammonolysis microencapsulation processes. Solvent type and volume, as well as the molar ratio of ammonia to solvent, are critical parameters that influence the degree of molecular weight reduction of PLGA.Figure optionsDownload as PowerPoint slide