Effect of Basic Factors of Preparation on Characteristics, Hydrolytic Degradation, and Drug Release From Poly(ester-anhydride) Microspheres

Abstract

Functional poly(ester-anhydride) microspheres were prepared using emulsion solvent evaporation (ESE) and phase inversion methods (PIM). The poly(ester-anhydride)s were obtained by polycondensation of sebacic acid (SBA) and oligo(3-allyloxy-1,2-propylene succinate) terminated with carboxyl groups (OSAGE). The effects of various parameters, including: polymer and emulsifier concentrations, stirring speed and molecular weight of polyvinyl alcohol (PVA) used as emulsifier on size, size distribution and morphology of microspheres obtained by ESE technique were examined. The size of microspheres obtained was in the range 2–30 µm and depended mainly on the stirring rate in emulsion formulation process, as well as concentration of polymer solution used. Molecular weight of PVA, and its concentration in aqueous phase, significantly influenced tendency to agglomeration of microparticles formed, but only slightly changed the size of microspheres. The present study demonstrated that the ESE method can be useful to formulate, from functional poly(ester-anhydride)s, small (2–3 µm) or large (20–30 µm) microspheres with relatively narrow size distribution. Such microspheres were loaded with three model compounds (rhodamine B, p-nitroaniline, and piroxicam) with different water solubility and their release characteristics were examined. In the present study microparticles were also obtained by alternative phase inversion method to compare mainly stability of polymers during formulation of microspheres by both techniques.

Keywords:

• Biodegradable microspheres
• emulsion solvent evaporation
• microencapsulation
• phase inversion
• poly(ester-anhydride)

Acknowledgment

The author thanks the Polish State Committee for Scientific Research for financial support by grant no. N205 016534. The author reports no conflicts of interest. The author alone is responsible for the content and writing of this article.

Notes

^a PVA 88% hydrolyzed MW = 88000 g/mol, speed of homogenizer = 9000 rpm.

^a D_n = ca. 30 µm.

^b D_n = 2–3 µm.