Purpose: Fabrication of microparticles relies on the properties of the dispersed phase, the continuous phase, and the method of manufacture, single or double emulsion, speed of mixing, and addition of components. The viscosity of the continuous phase influences the microparticle size and morphology. Poly(vinyl alcohol) (PVA) is widely used as an emulsifier in the continuous phase, however it is available in a number of molecular weights (MW), which may also impact the microparticle characteristics. The purpose of this work was to study the effect of concentration, viscosity, and molecular weight of the continuous phase using low MW (LMW) and high MW (HMW) PVA on the size and morphology of poly(lactic-co-glycolic acid) (PLGA) microparticles.
Methods: The viscosity of LMW PVA solutions at three different concentrations were measured using a rheometer. HMW PVA solutions were then matched to the resulting viscosities, as well as matched to the concentrations. Microparticles were synthesized using a solvent evaporation single emulsion (o/w) method. Briefly, PLGA (MW=34kDa) was dissolved in 3ml of dichloromethane, injected into 100ml of an aqueous PVA solution, the continuous phase, and stirred with an impellor at 1500rpm for 5 minutes. The solution was then allowed to stir for at least 3 hours for microparticle hardening and evaporation of the dichloromethane. The resulting microparticles were collected by filtration and dried overnight.
Results: LMW PVA (MW=13-23kDA) resulted in spherical microparticles with a porous appearance at all concentrations. HMW PVA (MW=30-70kDa) overall resulted in microparticles with a less porous appearance (Figure 1). When HMW PVA was matched to the viscosity of the lowest concentration of LMW PVA, the microparticles appeared much less spherical. Matched concentrations of HMW PVA and LMW PVA, resulted in larger microparticles (20.3/20.0/15.7 m vs 10.3/15.0/14.0 m average diameter), with PDI values <1 (Table 1).
Conclusion: Viscosity is tied to the concentration and molecular weight of the polymer solution, and, in general, increases with an increase in concentration. By selecting a concentration which results in similar viscosities between continuous phases formulated with PVA of different MW, the effect of MW may be studied. Here, it is shown that concentration and molecular weight may have a greater impact than viscosity on properties such as morphology and size. The lowest concentration of the HMW PVA resulted in microparticles that were not spherical, most likely as a result of less overall PVA molecules to stabilize the emulsion. When using PVA as an emulsifier, it is important to select a molecular weight and concentration to achieve the desired final microparticle characteristics.
Pardeep Gupta– Scientific Advisor, Hyalo Technologies, Pennsylvania