Microparticles produced by the hydrogel template method for sustained drug delivery

Abstract

Polymeric microparticles have been used widely for sustained drug delivery. Current methods of microparticle production can be improved by making homogeneous particles in size and shape, increasing the drug loading, and controlling the initial burst release. In the current study, the hydrogel template method was used to produce homogeneous poly(lactide-co-glycolide) (PLGA) microparticles and to examine formulation and process-related parameters. Poly(vinyl alcohol) (PVA) was used to make hydrogel templates. The parameters examined include PVA molecular weight, type of PLGA (as characterized by lactide content, inherent viscosity), polymer concentration, drug concentration and composition of solvent system. Three model compounds studied were risperidone, methylprednisolone acetate and paclitaxel. The ability of the hydrogel template method to produce microparticles with good conformity to template was dependent on molecular weight of PVA and viscosity of the PLGA solution. Drug loading and encapsulation efficiency were found to be influenced by PLGA lactide content, polymer concentration and composition of the solvent system. The drug loading and encapsulation efficiency were 28.7% and 82% for risperidone, 31.5% and 90% for methylprednisolone acetate, and 32.2% and 92% for paclitaxel, respectively. For all three drugs, release was sustained for weeks, and the in vitro release profile of risperidone was comparable to that of microparticles prepared using the conventional emulsion method. The hydrogel template method provides a new approach of manipulating microparticles.

Keywords: Controlled release; Methylprednisolone acetate; PLGA microparticle; PVA template method; Paclitaxel; Risperidone.

Figure 1

Scanning electron microscope images of microparticles prepared using 87~89% hydrolyzed PVA templates of various average molecular weights: (A) 13,000~23,000 Da; (B) 31,000~50,000 Da; and (C) 146,000~186,000 Da.

Figure 2

Scanning electron microscope images of RIS-containing microparticles prepared using 12.5% PLGA with intrinsic viscosity of 0.95~1.20 dL/g (A), PLGA-RIS (12.5%–12.5%) solution (B), and PLGA-RIS (6.2%–7.0%) solution (C).

Figure 3

Fluorescent (A and B) and scanning electron microscope (C and D) images of microparticles prior to (A) dissolving PVA templates and after collecting and drying (B–D).

Figure 4

SEM image showing large pores formed on the surface of microparticles prepared by using a co-solvent containing DCM.

Figure 5

X-ray diffractograms comparing pure drug and encapsulated form of RIS (A), MPA (B), and PTX (C).

Figure 6

Comparison of drug loading trends for RIS formulations A) effect of PLGA type based on L:G ratio; B) effect of PLGA concentration; C) effect of drug concentration; D) effect of solvent ratio. *: p<0.05; **: p<0.001

Figure 7

Comparison of drug loading and encapsulation efficiency of model compounds. MPA microparticles were prepared from BA and DCM solvent mix (v/v=50:50) due to low solubility in EA

Figure 8

Comparison of RIS drug release from formulation in phosphate buffer (pH 7.4, 37 °C) A) comparison by PLGA type (L:G); B) comparison by different solvent combinations

Figure 9

Comparison of release profiles of RIS, MPA and PTX from 8515 PLGA microparticles.

Figure 10

Comparison of release profiles of RIS-loaded microparticles prepared using hydrogel template and emulsion methods