Development of β-cyclodextrin-based hydrogel microparticles for solubility enhancement of rosuvastatin: an in vitro and in vivo evaluation

Abstract

The aim of this study was to enhance the solubility of rosuvastatin (RST) calcium by developing β-cyclodextrin-g-poly(2-acrylamido-2-methylpropane sulfonic acid [AMPS]) hydrogel microparticles through aqueous free-radical polymerization technique. Prepared hydrogel microparticles were characterized for percent entrapment efficiency, solubility studies, Fourier transform infrared spectroscopy, differential scanning calorimetry, thermal gravimetric analysis, powder X-ray diffraction, scanning electron microscopy, zeta size and potential, swelling and release studies. Formulations (HS1-HS9) have shown entrapment efficiency between 83.50%±0.30% and 88.50%±0.25%, and optimum release was offered by formulation HS7 at both pH levels, ie, 1.2 (89%) and 7.4 (92%). The majority of microparticles had a particle size of less than 500 µm and zeta potential of -37 mV. Similarly, optimum solubility, ie, 10.66-fold, was determined at pH 6.8 as compared to pure RST calcium, ie, 7.30-fold. In vivo studies on fabricated hydrogel microparticulate system in comparison to pure drug were carried out, and better results regarding pharmacokinetic parameters were seen in the case of hydrogel microparticles. A potential approach for solubility enhancement of RST calcium and other hydrophobic moieties was successfully developed.

Keywords: hydrogel microparticles; polymerization; rosuvastatin calcium; β-cyclodextrin solubility.

Figure 1

Schematic representation of hydrogel microparticle synthesis. Abbreviations: AMPS, 2-acrylamido-2-methylpropane sulfonic acid; APS, ammonium persulfate; β-CD, β-cyclodextrin; MBA, N,N′-methylene bisacrylamide.

Figure 2

FTIR spectra of (A) RST calcium, (B) β-cyclodextrin, (C) MBA, (D) AMPS, (E) APS, (F) physical mixture of β-CD and RST calcium, (G) physical mixture of RST, APS, AMPS and MBA, (H) hydrogel microparticles. Abbreviations: AMPS, 2-acrylamido-2-methylpropane sulfonic acid; APS, ammonium persulfate; β-CD, β-cyclodextrin; FTIR, Fourier transform infrared; MBA, N,N′-methylene bisacrylamide; RST, rosuvastatin.

Figure 3

DSC (left) and TGA (right) curves of (A) RST calcium, (B) β-CD, (C) hydrogel microparticles. Abbreviations: β-CD, β-cyclodextrin; DSC, differential scanning calorimetry; RST, rosuvastatin; TGA, thermal gravimetric analysis.

Figure 4

Scanning electron micrographs of lyophilized hydrogel microparticles.

Figure 5

PXRD pattern of (A) RST calcium, (B) β-CD, (C) physical mixture and (D) hydrogel microparticles. Abbreviations: β-CD, β-cyclodextrin; PXRD, powder X-ray diffraction; RST, rosuvastatin.

Figure 6

TEM micrograph of lyophilized hydrogel microparticles. Abbreviation: TEM, transmission electron microscopy.

Figure 7

Zeta size and zeta potential. Notes: (A) Zeta size measurement of hydrogel microparticles. (B) Zeta potential measurements of hydrogel microparticles.

Figure 8

In vitro drug release profiles. Notes: (A) Cumulative% drug release from hydrogel microparticles and RST tablets at pH 6.8. (B) Cumulative% drug release from hydrogel microparticles and RST tablets at pH 1.2. Abbreviation: RST, rosuvastatin.

Figure 9

Solubility studies of pure drug and hydrogel microparticles. Abbreviations: AMPS, 2-acrylamido-2-methylpropane sulfonic acid; β-CD, β-cyclodextrin; RST, rosuvastatin.

Figure 10

ES% at pH 1.2 and pH 7.4 (HS7). Abbreviation: ES%, equilibrium swelling percent.

Figure 11

Combined plasma profile of RST calcium after the administration of hydrogel microparticles and commercially available RST tablets. Abbreviation: RST, rosuvastatin.