Effect of Hydrophilic Polymers on Complexation Efficiency of Cyclodextrins in Enhancing Solubility and Release of Diflunisal

Abstract

The effects of three hydrophilic polymers, namely, carboxymethyl cellulose sodium (CMC-Na), polyvinyl alcohol (PVA) and poloxamer-188 (PXM-188) on the solubility and dissolution of diflunisal (DIF) in complexation with β-cyclodextrin (βCD) or hydroxypropyl β-cyclodextrin (HPβCD), were investigated. The kneading method was used at different drug to cyclodextrin weight ratios. Increases in solubility and drug release were observed with the DIF/βCD and DIF/HPβCD complexes. The addition of hydrophilic polymers at 2.5, 5.0 and 10.0% w/w markedly improved the complexation and solubilizing efficiency of βCD and HPβCD. Fourier-transform infrared (FTIR) showed that DIF was successfully included into the cyclodextrin cavity. Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) confirmed stronger drug amorphization and entrapment in the molecular cage of cyclodextrins. The addition of PVA, CMC-Na or PXM-188 reduced further the intensity of the DIF endothermic peak. Most of the sharp and intense peaks of DIF disappeared with the addition of hydrophilic polymers. In conclusion, PXM-188 at a weight ratio of 10.0% w/w was the best candidate in enhancing the solubility, stability and release of DIF.

Keywords: complexation; diflunisal; dissolution rate; hydrophilic polymers; hydroxypropyl β-cyclodextrin; β-cyclodextrin.

Figure 1

Phase solubility diagram of DIF in aqueous solution of βCD with/without PVA (a); with/without PXM-188 (b); Phase solubility diagram of DIF in aqueous solution of HPβCD with/without PVA (c); with/without PXM-188 (d). Mean ± SD, N = 3.

Figure 1

Phase solubility diagram of DIF in aqueous solution of βCD with/without PVA (a); with/without PXM-188 (b); Phase solubility diagram of DIF in aqueous solution of HPβCD with/without PVA (c); with/without PXM-188 (d). Mean ± SD, N = 3.

Figure 2

Mean dissolution profiles of DIF, binary and ternary systems with βCD (a) and HPβCD (b). Mean ± SD, N = 3.

Figure 2

Mean dissolution profiles of DIF, binary and ternary systems with βCD (a) and HPβCD (b). Mean ± SD, N = 3.

Figure 3

Scanning electron photomicrographs of (a) DIF; (b) βCD; (c) DIF/βCD (1:2); (d) HPβCD; (e) DIF/HPβCD (1:2); (f) PVA; (g) CMC-Na; (h) PXM-188; (i) DIF/βCD (1:2) PVA 10%; (j) DIF/βCD (1:2) CMC-Na 10%; (k) DIF/βCD (1:2) PXM-188 10%; (l) DIF/HPβCD (1:2) PVA 10%; (m) DIF/HPβCD (1:2) CMC-Na 10%; (n) DIF/HPβCD (1:2) PXM-188 10%.

Figure 4

FTIR spectra of (a) DIF; (b) βCD; (c) HPβCD; (d) PVA; (e) CMC-Na; (f) PXM-188; (g) DIF/βCD (1:2); (h) DIF/HPβCD (1:2); (i) DIF/βCD (1:2) PVA 10%; (j) DIF/βCD (1:2) CMC-Na 10%; (k) DIF/βCD (1:2) PXM-188 10%; (l) DIF/HPβCD (1:2) PVA 10%; (m) DIF/HPβCD (1:2) CMC-Na 10%; (n) DIF/HPβCD (1:2) PXM-188 10%.

Figure 5

DSC thermograms of (a) DIF; (b) βCD; (c) HPβCD; (d) PVA; (e) CMC-Na; (f) PXM-188; (g) DIF/βCD (1:2); (h) DIF/HPβCD (1:2); (i) DIF/βCD (1:2) PVA 10%; (j) DIF/βCD (1:2) CMC-Na 10%; (k) DIF/βCD (1:2) PXM-188 10%; (l) DIF/HPβCD (1:2) PVA 10%; (m) DIF/HPβCD (1:2) CMC-Na 10%; (n) DIF/HPβCD (1:2) PXM-188 10%.

Figure 6

XRD diffractograms of (a) DIF; (b) βCD; (c) HPβCD; (d) PVA; (e) CMC-Na; (f) PXM-188; (g) DIF/βCD (1:2); (h) DIF/HPβCD (1:2); (i) DIF/βCD (1:2) PVA 10%; (j) DIF/βCD (1:2) CMC-Na 10%; (k) DIF/βCD (1:2) PXM-188 10%; (l) DIF/HPβCD (1:2) PVA 10%; (m) DIF/HPβCD (1:2) CMC-Na 10%; (n) DIF/HPβCD (1:2) PXM-188 10%.