Polyelectrolyte-based solid dispersions for enhanced dissolution and pH-Independent controlled release of sildenafil citrate

Abstract

The aim of this study was to design a novel matrix tablet with enhanced dissolution and pH-independent controlled release of sildenafil citrate (SIL), a drug with pH-dependent solubility, by using solid dispersions (SDs) and polyelectrostatic interactions. SIL-loaded SDs were prepared using various polymeric carriers such as poloxamer 188, poloxamer 407, Soluplus®, polyvinylpyrrolidone (PVP) K 12, and PVP K 17 by the solvent evaporation method. Among these polymers, Soluplus® was found to be the most effective in SDs for enhancing the drug dissolution over 6 h in pH 6.8 intestinal fluid. SIL was well dispersed in Soluplus®-based SDs in an amorphous form. When the Soluplus®-based SDs were added in the tablet containing positively charged chitosan and negatively charged Eudragit® L100, the drug release rate was further modulated in a controlled manner. The charge density of the tablet was higher at pH 6.8 than at pH 1.2 due to the polyelectrostatic interaction between chitosan and Eudragit® L100. This interaction could provide a pH-independent controlled release of SIL. Our study demonstrates that a combinatory approach of Soluplus®-based SDs and polyelectrostatic interactions can improve the dissolution and pH-independent release performance of SIL. This approach could be a promising pharmaceutical strategy to design a matrix tablet of poorly water-soluble drugs for the enhanced bioavailability.

Keywords: Controlled release; Differently charged polymers; Enhanced dissolution; Polyelectrostatic interaction; Sildenafil citrate; Soluplus®-based solid dispersion.

Fig. 1

Effect of polymeric carriers on the dissolution rate of SIL in binary solid dispersions at pH 6.8 intestinal fluid (n = 3). (A) SIL:polymeric carrier = 1:2, (B) SIL:polymeric carrier = 1:1.

Fig. 2

SEM images of SIL (A), Soluplus® (B), (C) physical mixture of SIL and Soluplus® (C) and six different types of SIL-loaded SDs (D ∼ I).

Fig. 3

PXRD patterns of SIL (A), Soluplus® (B), (C) physical mixture of SIL and Soluplus® (C) and six different types of SIL-loaded SDs (D ∼ I).

Fig. 4

DSC thermograms of SIL (A), Soluplus® (B), (C) physical mixture of SIL and Soluplus® (C) and six different types of SIL-loaded SDs (D ∼ I).

Fig. 5

FT-IR spectrum of (A) chitosan, (B) Eudragit® L 100, (C) SIL, (D) Chitosan + SIL, (E) Eudragit® L 100 + SIL, (F) Chitosan + Eudragit® L 100 + SIL, and (G) the polyelectrostatic complexes between chitosan and Eudragit® L 100.

Fig. 6

Comparative release profiles of SIL-loaded SD3 and polymeric-based matrix tablets via polyelectrostatic interaction of differently charged polymers (n = 3).

Fig. 7

The changes of charge density of Soluplus®-based SD3 and polymeric-based matrix tablets in different media (A) deionized water, (B) gastric fluid (pH 1.2) and (C) intestinal fluid (pH 6.8) (n = 3)

Fig. 8

Mechanistic understanding of the designed matrix tablet containing SIL-loaded SDs simultaneously controlling drug solubility and release rate via polyelectrostatic molecular interaction.