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

Ju-Hyeong Woo; Hai V Ngo; Hy D Nguyen; Myung-Chul Gil; Chulhun Park; Jun-Bom Park; Jing-Hao Cui; Qing-Ri Cao; Beom-Jin Lee

doi:10.1016/j.heliyon.2023.e23091

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

Heliyon. 2023 Nov 30;9(12):e23091. doi: 10.1016/j.heliyon.2023.e23091. eCollection 2023 Dec.

Authors

Ju-Hyeong Woo¹, Hai V Ngo¹, Hy D Nguyen¹, Myung-Chul Gil¹, Chulhun Park², Jun-Bom Park³, Jing-Hao Cui⁴, Qing-Ri Cao⁴, Beom-Jin Lee^{1

5}

Affiliations

¹ College of Pharmacy, Ajou University, Suwon 16499, Republic of Korea.
² College of Pharmacy, Jeju National University, Jeju 63243, Republic of Korea.
³ College of Pharmacy, Sahmyook University, Seoul 01795, Republic of Korea.
⁴ College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
⁵ Institute of Pharmaceutical Science and Technology, Ajou University, Suwon 16499, Republic of Korea.

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.