Evaluation of improved oral bioavailability of ritonavir nanosuspension

Karakucuk A., TEKSİN Z. Ş. , EROĞLU H., Celebi N.

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, vol.131, pp.153-158, 2019 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 131
  • Publication Date: 2019
  • Doi Number: 10.1016/j.ejps.2019.02.028
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.153-158
  • Keywords: Ritonavir, Nanosuspension, Microfluidization, Fasted/fed bioavailability, Point to point relation in IVIVC, DRUG, NANOCRYSTALS, SOLUBILITY, HYDROCHLORIDE, ENHANCEMENT, STABILIZERS, DISSOLUTION, RELEASE, ART


The main objective of this study was to evaluate the pharmacokinetics of ritonavir (RTV) nanosuspension in rats in both fed and fasted state in comparison with coarse powder, physical mixture and commercial product (Norvir (R)). The point to point relation model was generated between the results of in vitro dissolution and in vivo pharmacokinetic studies. The oral RTV nanosuspension was prepared with microfluidization method. Nanosuspension was obtained with 540-550 nm of particle size, 0.1-0.4 of particle size distribution and about -20 mV of zeta potential values. According to in vivo pharmacokinetic studies in rats, C-max and AUC(0-t) values in nanosuspension displayed an 8.9- and 12.5-fold increase compared to the coarse powder, and a 1.9- and 2.1-fold increase compared to the commercial product, respectively in the fed group. The point to point relation model showed that the correlation model was significant. It is concluded that nanosuspension is a promising drug delivery system to enhance oral bioavailability of ritonavir.