Bioavailability of indomethacin-saccharin cocrystals

Min Sook Jung, Jeong Soo Kim, Min Soo Kim, Amjad Alhalaweh, Wonkyung Cho, Sung Joo Hwang, Sitaram P. Velaga

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

Objectives Pharmaceutical cocrystals are new solid forms with physicochemical properties that appear promising for drug product development. However, the in-vivo bioavailability of cocrystals has rarely been addressed. The cocrystal of indomethacin (IND), a Biopharmaceutical Classification System class II drug, with saccharin (SAC) has been shown to have higher solubility than IND at all pH. In this study, we aimed to evaluate the in-vitro dissolution and in-vivo bioavailability of IND-SAC cocrystals in comparison with IND in a physical mixture and the marketed product Indomee®. Methods Scale-up of the cocrystals was undertaken using cooling batch crystallisation without seeding. The chemical and physical purity of the up-scaled material was verified using high-performance liquid chromatography, differential scanning calorimetry and powder X-ray diffraction. The IND-SAC cocrystals and IND plus SAC were mixed with lactose and the formulations were placed into gelatin capsules. In-vitro dissolution studies were then performed using the rotating basket dissolution method. The intrinsic dissolution rate of IND and IND-SAC cocrystals was also determined. Finally, a bioavailability study for the formulations was conducted in beagle dogs. The plasma samples were analysed using high-performance liquid chromatography and the pharmacokinetic data were analysed using standard methodologies. Key findings The bulk cocrystals (i.e. scaled-up material) were chemically and physically pure. The in-vitro dissolution rate of the cocrystals was higher than that of IND and similar to that of Indomee® at pH 7.4 and pH 1.2. The in-vivo bioavailability of the IND-SAC cocrystals in dogs was significantly higher (ANOVA, P < 0.05) than that of IND but not significantly different from Indomee® (ANOVA, P > 0.05). Conclusions The study indicates that the improved aqueous solubility of the cocrystals leads to improved bioavailability of IND. Thus, the cocrystals are a viable alternative solid form that can improve the dissolution rate and bioavailability of poorly soluble drugs.

Original languageEnglish
Pages (from-to)1560-1568
Number of pages9
JournalJournal of Pharmacy and Pharmacology
Volume62
Issue number11
DOIs
Publication statusPublished - 2010 Nov 1

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Bioavailability of indomethacin-saccharin cocrystals'. Together they form a unique fingerprint.

  • Cite this

    Jung, M. S., Kim, J. S., Kim, M. S., Alhalaweh, A., Cho, W., Hwang, S. J., & Velaga, S. P. (2010). Bioavailability of indomethacin-saccharin cocrystals. Journal of Pharmacy and Pharmacology, 62(11), 1560-1568. https://doi.org/10.1111/j.2042-7158.2010.01189.x