Synthesis and in‐vivo taste assessment of meloxicam pivalate

Abstract

Meloxicam (MX), a nonsteroidal anti-inflammatory drug, widely used to treat arthritis, has a very bitter taste. Chemical modification of the bitter functionality was achieved by synthesis of a prodrug, meloxicam pivalate (MXP). Taste improvement was evaluated using single bottle-test rat model. It was found that palatability of MXP solution improved significantly as compared to MX.

KEYWORDS:

• Meloxicam (MX)
• prodrug
• meloxicam pivalate (MXP)
• rat model
• and in-vivo taste assessment

Acknowledgments

Bandoo Chatale would like to thank UGC-BSR, India, for the Research Fellowship and Lupin Pharmaceutical, Pune, India for gift sample. Authors are also thankful to All India Council for Technical Education (RPS fund, 2014-15) for HPLC procurement.

Disclosure statement

The authors declare not having competing financial interest.

Figure 3a. ¹H NMR integration for meloxicam pivalate in CDCl3.

Figure 3b. ¹H NMR integration for meloxicam in DMSO-d6 (NMR shown chemical shift δ, at 3.49 due to HDO and 2.47 due to DMSO-d⁵].

Figure 4. Mass of meloxicam pivalate ester and meloxicam pivalate molecular weight: 435.

Figure 5a. Meloxicam pivalate.

Figure 5b. Meloxicam.

Figure 6. Rat drinking meloxicam pivalate solution after water deprivation.

Figure 7. In vivo taste assessment test sample volume consumption: *(p < 0.0001), significant difference in volume of the MX solution (day 3) consumed as compared to water (day 1, 4); @(p < 0.0001), significant difference in volume of the MX solution (day 3) consumed to sucrose solution (day 2, 5); and # (p < 0.0001), significant difference in volume of the MX solution (day 3) consumed as compared to MXP (day 6).

Figure 8. In vivo taste assessment test sample volume consumption: *(p < 0.05), significant difference in volume of the MX-HP-β-CD solution (day 3) consumed as compared to water (day 1, 4); @(p < 0.0001), significant difference in volume of the MX-HP-β-CD solution (day 3) consumed to sucrose solution (day 2, 5); and # (p < 0.05), significant difference in volume of the MX-HP-β-CD solution (day 3) consumed as compared to MXP (day 6).