Formulation and development of release modulated colon targeted system of meloxicam for potential application in the prophylaxis of colorectal cancer.

Abstract

The objective of the present study was to develop a colon targeted system of meloxicam for potential application in the prophylaxis of colorectal cancer. Efficacy of selective cyclooxygenase-2 inhibitors has been proven in colorectal cancer. Meloxicam is a selective cyclooxygenase-2 inhibitor with pH-dependent solubility. To achieve pH-independent drug release of meloxicam, pH modifying agents (buffering agents) were used. Meloxicam tablets containing polyethylene oxide were dually coated with ethyl cellulose containing hydrophilic material, polyethylene glycol as an inner coating layer and methyl acrylate, methyl methacrylate, and methacrylic acid copolymer (Eudragit® FS 30D) as outer coating layer for colon targeting. Optimized tablet formulations demonstrated good potential to deliver the drug to the colon by successfully exhibiting a lag time of 5 h during in vitro drug release study. An in vivo evaluation study conducted to ascertain pharmacokinetic parameters in rabbits revealed that the onset of drug absorption from the coated tablets (T(lag time) = 4.67 ± 0.58 h) was significantly delayed compared to that from the uncoated tablets. The AUC(0→)(t) and AUC(0→∞) for coated tablets were lower than of uncoated tablets, although the difference was not significant (p > 0.01). The roentgenography study revealed that the tablet remained intact, until it reached the colon (5 h), which demonstrates that the system can efficiently deliver the drug to the colon. This study demonstrated that a meloxicam-loaded colon targeted system exhibited promising targeting and hence may be used for prophylaxis of colorectal cancer.

• Authors: Mayur M Patel, Avani F Amin
• Journal: Drug delivery (Drug Deliv) Vol. 18 Issue 4 Pg. 281-93 (May 2011) ISSN: 1521-0464 [Electronic] England
• PMID: 21138335 (Publication Type: Journal Article)

Chemical References

• Cyclooxygenase 2 Inhibitors
• Delayed-Action Preparations
• Polymethacrylic Acids
• Tablets
• Thiazines
• Thiazoles
• methylmethacrylate-methacrylic acid copolymer
• Polyethylene Glycols
• ethyl cellulose
• Cellulose
• Meloxicam

Topics

• Animals
• Cellulose (analogs & derivatives, chemistry)
• Chemistry, Pharmaceutical (methods)
• Colon (drug effects, metabolism)
• Colorectal Neoplasms (prevention & control)
• Cyclooxygenase 2 Inhibitors (chemistry, pharmacology)
• Delayed-Action Preparations
• Drug Delivery Systems (methods)
• Drug Stability
• Hydrogen-Ion Concentration
• Meloxicam
• Polyethylene Glycols (chemistry)
• Polymethacrylic Acids (chemistry)
• Rabbits
• Solubility
• Tablets (chemistry)
• Thiazines (administration & dosage, chemistry, pharmacokinetics)
• Thiazoles (administration & dosage, chemistry, pharmacokinetics)