Oral pH triggered colon-specific ketoprofen loaded microspheres for the better management of early morning symptoms associated with rheumatoid arthritis. Part I: Optimization, in-vitro, and ex-vivo characterization

Abstract

The primary goal of this research was to investigate pH-triggered colon-specific ketoprofen-loaded microspheres (C-SKLM) using Eudragit S-100 as a pH-dependent polymer. The formulation was optimized using the Box-Behnken design. The suggested C-SKLM formulation with the amount of ketoprofen = 189.09 mg, the amount of Eudragit-100 = 600 mg, and the paddle speed = 400 rpm showed a considerable particle size (106 µm), drug encapsulation efficacy (79.67%), and % cumulative drug release at 5th hr (8.62) and 10th hr (92.62) for oral administration. Microphotographs of scanning electron microscopy indicated that the optimized C-SKLM was smooth and spherical. The differential scanning calorimetry and X-ray powder diffraction studies have shown that ketoprofen was dispersed in the polymer in its optimized C-SKLM formulation, and the spectra from the Fourier transform infrared study have shown no significant drug-polymer interaction. Ex-vivo permeation studies on isolated rat gastro-intestinal segments revealed that the maximum amount of ketoprofen permeated after 2 h through the isolated stomach (0.559 ± 0.049 mg), small intestine (1.36 ± 0.226 mg), and colon (0.972 ± 0.068 mg) was observed for ketoprofen pure. In contrast, a significantly lesser amount of the drug was permeated through the stomach (0.1 ± 0.025 mg) and small intestine (0.28 ± 0.1 mg) than the colon (0.697 ± 0.23 mg) from the ketoprofen-loaded microspheres formulation. In-vitro and ex-vivo permeation studies suggest that the developed C-SKLM could be helpful for the effective management of early morning symptoms due to rheumatoid arthritis by delaying the release by targeting the colon.

Graphical Abstract

Keywords:

• Eudragit S-100
• Box-Behnken design
• microspheres
• colon-specific drug delivery
• ketoprofen

Acknowledgements

All the authors are thankful to Dr. Vasudha Bakshi, Head of the Institution, Prof. Dr. Prakash V Diwan, Director, and Dr. Palla Rajeshwar Reddy, Chairman, School of Pharmacy, Anurag University, Hyderabad, for their continuous support and for providing research facilities.

Disclosure statement

No potential conflict of interest was reported by the author(s).