An in vitro and in vivo investigation into the suitability of compression coated tablets of indomethacin for the treatment of rheumatoid arthritis which follow circadian rhythms

Abstract

Objective: The aim of this study was to develop chronotherapeutic drug delivery system of indomethacin using polyethylene oxide (PEO) with a predetermined lag time of 6 h by compression coating technique.

Materials and methods: Solid dispersions (SD) of indomethacin were prepared using novel carrier sucrose fatty acid ester (SFE 1815) to increase the in vitro dissolution. The optimized SD was formulated as immediate release core tablet which were further coated with PEO (WSR Coagulant or WSR N12 K) using compression coating technique. Compression coated tablets formulated with PEO WSR Coagulant in 1:1.7 ratio of core tablet weight and coating polymer was considered as optimized formulation, which was further characterized by differential scanning calorimetry, X-ray diffractometry, Fourier transformed infrared spectroscopy, and scanning electron microscopy.

Results: The results indicated that there was no chemical incompatibility and slight change in surface properties. C_max, area under the curve (AUC_0-t), and T_max following oral ingestion of commercial capsule (Indocap) and optimized formulation (CT 4) were found to be 1973.18 ± 36.89 ng/mL, 11090.09 ± 131.21 ng/mL/h, 0.99 ± 0.02 h and 2115.46 ±6 2.61, 10413.14 ± 299.66 ng/mL/h, 7.00±0.02 h, respectively.

Conclusion: Unaltered AUC_0-t and C_max, but delayed T_max indicated clear lag time before immediate release of drug which is suitable for treating rheumatoid arthritis following circadian rhythm.

Keywords:

• Circadian rhythms
• chronotherapeutic drug delivery system
• sucrose fatty acid ester 1815
• compression coated tablets
• pharmacokinetic evaluation

Acknowledgment

The author A. S. Songa is thankful to UGC (University Grants Commission, India) for awarding senior research fellowship for carrying out this research work. One of the authors A. S. Songa is thankful to B. Janaki Ram and B. Sudhakar for providing valuable information to carry out this research work. The author is also thankful to G. Sirisha for helping us out to take the photographs of the work.

Declaration of interest

The authors report no conflict of interest.