Oral pH-triggered colon-specific ketoprofen loaded microspheres for the better management of early morning symptoms associated with rheumatoid arthritis. Part II: Pharmacokinetic and pharmacodynamic assessment in rats

Abstract

Objective

To evaluate the effectiveness of oral pH-triggered colon-specific ketoprofen-loaded microspheres (C-SKLMs) in managing early morning symptoms of rheumatoid arthritis (RA) through pharmacokinetic and pharmacodynamic assessments.

Methods

Pharmacokinetic parameters, including T_max, C_max, and mean residence time (MRT), were analyzed in animals treated with C-SKLMs and compared with pure ketoprofen. Pharmacodynamic evaluations assessed the ability of C-SKLMs to address early morning RA symptoms effectively by aligning drug release with the body's circadian rhythm.

Results

The T_max for the C-SKLMs group (9.33 ​± ​1.63 ​h) was significantly prolonged compared to pure ketoprofen (2 ​h), indicating delayed drug release tailored to circadian needs. The C_max for C-SKLMs (5.94 ​± ​1.20 ​μg/mL) was lower than that of pure ketoprofen (12.4 ​± ​3.00 ​μg/mL), demonstrating a controlled-release profile. Additionally, the MRT for C-SKLMs (12.96 ​± ​1.42 ​h) was approximately 1.4 times longer than for pure ketoprofen (9.44 ​± ​0.69 ​h), emphasizing extended drug release. Pharmacodynamic evaluations supported the superior effectiveness of C-SKLMs in managing early morning RA symptoms compared to pure ketoprofen.

Conclusion

C-SKLMs demonstrated significant potential to improve the management of early morning symptoms associated with RA through controlled, extended, and circadian-tailored drug release, making them a promising therapeutic approach.