Comparative assessment of effectiveness of ketoprofen and ketoprofen/beta-cyclodextrin complex in two experimental models of inflammation in rats

Abstract

Oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) can lead to adverse effects such as gastrointestinal distress. The complexation of different groups of active substances with b-cyclodextrin (b-CD) has drawn considerable interest over recent years. The purpose of this study was to analyze the ketoprofen/b-cyclodextrin (K/b-CD) conjugate complex as well as to assess its anti-inflammatory effect after oral administration (doses of 30 mg/m 2 and 15 mg/m 2 of body surface), compared with ketoprofen. The studies were done on two models of experimentally-induced acute inflammation in rats (n ¼ 48, 6/group), by means of intraplantar administration of a 10% aqueous kaolin suspension and intraperitoneal administration of a 1% sodium thioglycolate solution. The dynamics of the acute inflammatory process and the anti-inflammatory effects were monitored using plethysmometric determinations after 3, 6, 9, 12, 24 and 48 h (plantar inflammation), and the absorbance of the exudates (spectrophotometrically read) and nucleated cell counts after 24 h (peritoneal inflammation). The coupling of ketoprofen with b-CD resulted in increased solubility (100% in 60 min) of the newly-formed product, which further resulted in a higher bioavailability compared with ketoprofen (<40% in 120 min). In both models of experimentally-induced inflammation, the K/b-CD complex had a higher anti-inflammatory activity than ketoprofen.

Inclusion Complexes of Non-Steroidal Anti-Inflammatory Drugs with Cyclodextrins: A Systematic Review

“…On the other hand, these drugs can present significant side effects, such as increased cardiovascular risk and stimulation of gastric ulcer formation [121]. Grecu and collaborators [68] demonstrated that ketoprofen/β-CD complex presented a stronger anti-inflammatory activity than ketoprofen pure in rat models of paw edema and peritonitis. Similar findings were obtained by Auda [88], Alshehri et al [123], and Ammar et al [70] using inclusion complexes of nimesulide-Me-β-CD, flufenamic acid-β-CD, and lornoxicam-β-CD/lornoxicam-HP-β-CD, respectively.…”

Strategies to Improve the Transdermal Delivery of Poorly Water-Soluble Non-Steroidal Anti-Inflammatory Drugs

“…While B-CD has the lowest aqueous solubility of the three most common CD types, this can be improved through modification of the molecule via substitution of the hydroxyl groups, with hydroxypropyl derivatives being commonly used [134]. Beta-CDs have been successfully used to increase the solubility of other coxib NSAIDs, such as celecoxib [131,135,136], rofecoxib [137], and valdecoxib [126], as well as many traditional NSAIDs (ketoprofen [138], tolfenamic acid [139], meloxicam [140], and piroxicam [141]). However, while CDs can improve the solubility of NSAIDs in a formulation, the transdermal permeation of CDs when used alone is limited [142], necessitating the addition of other permeation-enhancing excipients when aiming to achieve systemic drug concentrations.…”

Short Review on the Biological Activity of Cyclodextrin-Drug Inclusion Complexes Applicable in Veterinary Therapy

“…Ketoprofen [ 62 , 63 ], which is commonly used in colic in horses, tolfenamic acid [ 64 ], meloxicam [ 65 , 66 ], carprofen [ 67 ] or piroxicam [ 68 ], which are used in dogs and cats to relieve pain and inflammation associated with osteoarthritis, complexed with β-CD or HP-β-CD ultimately resulted in increased bioavailability with improved analgesic and anti-inflammatory activity and decreased ulcerogenic effect.…”

“…Many other studies have used CDs (especially β-CD and HP-β-CD) to improve the water solubility and increase the bioavailability of NSAIDs [ 69 ], It can be mentioned that the increased solubility was associated with an improved bioavailability [ 73 ], with an effective analgesia, with increased anti-inflammatory activity, but also with the reduction of adverse reactions [ 62 ]. Therefore, strategies aimed at improving the safety and efficacy of NSAIDs, such as CD preparations, have a fundamental impact on anti-inflammatory therapy.…”