ABSTRACT
Imatinib mesylate is a small molecule used in cancer therapy as a thyrosine kinase inhibitor. Dexketoprofen trometamol is a non-steroidal anti-inflammatory drug that has seen use in cancer therapy in combination with an anticancer drug to minimize tumor size and to reduce pain in patients. In the present study, imatinib mesylate and dexketoprofen trometamol were selected as potential model drugs to be used in combination. A new, simple and selective Ultra Performance Liquid Chromatography method was developed and validated to determine the drug substances in distilled water, in a pH 7.4 phosphate buffer and in Dulbecco's Modified Eagle Medium. The proposed method was developed using a BEH C-18 column with isocratic elution. A mixture of methanol:acetonitrile (80:20, v/v) and pH 9.5, 0.05 M ammonium acetate were (70:30, v/v) used as a mobile phase. Detection was carried out with a flow rate of 0.3 mL/min, a column temperature of 30°C and an injection volume of 20 µL. The method was validated considering linearity, accuracy, precision, specificity, robustness, detection limit and quantitation limit values, and was found to be linear in a range from 0.05 to 20.0 µg/mL for the three different media
Subject(s)
Validation Study , Imatinib Mesylate/antagonists & inhibitors , Pharmaceutical Preparations/analysis , Chromatography, Liquid/methods , Acetates/adverse effects , NeoplasmsABSTRACT
ABSTRACT A drug delivery system (DDS) with analgesic and antibacterial properties would be desirable for the local control of post-operatory pain and the prevention for surgical site infection (SSI). The objective of the present study was to evaluate the antinociceptive effect of the combination between dexketoprofen trometamol (DXT) and chlorhexidine gluconate (CHX) in the formalin pain model. Different doses of CHX were combined with DXT and were locally administered in rats paw simultaneously with 5% formalin dilution. Flinches were documented and the antinociceptive effect was calculated. The area under the curve of each experimental group were calculated and the % of antinociception were compared. The groups of CHX and DXT showed similar antinociceptive effect. The combination groups (DXT-CHX) showed higher antinociceptive effect that the one obtained with individual molecules. Besides the confirmation of DXT local antinociceptive properties, CHX also showed a positive effect; and an additive effect when combined with DXT
Subject(s)
Animals , Female , Rats , Pain Measurement/instrumentation , Analgesics/adverse effects , ChlorhexidineABSTRACT
Objective: To prepare dexketoprofen trometamol hydrogel patches, optimize the formula and evaluate in vitro transdermal properties.Methods: Dexketoprofen trometamol hydrogel patches were prepared with NP-800 as the hydrogel patch carrier, aluminum hydrochloride as the crosslinking agent, EDTA as the crosslinking modifier and glycerol as the moisturizing agent.The formula was screened by orthogonal design with the initial viscosity, holding force, peel strength and 12 h cumulative transdermal quantity as the evaluation indices to screen out the best formula.The transdermal absorption test was carried out with an improved Franz diffusion cells to compare the enhancement of Aznoe, oleic acid and menthanol on dexketoprofen trometamol hydrogel patches.Results: The best formula was as follows: the mass percentage of NP-800, glycerol, glycerol and EDTA was 5%, 0.3% , 25% and 0.15% , respectively.The transdermal enhancers had transdermal enhancement on dexketoprofen trometamol, and among them, 3% Azone had the most significant enhancement with the enhancing rate of 3.26.Conclusion: The preparation and formula of dextroxyprofen trometamol hydrogel patches are stable, reasonable and feasible.
ABSTRACT
Background & objectives: Patients frequently experience pain of moderate to severe degree during gynaecologic procedures. This prospective, randomized, placebo-controlled trial was aimed to investigate the analgesic efficacy of preoperative oral dexketoprofen trometamol, intravenous paracetamol, lidocaine spray, pethidine and diclofenac sodium on fractional curettage procedure. Methods: A total of 144 mutiparous women were randomly allocated to one of the six groups. The first group (control group) consisted of 22 participants and they did not receive any treatment. The second group had 26 participants receiving oral 25 mg dexketoprofen trometamol. The 23 participants of the third group received two puff lidocaine sprays on cervical mucosa. The forth group consisted of 25 participants receiving 100 mg pethidine. In the fifth group, the 23 participants received 1000 mg intravenous paracetamol and the sixth group consisted of 25 participants receiving diclofenac sodium. Results: Pethidine was the best choice for reducing pain score during curettage procedure (t2:intra-operative). All analgesic procedures were significantly effective in reducing pain during postoperative period (t3). Significant pain reduction was achieved for both intra- and postoperative period by using analgesics. Interpretation & conclusions: The results of our study showed that lidocaine puffs provided the best pain relief than the other analgesics used. Therefore, lidocaine may be considered as the first choice analgesic in fractional curettage (NCT ID: 01993589).
ABSTRACT
Background & objectives: Intra-articular (ia) injections of local anaesthetics and non-steroidal anti-inflammatory drugs (NSAID’s) are simple and efficient to ensure post-operative analgesia but some of these have toxic effects on the synovium and cartilage. Dexketoprofen is recently introduced S-enantiomer of ketoprofen with a better analgesic and side effect profile. This study was done to evaluate the possible toxic effects of dexketoprofen trometamol on knee joint cartilage and symovium in vitro and in vivo. Methods: Forty one Sprague-Dawley rats were anaesthetized by ketamine. Dexketoprofen trometamol (0.25 ml) was injected into the right knee joint of the 35 rats and 0.25 ml serum physiologic into the left knee joint of the same animals. Six rats were sham operated. Thirty five animals were randomly divided into five equal groups. Seven animals were sacrified at 24th, 48th hours and 7th, 14th, and 21st days of the injections. Haematoxylin eosin stained sections from the knee joints were evaluated for the signs of inflammation according to five point scale. Primary chondrocytes were isolated from the articular cartilages of rats for in vitro studies. Cells were exposed to 0.25 ml dexketoprofen trometamol or 0.25 ml dexketoprofen medium mixture at 1:1 ratio for 15, 30, 45 and 60 min. Cell viability was determined by 3-(4, 5- dimethylthiazole-2-yl)-2.5-diphenyl tetrazolium bromide (MTT) assay, 24, 48 and 72 h after drug treatment. Results: No significant histopathologic differences were found between dexketoprofen trometamol and physiologic serum (control) applied joints at all time intervals in in vivo study. Cell proliferation in dexketoprofen trometamol treated chondrocytes was inhibited for all time intervals compared to control. In dexketoprofen-medium mixture groups significant differences were only seen 24 h after the 30 and 45 min application of medium: drug mixture. Interpretation & conclusions: Intra-articular application of dexketoprofen trometamol into the rat knee joints did not cause significant histopathological changes, but its in vitro application in primary chondrocyte culture caused significant cytotoxicity. The effects of dexketoprofen at different concentrations need to be further investigated in culture of rat and human chondrocytes.