Determination of related substances in ketoprofen injection by RP-HPLC method.

The paper aims to establish a RP-HPLC method for the simultaneous determination of six related substances in ketoprofen injection. The separation was performed on a VP-ODS C18 column (4.6mm×250mm, 5µm) with the mobile phase of 6.8% phosphate buffer solution (adjusted to pH3.5 with 85% phosphoric acid)-acetonitrile-water (2:43:55,v/v/v) at a flow rate of 1.2mL•min-1. The detection wavelength and the injection volume were set at 233nm and 20µL, respectively. Impurity A and C were calculated by external standard method. Main component self-compare method with calibration factor was used to calculate impurity B, D, E, F and main component self-compare method without calibration factor was used to calculate unspecified impurity. Related substances and degraded substances were completely separated from ketoprofen. For impurity A and C, the linear range of determination were separately 0.06 µg•mL-1 ~ 3.6µg•mL-1 and 0.036µg•mL-1 ~ 2.4µg•mL-1 with the correlation coefficient of 0.9999. The average recoveries (n=9) were 98.13% (RSD=0.35%) and 96.32% (RSD=0.43%). The precision and repeatability for method were good. With reference to ketoprofen (retention time =10.06 min), the relative retention time of impurity B, D, E, F were 0.71, 1.46, 0.59, 2.13, respectively, and the relative correction factors were 0.962, 0.938, 0.957, 0.960, respectively. Finally, determined that the contents of impurity A could not be more than 0.3%, any of the contents of impurity B, C, D, E, F and unspecified impurities could not be more than 0.2%, sum of the contents of impurities other than A and C couldn't be more than 0.5%. The method was proved to be simple, rapid, accurate, sensitive and suitable for the simultaneous determination of six related substances in ketoprofen injection.

Expert Consensus on Clinical Use of an Orally Administered Dexketoprofen Plus Tramadol Fixed-Dose Combination in Moderate-To-Severe Acute Pain: A Delphi Study.

INTRODUCTION: In 2016, the orally administered fixed-dose combination of dexketoprofen 25 mg and tramadol 75 mg (DKP/TRAM FDC) was approved in Europe for short-term treatment of moderate-to-severe acute pain, an indication that encompasses a wide range of post-operative and non-surgical painful conditions. This has suggested the necessity to have a clearer indication on its clinical use, with the support of expert pain clinicians, working in different medical specialities, and reinforced by the data present in the literature. METHODS: With the aim of assisting clinicians in the use of DKP/TRAM FDC in daily practice, two rounds of a modified Delphi process were conducted. In the first round, a board of nine experts developed a series of consensus statements based on available evidence, and their clinical experience, with DKP/TRAM FDC. In the second round, 75 clinicians with extensive experience in pain management expressed individually their agreement with the statements, using a dedicated online platform. Consensus was defined as at least 70% agreement. RESULTS: Twenty-eight statements were developed. Of these, 19 reached the defined level of consensus. CONCLUSION: The agreed consensus statements may assist clinicians in applying the results of clinical studies and clinical experience to routine care settings, providing guidance for use of this new analgesic combination in moderate-to-severe post-operative and non-surgical acute pain. FUNDING: Menarini Group.

Pharmaceutical and in vitro therapeutic equivalence studies of ketoprofen enteric coated 100 mg tablets.

The objective of this study was to assess the quality of six different brands of enteric coated Ketoprofen 100 mg tablets, KPB2 to KPB6 are available in commercial market of Karachi, Pakistan, while KPB1 was obtained from international source. We performed different physico-chemical assessments i.e. weight variation, diameter, hardness, friability, thickness, disintegration, content uniformity, assay and dissolution test. Results of all the investigations were found to be in adequate limits. Also pharmaceutical equivalence was determined by selecting different tests and assay assessment. Furthermore, in vitro therapeutic equivalence was also estimated at phosphate buffer pH 6.8 and 7.5. Results were evaluated by one way ANOVA, model independent and model dependent methods. ANOVA results showed that release behaviour were found to be similar as p values >0.05, also KPB 1 - KPB6 followed Weibull model at different dissolution media. Results indicated that innovator and brands not only passes the pharmaceutical equivalence assessment but also comply with the in vitro therapeutic equivalence.

Tissue extraction and high-performance liquid chromatographic determination of ketoprofen entantiomers.

Local transcutaneous delivery of non-steroidal anti-inflammatory drugs avoids gastrointestinal side effects and concentrates drugs in the intended tissues. An extraction and HPLC method was developed for ketoprofen in skin, fascia and muscle. Tissue samples were homogenized in NaHCO3. After methylene chloride removal of lipids, the aqueous layer was acidified with HCl and back extracted into isooctane/isopropanol. Ketoprofen was derivatized with ethylchloroformate/S-(-)-alpha-phenylethylamine in triethylamine, then detected by HPLC. Ketoprofen recovery was linear (1-33 microg/g) and was detected in these tissues following in vivo cathodic iontophoresis (160 mA*min). This represents the first non-radioactive method for determination of ketoprofen in tissues following transcutaneous iontophoresis.

Long-term safety of ketoprofen in an elderly population of arthritic patients.

A total of 823 patients (620 women and 203 men) aged greater than or equal to 65 years (mean age: 72 years) with osteoarthritis (n = 642) or rheumatoid arthritis (n = 181) were enrolled in an international prospective study designed to assess the safety profile of ketoprofen, a propionic acid derivative, over a 12-month treatment period. The patients received a 200-mg, sustained-release tablet of ketoprofen once daily. At the end of the study, 521 patients (63.3%) remained on the drug regimen, whereas 302 patients (36.7%) had withdrawn from treatment for various reasons, including adverse reactions, inefficacy and improvement, or had been lost to follow-up. A total of 314 patients (38.2%) experienced at least one adverse event during the study. Most side effects involved the digestive system (232 patients [28.2%]), the central nervous system (33 patients [4.0%]) or the cardiovascular system (26 patients [3.2%]). Fourteen patients (1.7%) experienced gastrointestinal adverse events (e.g., ulceration and bleeding). Most of these events occurred during the first 3 months of the study. Thus, it may be concluded that sustained-release ketoprofen, 200 mg once daily, is safe for the long-term treatment of elderly arthritic patients.

Maintenance of blood pressure control in elderly hypertensives on ketoprofen.

In elderly patients, nonsteroidal anti-inflammatory drugs (NSAIDs) are often used concomitantly with antihypertensive agents. It is therefore important to assess the potential for interactions between NSAIDs and these agents. In a double-blind, placebo-controlled study, 40 elderly hypertensive patients treated with acebutolol or atenolol, together with frusemide, were randomized to receive either ketoprofen, 200 mg/day (50 mg q.i.d.), or matching placebo for 7 days. Arterial blood pressure and heart rate were monitored for a 24-hour period at baseline and at the end of treatment. Standard sphygmomanometric measurements of blood pressure and heart rate were conducted twice a day during the study. No clinically significant side effects or blood pressure or heart rate alterations were observed during the trial. The results indicate that ketoprofen does not interfere with blood pressure control in elderly hypertensive patients being treated with a combination of beta-blockers and diuretics.