Laboratoires UPSA SAS

A novel, 96-well plate-based assay to measure drug solubility is presented.The drugs were introduced into the wells of a microtiter plate, and water was subsequently added to each well.Then, after stirring, the suspensions were filtered under vacuum in all wells at once and drug concentration was measured by spectrophotometry.Two protocols to measure the aqueous solubility under a 96-well plate format were investigated.When the drug powder was weighted directly into the wells (protocol A), solubility values were quite reproducible (variation coefficient below 28% for 5 experiments) and not significantly different from those reported in the literature.However, this procedure was rather cumbersome.To overcome the tedious weighting of the substance, another protocol was developed.The drug was first solubilized in acetonitrile, and an aliquot of the solution was pipeted into the well.Acetonitrile was subsequently evaporated before adding the water (protocol B).In that case, the results were more scattered than those using protocol A.In addition, this protocol is not suitable for efflorescent drugs, as seen with caffeine.However, for screening purposes, protocol B is easy to use and faster.For both protocols, it is recommended to use at least 4 wells for each drug to test.Approx. 15 drugs can be tested in a single 96-well plate.It is reproducible, accurate, and easy to use.It can also accommodate a large range of solubility (from approx. 0.003 to approx. 20 mg/mL in this study).

Objective: This double-blind randomized study was designed to compare paracetamol 500mg/codeine 30mg (PC) [3 times daily] plus diclofenac 50mg once a day with diclofenac 50mg twice a day (DI) over 7 days in two parallel groups of 30 patients with residual persisting pain despite adjusted basic therapy for rheumatoid arthritis (RA).Patients and Methods: Ten men and 50 women (aged 21 to 73 yr, mean 57 yr) with RA were included.The two groups were comparable before treatment.Efficacy was assessed by the patient every evening by: (a) pain scores rated on a 100mm visual analog scale [VAS]; (b) discomfort scores defining the activity level reduction [none, mild, moderate, severe]; (c) duration of morning stiffness; and (d) number of awakenings caused by the pain during the previous night.At the end of the study overall efficacy was assessed by the patient on a 5-point verbal scale and by the desire to continue the treatment (yes, no).Pain scores on VAS and on a 5-point verbal scale and Ritchie Index were assessed before [day 0 (D0)] and after (D7) treatment.Any adverse effects were recorded continuously during the study and overall tolerability was assessed at the end of the study.Results: Analgesic efficacy was not significantly different between the two groups on all criteria: global efficacy (good or very good: PC = 47%, DI = 44%), desire to continue the treatment (PC = 57%, DI = 47%), evolution of daily VAS pain score, difference from D0 to D7 on VAS (PC = -31.5mm, DI = -23.4mm) and the Ritchie index (PC = -2.2, DI = -2.2), duration of morning stiffness, number of awakenings.The number of patients presenting adverse effects (PC = 8, DI = 9), the number of withdrawals as a result of adverse effects causing cessation of treatment (PC = 3, DI = 1), and the overall tolerability assessment were not significantly different (good or very good: PC = 82%, DI = 87%).Conclusion: In RA, an inflammatory disease, the analgesic combination of paracetamol 500mg and codeine 30mg allowed a decrease in the NSAID dose for comparable relief of a residual persisting pain.

Percutaneously administered niflumic acid gel (Niflugel R, Laboratories UPSA, Rueil Malmaison, France) was compared to placebo in a double blind, placebo controlled, multicentre study in the treatment of acute upper and lower limb tendinitis. Fifty nine subjects were enrolled in three centres and were randomly allocated to receive treatment with 2.5% percutaneous niflumic acid gel or placebo gel applied three times daily for 7 days. Clinical evaluations were carried out on inclusion and after seven days of treatment. The variables measured were pain felt by the patient and the investigators' and patients' overall evaluation of the treatments' efficacy. The patients also kept a daily record of pain scores. Any adverse events that occurred were noted. The results showed that niflumic acid gel was significantly better than placebo in improving patient signs as regards overall efficacy ratings. Global evaluation of efficacy rated by the investigator showed that 25/29 patients (86.2%) were healed or improved in the niflumic acid gel group compared with 11/27 patients (40.7%) on placebo, p = < 0.01. The overall assessment of tolerance showed no difference between groups. Only two minor adverse effects were reported in patients treated with niflumic acid gel, and they did not require patients to stop treatment. The study findings indicate that treatment with topical niflumic acid gel is effective in the treatment of tendinitis and results in improved clinical signs at the end of 7 days.