Development and in vitro/in vivo evaluation of etodolac controlled porosity osmotic pump tablets.

The aim of the current work was the design and evaluation of etodolac controlled porosity osmotic pump (CPOP) tablets exhibiting zero-order release kinetics. Variables influencing the design of (1) core tablets viz., (a) osmogent type (sodium chloride, potassium chloride, mannitol, and fructose) and (b) drug/osmogent ratio (1:0.25, 1:0.50, and 1:0.75), and (2) CPOP tablets viz., (a) coating solution composition, (b) weight gain percentage (1-5%, w/w), and (c) pore former concentration (5%, 10%, and 20%, v/v), were investigated. Statistical analysis and kinetic modeling of drug release data were estimated. Fructose-containing core tablets showed significantly (P < 0.05) more retarded drug release rates. An inverse correlation was observed between drug/fructose ratio and drug release rate. Coating of the optimum core tablets (F4) with a mixture of cellulose acetate solution (3%, w/v), diethyl phthalate, and polyethylene glycol 400 (85:10:5, v/v, respectively) till a 4% w/w weight gain enabled zero-order sustained drug delivery over 24 h. Scanning electron microscopy micrographs of coating membrane confirmed pore formation upon contact with dissolution medium. When compared to the commercial immediate-release Napilac® capsules, the optimum CPOP tablets (F4-34) provided enhanced bioavailability and extended duration of effective etodolac plasma concentration with minimum expected potential for side effects in healthy volunteers.

Safety profile of etodolac in the elderly population.

A growing proportion of patients who require nonsteroidal anti-inflammatory drug (NSAID) therapy are elderly. Data from patients 65 years and older with osteoarthritis or rheumatoid arthritis show that etodolac is as well tolerated in elderly as in younger patients. Of 273 elderly patients treated with at least 600 mg daily, only 12% withdrew because of adverse events, a rate similar to that in the younger age-group. Notably, the incidence of etodolac-associated gastrointestinal events is no higher in elderly than in younger patients. Etodolac was no different from diclofenac and piroxicam regarding incidence and type of adverse events. In both short- and long-term studies, the 400-mg and 600-mg sustained-release etodolac formulations were well tolerated in elderly and younger patients. Thus, etodolac appears to be a first-line choice in elderly patients.

Meta-analysis of three double-blind comparative trials with sustained-release etodolac in the treatment of osteoarthritis of the knee.

A meta-analysis was done with the final data from three trials that provided the first results relating to efficacy and safety of the new sustained-release (SR) formulation of etodolac versus established nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of osteoarthritis (OA) of the knee. The studies were 4-week, double-blind, randomized, parallel-group comparisons of etodolac SR 600 mg (119 patients) against diclofenac SR 100 mg (54 patients), tenoxicam 20 mg (46 patients), or piroxicam 20 mg (18 patients). The primary efficacy parameters (assessed after 2 and 4 weeks of treatment) were physicians' and patients' overall assessments of patients' condition, night pain, and pain intensity. All patients had radiographic and clinical evidence of OA of the knee. For the meta-analysis, the data from the individual etodolac SR studies were pooled and compared with the pooled data for diclofenac SR, tenoxicam, and piroxicam. The homogeneity of the treatments across studies and the changes from baseline between groups were tested using a Cochran-Mantel-Haenszel test and an analysis of variance, including "study," "treatment," and "center within treatment" effects and their interaction. The analysis for the efficacy parameters was based on the final assessment during therapy (last visit). At baseline, the two treatment groups were comparable. Improvement rates were high in both groups (range, 68-81%), indicating that treatments were effective for most patients. No significant treatment difference was observed for the patients' overall assessment, night pain, or pain intensity. Both etodolac SR and the reference preparations were well tolerated. No clinically significant changes were noted in the laboratory data.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of the efficacy of etodolac SR (Lodine SR) and etodolac (Lodine) in patients with rheumatoid arthritis or osteoarthritis.

The efficacy and safety of a sustained-release (SR) formulation of etodolac were compared with those of conventional etodolac in two separate, randomized, double-blind, multicenter, 6-week trials. This report presents an interim analysis of the data from these studies. One study included 174 patients with rheumatoid arthritis (RA): 58 received etodolac SR 400 mg once daily (q.d.), 59 received etodolac SR 600 mg q.d., and 57 received etodolac 200 mg twice daily (b.i.d.). The second study included 230 patients with osteoarthritis (OA): 80 patients received etodolac SR 400 mg q.d., 76 received etodolac SR 600 mg q.d., and 74 received etodolac 300 mg b.i.d. Efficacy was evaluated by physician's global and patient's global assessment (both studies), number of painful joints (RA study), number of swollen joints (RA study), pain intensity (OA study), and weight-bearing pain (OA study). The interim analyses of the data from the studies indicates that all three regimens produced significant improvements from baseline in all mean efficacy values at each assessment; there were no significant differences between the treatment groups. The incidence of study events, except for dyspepsia, was comparable among the treatment groups in each study; dyspepsia occurred at a significantly lower rate in patients treated with etodolac SR than in patients treated with the conventional formulation of etodolac. We conclude that etodolac SR is as effective and safe as conventional etodolac for the treatment of patients with RA or OA.

Meta-analysis of two double-blind comparative studies with the sustained-release form of etodolac in rheumatoid arthritis.

A meta-analysis was done with the data from two studies that provided the first efficacy and safety results for the new sustained-release (SR) formulation of etodolac versus established nonsteroidal anti-inflammatory drugs in patients with rheumatoid arthritis (RA). The studies were 4-week, double-blind, multicenter, randomized, parallel-group comparisons of etodolac SR 600 mg (102 patients) with either diclofenac SR 100 mg (65 patients) or piroxicam 20 mg (35 patients). The data for etodolac SR were pooled and compared with the pooled data for the comparators. The primary efficacy assessments (weeks 2 and 4) were physician and patient overall evaluation of the patient's condition, number of painful/tender joints, and number of swollen joints. Patients met at least five of the American Rheumatism Association diagnostic criteria and were within Steinbrocker progression stage I, II, or III and functional class I, II, or III. The homogeneity of the treatment groups across studies and the changes from baseline between groups were tested using a Cochran-Mantel-Haenszel test and an analysis of variance including "study," "treatment," and "center within treatment" factors and their interaction. The efficacy analysis was based on the final assessment during therapy (last visit). The patients in the etodolac SR group were older than those in the comparators group (P = 0.032), and there were more patients over 65 years of age in the etodolac SR group than in the comparators group (31% versus 14%, respectively; P = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

Worldwide experience with etodolac (Lodine) 300 mg b.i.d. in the treatment of osteoarthritis.

Worldwide experience with the conventional formulation of etodolac (300 mg b.i.d.) was reviewed in 12 randomized, double-blind, parallel-group studies in patients with osteoarthritis (OA) of the hip or knee. The studies were conducted in 13 countries at 59 sites, and 1289 patients were enrolled. The results of 9 comparative and 3 placebo-controlled clinical studies were examined to compare the efficacy and safety of etodolac versus piroxicam, naproxen, indomethacin, indomethacin sustained-release (SR), and diclofenac SR. Efficacy assessments were made at pretreatment screening, baseline, and every 2 weeks thereafter during treatment until study completion up to 4, 6, or 8 weeks. The primary efficacy assessments were the patient's and physician's global evaluations, pain intensity and night pain, or joint tenderness and walking pain. Safety was assessed with reference to study events, reports of laboratory results, and vital signs measurements. Patients in all active treatment groups showed prompt response to therapy. According to the physicians' global evaluation, at least 64% of all etodolac-treated patients and 62% of all active-reference preparation-treated patients had improved by the end of the study. Similar results were seen in the patients' global evaluation. All of the study drugs were well tolerated. Eight (8%) percent of the etodolac-treated patients withdrew because of study events. The proportions of patients treated with active reference preparations and placebos who withdrew because of study events ranged from 3% to 18%.(ABSTRACT TRUNCATED AT 250 WORDS)