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Postgraduate Medicine Aug 2015Topical formulations of nonsteroidal anti-inflammatory drugs (NSAIDs) are generally considered to be safer alternatives to oral NSAIDs due to lower systemic absorption.... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Topical formulations of nonsteroidal anti-inflammatory drugs (NSAIDs) are generally considered to be safer alternatives to oral NSAIDs due to lower systemic absorption. We conducted randomized, crossover studies that compared the pharmacokinetics (PK), bioequivalence and safety of topical diclofenac sodium 2% twice daily (BID), diclofenac sodium 1.5% four times daily (QID) and oral diclofenac sodium in healthy subjects.
METHODS
The results of three bioequivalence studies are reviewed. Healthy adult subjects (n = 76) applied topical diclofenac sodium 2% solution (40.4 mg/2 mL) BID; or 1.5% solution (19.3 mg/40 drops) QID to each knee for 7.5 consecutive days separated by a washout period. Subjects (n = 22) in one study also received oral diclofenac sodium 75 mg BID for 7.5 days. Plasma diclofenac concentrations were determined from serial blood samples collected on Days 1 and 8 (steady state), and diclofenac PK parameters were estimated by noncompartmental methods.
RESULTS
The studies demonstrated comparable bioequivalence between the 2% and 1.5% topical solutions as well as lower systemic exposure compared to oral dosing (approximately 93% less). Daily systemic exposure was comparable between the two formulations with only a 12% difference in the AUCss(0-24) (p = 0.140). Furthermore, both topical solutions demonstrated delayed elimination with a t(1/2) of 4- to 6-fold longer, as compared to oral diclofenac. The 2% solution provided more consistent dosing relative to the 1.5% solution when comparing AUCss(0-24) and Cmaxss across studies. Mild application site reactions were the most common treatment-emergent adverse event reported with topical diclofenac.
CONCLUSIONS
The steady-state PK profile of topical diclofenac 2% solution administered BID is similar to that of the 1.5% solution administered QID. Systemic exposure to diclofenac is substantially lower after topical application as compared to oral administration. (Study 2 was registered with ClinicalTrials.gov; NCT01202799; https://clinicaltrials.gov/ct2/results?term=01202799&Search=Search).
Topics: Administration, Cutaneous; Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Cross-Over Studies; Diclofenac; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Pharmaceutical Solutions; Therapeutic Equivalency
PubMed: 26077436
DOI: 10.1080/00325481.2015.1058689 -
International Journal of Pharmaceutics Sep 2016The effect of the glycolipid, hexadecyl-β-d-glucopyranoside, incorporated in microemulsions (ME(1)) towards the enhancement of skin absorption and skin permeation of...
The effect of the glycolipid, hexadecyl-β-d-glucopyranoside, incorporated in microemulsions (ME(1)) towards the enhancement of skin absorption and skin permeation of Diclofenac sodium (DS(2)) was evaluated. A Franz diffusion cell with a piece of pig's ear epidermis indicated that the optimized ME formulation with glycolipid (0.05wt%) exhibited significantly higher permeability than the conventional formulations. The releasing profiles of DS from ME formulations exhibited first order release kinetics resembling a diffusion controlled release model for the first 8h. Incorporating hexadecyl-β-D glucopyranoside in ME formulations shows significant potential as a delivery vehicle in the cosmetics and pharmaceutical industry.
Topics: Animals; Delayed-Action Preparations; Diclofenac; Drug Delivery Systems; Drug Liberation; Emulsions; Epidermis; Glycolipids; Organ Culture Techniques; Skin Absorption; Swine
PubMed: 27477103
DOI: 10.1016/j.ijpharm.2016.07.047 -
AAPS PharmSciTech Aug 2020Diclofenac sodium is a potent NSAID, classified under BCS class II category having a poor aqueous solubility. Recently, its injectable formulation got banned and...
Diclofenac sodium is a potent NSAID, classified under BCS class II category having a poor aqueous solubility. Recently, its injectable formulation got banned and withdrawn from the market due to its severe nephrotoxicity caused by the use of synthetic surfactant, i.e. Transcutol-P as solubilizer. Therefore, the present study was aimed to prepare Transcutol-P free injectable using Vitamin E TPGS as a biosurfactant which is in list of inactive ingredients by US-FDA. Various cost effective aqueous injectable formulations were prepared by mixed solvency method that were characterized and optimized for different in vitro quality control parameters. Further, ex vivo hemolytic study showed the increased safety (23.4 ± 1.6%) of optimized formulation as compared with its commercial counterpart (100 ± 4.2%) at 75 mg/ml. Furthermore, in vivo acute and sub-acute toxicity study demonstrated an increase in LD to 123.75 ± 6.2 mg/kg to that of a commercial counterpart (109.96 ± 5.5 mg/kg). In addition, optimized formulation demonstrated better mean residence time and area under curve when compared with commercial test group, respectively. Moreover, optimized formulation was also evaluated for its therapeutic efficacy. The results obtained from acetic acid-induced writhing test in albino mice showed 78 ± 2.1% protection from writhes after 120 min, whereas the commercial formulation had only 48.3 ± 1.9% protection. Additionally, carrageenan-induced rat paw edema model also confirmed the better anti-inflammatory activity of optimized aqueous injectable formulation than its commercial counterpart. Thus, the developed aqueous injectable formulation of diclofenac is free from toxic Transcutol-P with enhanced safety and therapeutic efficacy.
Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Drug Compounding; Female; Male; Mice; Rats; Rats, Wistar
PubMed: 32748022
DOI: 10.1208/s12249-020-01729-6 -
Pakistan Journal of Pharmaceutical... Sep 2018The objective of present study was to develop and evaluate polyethylene glycol (PEG) based diclofenac sodium suppositories. This study used water soluble PEG bases...
The objective of present study was to develop and evaluate polyethylene glycol (PEG) based diclofenac sodium suppositories. This study used water soluble PEG bases (1000, 4000 and 6000) in different combinations to formulate suppositories, which were further subjected for their physicochemical properties evaluation such as weight variation, average melting point, content uniformity and disintegration. Dissolution test was used to perform the in vitro release rate studies of the suppositories. The suppository (P3) containing PEG-6000 (50%) and PEG-4000 (50%) exhibited rapid in vitro release rate of diclofenac sodium. Moreover, homogeneous distribution of diclofenac sodium is found in all six formulations. The in vitro release patterns of diclofenac sodium from the marketed Voltral suppository (100mg) and formulated suppositories were also compared and found in standard limits.
Topics: Diclofenac; Drug Development; Drug Evaluation, Preclinical; Polyethylene Glycols; Suppositories
PubMed: 30150172
DOI: No ID Found -
The Journal of International Medical... 1975A short-term trial has been performed under double-blind conditions in 50 adult patients with rheumatoid arthritis to compare diclofenac sodium (Voltaren) with both... (Clinical Trial)
Clinical Trial Comparative Study
A short-term trial has been performed under double-blind conditions in 50 adult patients with rheumatoid arthritis to compare diclofenac sodium (Voltaren) with both indomethacin and placebo for efficacy and tolerability. The duration of the trial was two weeks and was a between-patient comparison of 25 mg t.i.d. diclofenac sodium, 25 mg t.i.d. indomethacin or placebo using a double-dummy technique. Forty-eight patients completed the trial. In the majority of parameters examined, diclofenac sodium was superior to placebo and indomethacin in therapeutic effect. One patient was withdrawn from the trial because of intolerance to indomethacin and one other because of severe joint pain under indomethacin therapy. Neither active compound caused clinically significant changes in blood picture or urine analysis.
Topics: Adult; Arthritis, Rheumatoid; Diclofenac; Female; Humans; Indomethacin; Male
PubMed: 162669
DOI: 10.1177/030006057500300301 -
AAPS PharmSciTech Apr 2022Topical microemulsion (ME) might provide a novel and advanced transdermal delivery system due to the enhances of drug solubility and permeability across the stratum...
Topical microemulsion (ME) might provide a novel and advanced transdermal delivery system due to the enhances of drug solubility and permeability across the stratum corneum. Foams are topical delivery systems that have excellent patient compliance, acceptability, and preference. Therefore, this study aimed to investigate a foamable microemulsion as an alternative topical and transdermal dosage form for diclofenac sodium (DS). The physicochemical properties (optical clarity, percentage transmittance, homogeneity, consistency of formulation, particle size, zeta potential, conductivity, viscosity, and morphology, etc.) of the DS-loaded ME were investigated. The foam stability of both drug-free ME and DS-loaded ME was measured. The foam quality was evaluated, and the chemical stability over 90 days was determined. Franz diffusion cells were employed to assess the in vitro drug release of a foamed DS-loaded ME and compared with a commercial topical product. A foamable and stable DS-loaded ME that maintained small particle sizes and constant zeta potential and was transparent and translucent in appearance after 90 days was successfully produced. The foam of the DS-loaded ME was physically more stable compared to the drug-free foam. The foam had an increased drug release rate compared to the commercial product. The foamable DS-loaded ME has a great potential to enhance the transdermal delivery of DS after topical administration. Foamed DS-loaded ME is a promising alternative to the current topical formulation of DS.
Topics: Administration, Cutaneous; Diclofenac; Drug Liberation; Emulsions; Humans; Solubility
PubMed: 35378669
DOI: 10.1208/s12249-022-02258-0 -
International Journal of... 2023The occurrence of pharmaceutical pollutants in aqueous media has increased where significant research is being conducted to eliminate these toxic compounds. In the...
The occurrence of pharmaceutical pollutants in aqueous media has increased where significant research is being conducted to eliminate these toxic compounds. In the present study, Tetradecyltrimethylammonium bromide (TTAB) modified agri-waste (CCW) was prepared to investigate the removal of diclofenac sodium (DCF) from aqueous solution in the batch process for the first time. Physical and chemical characterizations of as-prepared adsorbent were conducted using field emission scanning electron microscopy, Fourier-transform infrared spectroscopy, N adsorption-desorption, and point of zero charge analysis. Besides, the effect of the main parameters that affect the adsorption process, i.e., adsorbent dosage (0.25-6 g/L), contact time (0-300 min), initial DCF concentration (10-500 mg/L), and pH of the solution, were investigated. Furthermore, the resulted data were analyzed using various kinetic and isotherm models. The Pseudo-second-order model with = 0.9981 showed the highest agreement with kinetic behavior. Also, the maximum adsorption capacity of DCF is 93.65 mg/g, according to the Langmuir isotherm. In acidic media, the adsorption capacity reached the highest value (44.69 mg/g). As a result, this study revealed that the agri-waste material could be modified and, as a low-cost adsorbent, have promising adsorption potential to remove pharmaceutical contaminants from the aqueous solution.
Topics: Diclofenac; Cuminum; Adsorption; Water Pollutants, Chemical; Hydrogen-Ion Concentration; Biodegradation, Environmental; Thermodynamics; Water; Kinetics; Spectroscopy, Fourier Transform Infrared; Surface-Active Agents; Pharmaceutical Preparations
PubMed: 36006042
DOI: 10.1080/15226514.2022.2113367 -
Carbohydrate Polymers Feb 2017This study was conducted to investigate the effect of gamma irradiation on physicochemical properties of N-trimethyl chitosan (TMC), diclofenac sodium (DC) and...
This study was conducted to investigate the effect of gamma irradiation on physicochemical properties of N-trimethyl chitosan (TMC), diclofenac sodium (DC) and diclofenac sodium loaded N-trimethylchitosan nanoparticles (DC-TMCNs), and to determine suitable doses of gamma rays for sterilization of DC-TMCNs. Physicochemical properties of TMC, DC and DC-TMCNs before and after exposure to gamma rays at various doses were investigated. It was found that gamma irradiation at doses of 5-25kGy did not cause any significant changes in physical and chemical properties of TMC, DC and DC-TMCNs. The bioburden of DC-TMCNs was 1.5×10 CFU/vial. The initial contaminating bacteria were radiosensitive bacteria. A number of microorganisms was reduced to 10 after exposure to 9.9kGy of gamma rays. Therefore, DC-TMCNs could be sterilized by gamma irradiation at a dose of 10kGy, which did not alter their physicochemical properties and did not produce any substances toxic to the eye.
Topics: Administration, Ophthalmic; Animals; Cell Line; Chitosan; Cornea; Diclofenac; Nanoparticles; Ophthalmic Solutions; Rabbits; Sterilization
PubMed: 27987968
DOI: 10.1016/j.carbpol.2016.10.029 -
Journal of the European Academy of... Jan 2009Disseminated superficial actinic porokeratosis (DSAP) is a chronic cutaneous disorder of keratinization for which there is no known cure. Current therapies are often...
BACKGROUND
Disseminated superficial actinic porokeratosis (DSAP) is a chronic cutaneous disorder of keratinization for which there is no known cure. Current therapies are often ineffective, painful, or unappealing.
OBJECTIVE
To investigate the efficacy and safety of diclofenac sodium 3% gel for the treatment of DSAP.
METHODS
Seventeen adult patients with a diagnosis of DSAP applied diclofenac sodium 3% gel to a target area (forearm) twice daily for 3 months up to a maximum of 6 months in an open-label, multicentre pilot study. Target area lesion counts were performed monthly, and global lesion counts were performed at baseline and at weeks 12 and 24. A treatment satisfaction questionnaire was completed at weeks 12 and 24.
RESULTS
Thirteen patients completed 12 weeks of treatment and 10 completed 24 weeks. Among patients who completed 12 weeks, there was a mean decrease of 4% in target area lesions, while a mean increase of 12% was noted in global lesions. Among patients who completed 24 weeks, there was a mean increase of 19% in global lesions, but only a 10% increase noted in the target area. Seven of 13 patients had a decrease in target area lesions at week 12 and 3 of 10 patients at week 24. Questionnaire responses indicated 6 out of 10 patients would use the medication again.
CONCLUSION
Target area DSAP lesions in the majority of patients treated with diclofenac sodium 3% gel (both 12 and 24 weeks) progressed to a lesser extent as compared to the global lesion count.
Topics: Adult; Diclofenac; Gels; Humans; Keratosis, Actinic; Pilot Projects; Porokeratosis; Surveys and Questionnaires
PubMed: 18702625
DOI: 10.1111/j.1468-3083.2008.02943.x -
Scandinavian Journal of Rheumatology.... 1978In a double-blind, between-patient trial the efficacy and tolerability of two new non-steroid anti-inflammatory analgesics-diclofenac sodium (Voltaren) 50 mg b.i.d. and... (Clinical Trial)
Clinical Trial Comparative Study
In a double-blind, between-patient trial the efficacy and tolerability of two new non-steroid anti-inflammatory analgesics-diclofenac sodium (Voltaren) 50 mg b.i.d. and naproxen 250 mg b.i.d.-were compared in hospitalised patients with rheumatoid arthritis. Both drugs had a clearly positive effect on the duration of morning stiffness, bilateral grip strength, pain at rest, and pain on movement. No statistically significant difference between the two drugs was found with respect to clinical efficacy. Three patients treated with diclofenac sodium reported unwanted effects, as compared with seven patients receiving naproxen. These unwated effects led to premature discontinuation of the treatment in one patient on naproxen. Thus, although both drugs were well tolerated, it appeared that diclofenac sodium caused somewhat fewer unwanted effects.
Topics: Adult; Arthritis, Rheumatoid; Clinical Trials as Topic; Diclofenac; Double-Blind Method; Drug Evaluation; Female; Humans; Male; Middle Aged; Naproxen; Phenylacetates
PubMed: 356247
DOI: 10.3109/03009747809097218