• Archives of Pharmacal Research
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• 제25권4호
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• pp.534-540
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• 2002

To develop novel transdermal formulation for aceclofenac, microemulsion was prepared for increasing its skin permeability. Based on solubiity and phase studies, oil and surfactant was selected and composition was determined. Microemulsion was spontaneously prepared by mixing ingredients and the physicochemical properties such was investigated. The mean diameters of microemulsion were approximately 90 nm and the system was physically stable at room temperature at least for 3 months. In addition, the in vitro and in vivo performance of microemulsion formulation was evaluated. Aceclofenac was released from microemulsion in acidic aqueous medium, and dissolved amounts of aceclofenac was approximately 30% after 240 min. Skin permeation of aceclofenac from microemulsion formulation was higher than that of cream. Following transdermal application of aceclofenac preparation to delayed onset muscle soreness, serum creatine phosphokinase and lactate dehydrogenase activity was significantly reduced by aceclofenac. Aceclofenac in microemulsion was more potent than cream in the alleviation of muscle pain. Therefore, the microemulsion formulation of aceclofenac appear to be a reasonable transdermal delivery system of the drug with enhanced skin permeability and efficacy for the treatment of muscle damage.

• 한국임상약학회지
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• 제16권1호
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• pp.52-56
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• 2006

Aceclofenac, a nonsteroidal antiinflammatory agent of a phenylacetic acid type, has been used for rheumatoid arthritis and osteoarthrits. Although the metabolic pathway of aceclofenc is relatively well-known in vitro, pharmacokinetic profiles of its three major or metabolites are still unclear in human. The present study was designed to investigate pharmacokinetic profiles of the metabolites of aceclofenac, and to evaluate the bioequivalence of the generic preparation of aceclofenac 100 mg tablet. Blood samples were serially collected for a period of 12 hours following a single oral administration of 100 mg aceclofenac in 20 healthy human volunteers. A simple protein precipitation with acetonitrile was employed to purify those substances from plasma. Aceclofenac, diclofenac, 4'-hydroxyaceclofenac and 4'-hydroxy-diclofenac in heparinized plasma were simultaneously measured with flufenamic acid, an internal standard, using HPLC coupled to a tandem mass spectrometer. Time courses of 4'-hydroxydiclofenac, diclofenac and aceclofenac plasma concentrations were clearly revealed, and the pharmacokinetic properties were analyzed. The 90% confidence intervals for the ratios of test/reference for log-transformed AUC and $C_{max}$ lie within 0.80-1.25.

• Journal of Pharmaceutical Investigation
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• 제29권1호
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• pp.29-36
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• 1999

Aceclofenac is an non-steroidal antiinflammatory drug which has been used in the treatment of rheumatoidal rthritis and osteo-arthritis. In order to decrease the gastric ulcerogenic effects and contol the plasma level of aceclofenac, we have developed the transdermal delivery system of aceclofenac plaster, which were formulated employing matrix polymers of acrylates and penetration-enhancers such as $Lauroglycol^{\circledR}$, $Transcutol^{\circledR}$, oleic acid and linoleic acid. Using Franz diffusion cells mounted with a rat skin, transdermal penetration characteristics of the formulations were evaluated by the HPLC assay of aceclofenac and diclofenac, an active metabolite, in the receptor compartment of pH 7.2 phosphate buffered solution. Skin penetration was increased when the content of aceclofenac increased, showing the flux $(J,\;{\mu}g/cm^2/hr)$ of 0.37 and 2.50 for 2% and 6.75% of the content, respectively. The flux$(J,\;{\mu}g/cm^2/hr)$ from plasters made of $Durotak^{\circledR}$ 87-2074, $Durotak^{\circledR}$ 87-2510 and $Durotak^{\circledR}$ 87-2097 were 2.50, 2.77 and 4.39, respectively. $Durotak^{\circledR}$ 87-2074 showed the lowest penetration due to the carboxylic acid group in the polymer, which might form a strong hydrogen bonding with a secondary amine of aceclofenac. Although both $Durotak^{\circledR}$ 87-2510 and $Durotak^{\circledR}$ 87-2097 are amine-resistant adhesives, $Durotak^{\circledR}$ 872510 showed lower penetration than $Durotak^{\circledR}$ 87-2097 because of the hydroxyl group in $Durotak^{\circledR}$ 87-2510, which might form a weak hydrogen bonding with aceclofenac. These results reveal that the functional group in acrylic polymers would greatly affect the release of aceclofenac from the matrix, which is the rate-limiting step in the penetration of aceclofenac through rat skins. The penetration of aceclofenac from plasters using different penetration-enhancers increased in the following order: Transcutol < linoleic acid < oleic acid. And the flux from the plasters containing oleic acid as a penetrationenhancer was 2.22 times greater than that of creams, which suggest that a newly deveolped aceclofenac plaster could be used in the treatment of rheumatoidal arthritis and osteo-arthritis as an advanced transdermal delivery system.

• 대한물리치료과학회지
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• 제7권2호
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• pp.597-605
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• 2000

There has been several usual ways to cure pain in osteological muscle: use oral medicine or injection, or apply medicine to a sore place. The purpose of this study was to examine, by using thermometer and digital infrared thermographic imaging, how much the permeation of aceclofenac, an anodyne and antiphlogistic, into sore skin brought a change to skin temperature after that was' applied to it. The findings of this study were as below; 1. A cream made of aceclofenac yielded $0.61^{\circ}C$ difference in temperature, but the difference wasn't statistically significant. 2. An aceclofenac to which oleic acid was added went through microemulsion and applied, and there was $0.3^{\circ}C$ change in temperature, the biggest significant difference(P<.05), after approximately 15 minutes passed. 3. An aceclofenac to which labrasol was added went through microemulsion and applied, and there was a growing rise in temperature with the lapse of time. After 30 minutes passed, the final temperature showed $1.25^{\circ}C$ rise, which was a significant change(P<.05). 4. As the temperature was measured by digital infrared thermographic imaging, there was about $3.97^{\circ}C$ fall, the biggest change, which was significant(P<.05). The findings of this study suggested that the application of aceclofenac to sore skin caused a change in skin temperature, as that permeated into it.

• Journal of Pharmaceutical Investigation
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• 제41권4호
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• pp.217-225
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• 2011

The aim of this work was to prepare porous osmotic pump tablets for controlled delivery of Aceclofenac. Aceclofenac solid dispersion was prepared to improve the solubility by using the drug - carrier (Mannitol) ratio of 1:1. The osmotic pump tablets were prepared using the solid dispersed product of Aceclofenac. The formulation contains potassium chloride as osmotic agent, cellulose acetate as semipermeable membrane, poly ethylene glycol (PEG 4000) as pore former and sodium lauryl sulphate (SLS) as solubility enhancer. The formulations were designed by the general factors such as osmotic agent and pore former. All formulations were evaluated for various physical parameters and, the in vitro release studies were conducted as per USP. The drug release kinetic studies such as zero order, first order, and Higuchi and Korsmeyer peppas were determined and compared. All the formulations gave more controlled release compared to the marketed tablet studied. Numerical optimization techniques were applied to found out the best formulation by considering the parameter of in vitro drug release kinetics and dissolution profile standards. It was concluded that the porous osmotic pump tablets (F7) composed of Aceclofenac solid dispersion/Potassium chloride/Lactose/Sodium lauryl sulphate/Magnesium Stearate (400/40/95/10/5, mg/tab) and coating composition with Cellulose acetate/ PEG 4000 (60/40 %w/w) is the most satisfactory formulation. The porous osmotic pump tablets provide prolonged, controlled, and gastrointestinal environment-independent drug release.

• Archives of Pharmacal Research
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• 제28권9호
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• pp.1097-1102
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• 2005

An O/W microemulsion system was developed to enhance the skin permeability of ace-clofenac. Of the oils studied, Labrafil? M 1944 CS was chosen as the oil phase: of the microemulson, as it showed a good solubilizing capacity. Pseudo-ternary phase diagrams were constructed to obtain the concentration range of oil, surfactant, Cremophor ELP, and co-surfactant, ethanol, for micoemulsion formation. Eight different formulations with various values of oil of $6-30\%$, water of $0-80\%$, and the mixture of surfactant and co-surfactant (at the ratio of 2) of $14-70\%$. The in vitro transdermal permeability of aceclofenac from the microemulsions was evaluated using Franz diffusion cells mounted with rat skin. The level of aceclofenac permeated was analyzed by HPLC and the droplet size' of the microemulsions was characterized using a Zetasizer Nano-ZS. Terpenes were added to the microemulsions at a level of $5\%$, and their effects on the skin permeation of aceclofenac were investigated. The mean diameters of the microemulsions ranged between approximately $10\~100nm$, and the skin permeability of the aceclofenac incorporated into the microemulsion systems was 5-fold higher than that of the ethanol vehicle. Of the various terpenes added, limonene had the best enhancing ability. These results indicate that the microemulsion pystem studied is a promising tool for the percutaneous delivery of aceclofenac.

• Journal of Dental Anesthesia and Pain Medicine
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• 제22권1호
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• pp.29-37
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• 2022

Background: Pain, edema, and trismus are predictable sequelae for surgical extraction of impacted mandibular third molars (M3M). The present study aimed to compare the anti-phlogistic potential of bromelain and aceclofenac in the reduction of post-surgical sequalae in the extraction of impacted M3M. Method: A randomized controlled, triple-blinded clinical study included 72 patients scheduled for surgical removal of impacted M3M under local anesthesia. Randomization was performed and subjects were equally allocated to groups A (control) and B (study), who intended to receive aceclofenac and bromelain, respectively. The primary outcome variables were pain, edema, and trismus evaluated on postoperative days 2 and 7 and compared with baseline values. The secondary variables evaluated were the quantity of rescue analgesics required and the frequency of adverse effects in both groups for 7 postoperative (PO) days. Data were analyzed with a level of significance of P < 0.05. Results: Group B demonstrated a significant decrease in the severity of edema and trismus compared to group A on both PO days 2 and 7 (P < 0.001). Bromelain demonstrated similar analgesic efficacy with an insignificant difference compared to aceclofenac (P > 0.05). Conclusion: The present study showed that the efficacy of bromelain was comparable to that of aceclofenac in reducing inflammatory complications following surgical removal of impacted M3M. Bromelain can be considered a safe and potent alternative to routinely used aceclofenac when addressing inflammatory outcomes after surgery.

• 폴리머
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• 제33권6호
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• pp.596-601
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• 2009

아세클로페낙은 높은 결정성을 갖는 난용성 약물이다. 이러한 난용성 약물의 용해도를 증진시키기 위해서 고체분산법을 바탕으로 한 분무건조기를 이용하여 미립구를 제조하였다. PVP-K30을 수용성 담체로 사용하였고 폴록사머는 계면활성화제로 사용하였다. 제조된 아세클로페낙 고체분산체의 특성을 SEM, DSC, XRD 그리고 FT-IR을 이용하여 확인하였다. SEM, DSC, XRD을 통하여 아세클로페낙 고체분산체가 무정형임을 알 수 있었고 FT-IR을 통하여 아세클로페낙과 PVP-K30간에 수소결합을 통해 염을 형성하고 있다는 것을 확인할 수 있었다. 제조된 미립구는 pH 6.8에서 방출을 실시하였으며 시판제인 $Airtal^{(R)}$과 용출률을 비교하였으며 분무건조를 통해 제조한 미립구가 시판제인 $Airtal^{(R)}$ 보다 용출률이 크다는 것을 확인하였다.

• 한국임상약학회지
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• 제12권1호
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• pp.22-28
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• 2002

Aceclofenac, 2-[(2',6'-dichlorphenyl)amino]phenylacetoxiacetic acid, is a new nonsteroidal anti-inflammatory drug that belongs to the family of phenylacetic acids. It shows good tolerance and potent analgesic/antiinflammatory properties, and acts on cartilaginous chondriocytes, stimulating their repair mechanism. The purpose of the present study was to evaluate the bioequivalence of two aceclofenac products, $Airtal^{TM}$ tablet (Daewoong Pharmaceutical Co.) and $Acer^{TM}$ capsule (Kyungdong Pharmaceutical Co.), according to the guideliner of Korea Food and Drug Administration (KFDA). The aceclofenac release from the two aceclofenac products in vitro was tested using KP VII Apparatus II method at pH 7.8 dissolution media. Sixteen normal male volunteers, $23.13\pm2.03$ years in age and $66.33\pm7.08$ kg in body weight, were divided into two groups and a randomized $2\times2$ cross-over study was employed. After one tablet or capsule containing 100 mg of aceclofenac was orally administered, blood was taken at predetermined time intervals and the concentrations of aceclofenac in serum were determined using HPLC with UV detector. The dissolution profiles of the two aceclofenac products were very similar at pH 7.8 dissolution media. The pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_max$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two products were $6.50\%,\;-1.06\%\;and\;11.96\%$ respectively, when calculated against the $Airtal^{TM}$ tablet. The powers $(1-\beta)\;for\;AUC_t,\;C_{max}\;were\;89.82\%\;and\;82.84\%$, respectively. Minimum detectable differences $(\Delta)\;at\;\alpha=0.05\;and\;1-\beta=0.8$ were less than $20\%\;(e.g.,\;17.51\%\;and\;19.30\%\;for\;AUC_t,\;C_{max}$, ). The $90\%$ confidence intervals were within $\pm20\%\;(e.g.,\;-3.73\%\sim16.73\%\;and\;-12.34\%\sim10.22\%\;for\;AUC_t,\;C_{max},\;respectively)$. Two parameters met the criteria of KFDA for bioequivalence, indicating that $Acer^{TM}$ capsule is bioequivalent to $Airtal^{TM}$ tablet.

• Biomolecules & Therapeutics
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• 제6권4호
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• pp.423-428
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• 1998

Aceclofenac is an orally effective non-steroidal anti-inflammatory agent of the phenylacetic acid derivative. Bioequivalence study of two aceclofenac preparations, the test drug (Senafe $n_{R}$: Daewon Phar-maceutical Company) and the reference drug (Airta $l_{R}$: Daewoong Pharmaceutical Company), was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Sixteen healthy male volunteers, 24$\pm$4 years old and 63.9$\pm$6.9 kg of body weight in average, were divided randomly into two groups and administered the drug orally at the dose of 100 mg as aceclofenac in a 2$\times$2 crossover study. Plasma concentrations of aceclofenac were monitored by HPLC method for 12 hr after administration. AU $Co_{-12h}$ (area under the plasma concentration-time curve from initial to 12 hr) was calculated by the linear trapezoidal method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{msx}$) were compiled directly from the plasma drug concentration-time data. Student's t-test indicated no significant differences between the formulations in these parameters. Analysis of variance (ANOVA) revealed that there are no differences in AU $Co_{12h}$, $C_{max}$ and $T_{max}$ between the formulations. The apparent differences between the formulations were far less than 20% (e.g., 0.25, 0.01 and 7.32 for AU $Co_{-12h}$, $C_{max}$. and $T_{max}$, respectively). Minimum detectable differences (%) between the formulations at $\alpha$=0.05 and 1-$\beta$=0.8 were less than 20% (e.g., 14.65, 12.47 and 15.46 for AU $Co_{-l2h}$, $C_{max}$ and $T_{max}$, respectively). The 90% confidence intervals for these parameters were also within $\pm$ 20% (e.g.,-10.19~10.68, -8.87~8.89 and -3.69~ 18.33 for AU $Co_{-12h}$, $C_{msx}$ and $T_{max}$, respectively). These results satisfy the bioequivalence criteria of KFDA guidelines, indicating that two formulations of aceclofenac are bioequivalent.quivalent.ivalent.ent.t.ent.