• YAKHAK HOEJI
• /
• v.44 no.6
• /
• pp.595-600
• /
• 2000

Transdermal delivery of ketorolac tromethamine, a potent non-narcotic analgesic, through human cadaver skin was investigated in vitro. A mixture of ethanol/water (40/60) containing 0, 1, 3, 5, and 8 (w/v)% L-menthol were used as a vehicle and penetration enhancer respectively. The permeation of ketorolac through human cadaver skin from saturated drug solution was evaluated at $37^{\circ}C$ with modified Franz diffusion cell. The in vitro skin flux and lag time were $1.23\;{\pm}\;0.11\;{\mu}g/cm^2{\cdot}hr$ and $5.56\;{\pm}\;0.34\;hr$, respectively. The cumulative amount of penetrated ketorolac containing L-menthol in ethanol/water (40/60) binary system was increased by the following order; 3%, 5%, 8%, 1%, 0%, and the lag time was decresed by the following order; 3%, 5%, 8%, 0%, 1%. The results suggested that a potential use of 3% L-methol is an effective penetration enhancer of ketorolac tromethamine through the human cadaver skin.

• Archives of Pharmacal Research
• /
• v.19 no.6
• /
• pp.529-534
• /
• 1996

A high-performance liquid chromatographic (HPLC) assay has been developed for the determination of ketorolac in human serum using a new extraction method with a good recovery. Human serum samples (1.0 ml) spiked with known concentrations of ketorolac tromethamine and 10${\mu}g$ of ketoprofen as the internal standard (IS) were acidified with 200${\mu}l$ of 1 N HCl and extracted with 7 ml of n-hexane-ether (7:3 v/v). Extracts were centrifuged and organic layer was back-extracted with 400${\mu}l$ of 0.1% tromethamine solution. Twenty .mu.l of centrifuged aqueous layer was injected onto a reversed-phase octyl column and eluted with a mixture of acetonitrile, water, methanol, and triethylamine [35:55:10:0.1 (v/v), pH 3.0] at a flow rate of 1.0 ml/min. Ultraviolet detection of ketorolac and IS was carried out at 300 nm. The calibration curve obtained using peak area ratios showed a good linearity (in concentration range 10-150 ng/ml $r^2$=O.9944; in range 50-2000 ng/ml, r$^{2}$=0.9998). The mean intra-day accuracy and precision for this HPLC method were found to be 3.6 and 3.7%, respectively. The mean inter-day accuracy and precision were found to be 4.0 and 3.7%, respectively, in the concentration range 50-2000 ng/ml. The recovery of ketorolac from serum was 92.0 $({\pm}5.7)$ % at the concentration of 100 ng/ml. This method proved to be readily applicable to the assay of ketorolac in human serum.

• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.234.1-234.1
• /
• 2003

The effects of vehicles and penetration enhancers on the in vitro permeation of ketorolac tromethamine (KT) across excised hairless mouse skins were investigated. Among pure vehicles examined, propylene glycol monolaurate (PGML) showed the highest permeation flux, which was 94.3${\pm}$17.3 mg/cm$^2$/hr. Even though propylene glycol monocaprylate (PGMC) alone did not show high permeation rate, the skin permeability of DT was markedly increased by the addition of diethylene glycol monoethyl ether (DGME); the enhancement factors were 19.0 and 17.1 at 20 and 40% of DGME, respectively. (omitted)

• Journal of dental hygiene science
• /
• v.10 no.2
• /
• pp.79-83
• /
• 2010

This study manufactured hydrogel, which was contained NSAIDs(non-steroidal anti-inflammatory drugs) Ketorolac tromethamine and hydrolyzed products of gardeniae fructus extract, and experimented viscosity, surface tension, tensile strength and bio-adhesiveness by using hairless mouse. Thus, it was performed in expectation for being probably able to develop as effective auxiliary agent of periodontal disease after non-surgical or surgical periodontal treatment. As a result, the following conclusions were obtained. 1. Out of KGE and KGH gel materials, the content of ketorolac tromethamine was 1.02~0.97%. The content of geniposide was 0.34% in KGE gel A and C. However, it got lower to 0.11% in KGH gel B and D. The content of genipin wasn't shown in KGE gel A and C, but was shown with 0.13% in KGH gel B and D. 2. As for viscosity according to temperature in gel material, the gel, which used independently Carbopol 940 as gel inoculant, maintained the higher viscosity than the gel, which added Poloxamer 407. The surface tension in each material showed 34.77~40.58 dyne/cm at 37. As for tensile strength in material, KGH gel B was shown the higher tensile strength in about 3.5 times compared to the control group. 3. As for bio-adhesiveness, the back-skin upper part(epidermis) and abdomen skin were shown to be 50.62 N in KGH gel B, thereby having indicated higher value in about 5 times compared to control group. The back-skin lower part(dermis) and abdomen skin were shown to be 35.93 N in KGH gel B, thereby having indicated higher value in about 3.5 times compared to control group.

• The Korean Journal of Pain
• /
• v.8 no.1
• /
• pp.37-42
• /
• 1995

The intermittent injection of analgesics is a inadquate method for postoperative pain control. Recently a non-electroic, disposable and portable infusor (Boxter Two Day $Infusor^R$) has been developed which can deliver analgesics with 2 ml/h speed continuousely. The present study examined the effects of three methods of pain management on recovery in 306 patients undergoing elective surgery in Wonkwang University Hospital. Group 1 (n=106) received i.m. $Valentac^R$ on a PRN basis. Group 2 (n=100), initial 2 mg of bolus morphine was followed by 48 mg of continuous infusion. Group 3 (n=100), initial 2 mg of morphine followed by morphine 18 mg-ketorolac 120 mg. We evaluated an analgesic efficacy with NRS (numerical rating scale) at 12, 24, 36, 48, 60 and 72 hours after the operation. The side effects (nausea, vomiting, pruritus, sedation and respiratory depression) were evaluated. In group 1, we asked major concern before operation and efficacy of pain control with pain severity (no pain, mild pain, moderate pain, sever pain). The results were as follows: 1) Major concern before operation is pain (40%). 2) 53% of patients suffered pain in group 1. 3) Morphine and morphine-ketorolac infusion groups were superior to the i. m. ($Valentac^R$) group with respect to postoperative analgesia. 4) In group 3 (morphine-ketorolac), there was no pruritus and mild nausea and vomiting.

• Journal of Pharmaceutical Investigation
• /
• v.33 no.1
• /
• pp.21-28
• /
• 2003

Ketorolac tromethamine(KT) is a nonsteroidal agent with potent analgesic and moderate anti-inflammatory activity. The lipid-water partition coefficient of KT was evaluated and KT gel was formulated as a gel containing different pH, different concentrations of polymer (poloxamer 407, carbopol 941), propylene glycol, ethanol and various enhancers. The resulting KT gels were evaluated with respect to their viscosity, in vitro drug permeation rate through hairless mouse skin and stability. In n-octanol and chloroform, the lipid-water partition coefficient of KT was the highest at pH 4 phosphate buffer. The apparent viscosity of KT gel increased with an increase in gel pH, polymer and enhancer concentration. But the apparent viscosity of KT gel decreased with an increase in ethanol concentration. The permeation rate of KT through hairless mouse skin from gels different pH was maximum at pH 4 which is close to KT $pK_{a}$ 3.54. The permeation rate decreased with an increase in polymer, propylene glycol concentration. But the permeation rate increased with an increase in ethanol. The increase of drug concentration from 1 to 3% induced linear increase in permeation rate. The best enhancer was the combination of $Labrasol^{\circledR},\;Transcutol^{\circledR}$, oleic acid and l-menthol. In the accelerated stability test(25, 40 and $50{\circ}C$), pH 5 gel was most stable and pH 4 gel was most unstable for 90 days.

• Journal of Pharmaceutical Investigation
• /
• v.29 no.1
• /
• pp.67-72
• /
• 1999

A bioequivalence study of the $Kerola^{\circledR}$ intramuscular injections (Dongkwang Pharmaceutical Co., Korea) to the $Tarasyn^{\circledR}$ intramuscular injections (Roche Co., Korea), formulations of ketorolac tromethamine (KTR), was conducted. Sixteen healthy Korean male subjects were received each formulation at the dose of 30 mg as KTR in a $2{\times}2$ crossover study. There was an one-week washout period between the doses. Plasma concentrations of KTR were monitored by a HPLC method. AUC was calculated by the linear trapezoidal method. $C_{max}$ and $T_{max}$ were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed that there are no differences in AUC, $C_{max}$ and $T_{max}$ between the formulations. The differences between the formulations in these parameters were all far less than 20% (i.e., 3.65, 2.59 and 4.35% for AUC, $C_{max}$ and $T_{max}$ respectively). Minimum detectable differences (%) at ${\alpha}=0.1$ and $1-{\beta}=0.8$ were 12.87, 13.44, 20.62%, for AUC, $C_{max}$ and $T_{max}$, respectively. The 90% confidence intervals for these parameters were also within 20%. These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 1998-86). Therefore, these results indicate that the two formulations of KTR are bioequivalent.

• Journal of dental hygiene science
• /
• v.5 no.3
• /
• pp.113-117
• /
• 2005

After producing 4 kinds of hydrogel materials by mixing the composite preparation in Gardeniae Fructus extracts with ketorolac tromethamine, which is NSAIDs (nonsteroidal anti-inflammatory drugs), through the experiment of measurement in the tensile strength, in the skin permeation, and in the periodontal-pocket reduction rate, the following conclusions were obtained. 1. The tensile strength of a drug indicated the tensile strength 3.5-fold higher compared to the control group, in KGH gel B. 2. The skin-permeation volume in ketorolac tromethamine was highest with $105.62{\mu}m/cm^2$ in KGH gel B for 8 hours, and the permeation volume in geniposide was relatively high with $73.8{\mu}m/cm^2$ in KGE gel A, but the permeation volume in genipin, which is the hydrolysis, represented the highest permeation amount with $50.17{\mu}m/cm^2$ in KGH gel B. 3. In terms of the periodontal-pocket reduction rate, after 4 weeks, KGE gel A showed the falling rate of 23.85% compared to the control group, but did not indicate the significant difference, and KGH gel B represented the reduction rate of 29.46% compared to the control group, thus it indicated the significantly treatment effect.

• Journal of Pharmaceutical Investigation
• /
• v.30 no.4
• /
• pp.241-246
• /
• 2000

To develop a sustained-release preparation containing ketorolac tromethamine, two sustained-release pellet formulations were evaluated with a pharmacokinetic study as compared with a conventional commercial tablets (10 mg $Tarasyn^{TM}$, Roche Korea Ltd.). Two sustained-release formulations were as follows; formulation A was composed of an inner layer containing 75% of drug coated with $Eudragit^{TM}$ RS 100 membrane and an outer layer containing 25% of drug mixed with $Eudragit^{TM}$ NE30D, and formulation B was composed of only an inner layer containing 100% of drug coated with $Eudragit^{TM}$ RS 100 membrane. The dissolution test was performed for two formulations. In case of conventional tablets, 2.5 mg of drug per a dose was administered orally into male Albino rabbit (2.0-2.3 kg of body weight) 3 times at intervals of 4 hours. In case of two sustained formulations, 7.5 mg of drug was administered once orally. Blood samples were withdrawn periodically after the administration, and the blood concentration was determined by HPLC. The conventional tablets showed very high peak-trough fluctuation between administered doses, but two sustained formulations showed less fluctuation. Formulation A with the loading dose showed the time to reach minimum effective concentration (MEC) i.e. the onset time was less than 20 min, while Formulation B had more than 1 hr of the onset time. Formulation A had the more constant plasma level than formulation B. However, formulation B had a time lag, so the plasma level was less than MEC for an initial period of 1 hr. In formulation A, the plasma level was maintained within the therapeutic window $(0.3-5\;{\mu}g/ml)$ for a long period. Formulation A was thought to be an ideal sustained-release formulation for ketorolac tromethamine oral delivery system.

• Korean Journal of Head & Neck Oncology
• /
• v.16 no.2
• /
• pp.182-186
• /
• 2000

The reduction of the postoperative wound pain has been a concern in recent surgery, especially in various types of minimally-invasive surgeries. This study was performed to evaluate the postoperative analgesic effect of the preincisional local anesthesia with the mixture of ketorolac(Tarasyn) and bupivacaine to the surgical site in minimally-invasive thyroid surgeries. Of 491 patients who were scheduled for minimally-invasive thyroid surgeries between October 1999 and July 2000, 244 were randomly assigned to receive a mixture of ketorolac tromethamine 15mg(0.5ml) and 0.25% bupivacaine 3ml via surgical site infiltration 3 minutes prior to the skin incision. The outcomes of these patients were compared to those of the 247 controls. Total number of patients in need of post-operative analgesic requirements(n=39, 16.0%), total dose of postoperative analgesics used($19.6{\pm}8.4mg$ of ketorolac) and Visual Analogue Pain Score(VAS, $2.6{\pm}1.2$) of the preincisional local anesthesia group were significantly lower than those of the control group(p<0.05). The mean postoperative hospital stay was $1.6{\pm}0.4$ days for the preincisional local anesthesia group versus $1.9{\pm}0.7$ days for the control group. The preincisional local infiltration of ketorolac and bupivacaine in the minimally invasive thyroidectomies reduces postoperative wound pain thus would be more beneficial to the patients.