• Microbiology and Biotechnology Letters
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• v.28 no.4
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• pp.223-227
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• 2000

A novel two-step acetone treatment method was developed to enhance the enantioselectivity of Candida rugosa lipase (CRL) toward the hydrolysis of racemic naproxen methyl ester. The acetone-teated CRL was considerably more enantioselective than the crude CRL, yielding an enantiomeric excess of 98~100%. The crude and acetone-treated CRLs were subjected to anion exchange chromatography, and their chromatography profiles were compared. In consequence, both chromatography profiles were found to be almost identical, resulting in two separate lipase peaks (lipase A and B). The lipase B, which is known to be less enantioselective, was treated with acetone using a two-step treatment method. The enantioselectivity of acetone-treated lipase B was dramatically increased, yielding an enantiomeric excess of 99%.

• Journal of Pharmaceutical Investigation
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• v.29 no.4
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• pp.343-348
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• 1999

The purpose of this study is to prepare the controlled release adhesive patch containing naproxen. Pressuresensitive adhesive (PSA)-type patch was fabricated by casting of polyisobutylene (PIE.) and mineral oil in toluene. Membrane-controlled release (MCR)-type patch was prepared by the attachment of the controlled release membrane on the PSAtype patch. The membrane was mainly composed of Eudragit, polyethylene glycol(PEG) and glycerin. The drug release profile and skin permeation test with various patches were evaluated in vitro. The release of naproxen from PIE-based PSAtype patch with various loading doses fitted Higuchi's diffusion equation. However, the permeation of naproxen through hairless mouse skin from PSA-type patch followed zero-order kinetics. In MCR-type patch, thickness of controlled release membrane affected on the drug release rate highly. In the composition of membrane, the release rate was decreased as the ratio of Eudragit increased. The drug release from the MCR-type patch followed zero order kinetics. The permeation of naproxen through hairless mouse skin from MCR-type patch showed lag time for the intial release period and didn't fit the zero-order kinetics

• YAKHAK HOEJI
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• v.49 no.1
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• pp.1-5
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• 2005

Near-infrared (NIR) spectroscopy has been widely applied in various field, since it is nondestructive and no sample preparation is required. In this paper, NIR spectroscopy was used for the determination of naproxen in a commercial pharmaceutical preparation. NIR spectroscopy was used to determine the content of naproxen in intact naproxen tablets containing 250 mg ($65.8\%$ nominal concentration) by collecting NIR spectra in the range of $1100{\sim}1750nm$. The laboratory-made samples had $46.1{\sim}85.5\%$ nominal naproxen concentration. The measurements were made by reflection using a fiber-optic probe and calibration was carried out by partial least square regression (PLSR). Model validation was performed by randomly splitting the data set into calibration and validation data set (63 samples as a calibration data set and 42 samples as a validation data set). The developed NIR calibration gave results comparable to the known values of tablets in a laboratorial manufacturing process with standard error of calibration (SEC) and standard error of prediction (SEP) of $1.06\%\;and\;1.04\%$, respectively. The NIR method showed good accuracy and repeatability. NIR spectroscopic determination in intact tablets allowed the potential use of real time monitoring for a running production process.

• Journal of the Korean Chemical Society
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• v.58 no.2
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• pp.179-185
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• 2014

Commercial (S)-naproxen was racemized under strong basic condition. After checking the peak position of (R)- and (S)-naproxen by analysis the recemized naproxen, optical purity of 19 commercialized naproxens sold in 2013 in Korea were examined by chiral HPLC. The Chiralcel OD-H column, ChiralHyun-LE(S)-1 column and LUX-Cellulose-1 column were used as chiral stationary phases and the mixed eluent of hexane:isopropanol:acetic acid as 100:1:0.1 was used as a mobile phase with a flow rate of 1.0 mL/min. Each data was obtained from an average value of at least three different experiments for each sample and the relative standard deviation of them appeared very small. The average optical purity values obtained from three different chiral columns were very similar and the total average optical purity value (99.32%) of nineteen commercialized naproxens used in this study were larger than those of three years ago (98.17%).

• Journal of Microbiology and Biotechnology
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• v.26 no.8
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• pp.1392-1397
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• 2016

Curcumin is a polyphenol derived from the plant Curcuma longa, which is used for the treatment of diseases associated with oxidative stress and inflammation. The present study was undertaken to determine the protective effect of curcumin against naproxen-induced gastric antral ulcerations in rats. Different doses (10, 50, and 100 mg/kg) of curcumin or vehicle (curcumin, 0 mg/kg) were pretreated for 3 days by oral gavage, and then gastric mucosal lesions were caused by 80 mg/kg naproxen applied for 3 days. Curcumin significantly inhibited the naproxen-induced gastric antral ulcer area and lipid peroxidation in a dose-dependent manner. In addition, curcumin markedly increased activities of radical scavenging enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase in a dose-dependent manner. Specifically, 100 mg/kg curcumin completely protected the gastric mucosa against the loss in the enzyme, resulting in a drastic increase of activities of radical scavenging enzymes up to more than the level of untreated normal rats. Histological examination obviously showed that curcumin prevents naproxen-induced gastric antral ulceration as a result of direct protection of the gastric mucosa. These results suggest that curcumin blocks naproxen-induced gastric antral ulcerations through prevention of lipid peroxidation and activation of radical scavenging enzymes, and it may offer a potential remedy of gastric antral ulcerations.

• Archives of Pharmacal Research
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• v.20 no.5
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• pp.414-419
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• 1997

Gastrointestinal irritation is the most frequent adverse effect in patients chronically taking nonsteroidal antiinflammatory drugs (NSAIDs) for the treatment of arthritic conditions. Gastroprotective effect of DA-9601, a new antiulcer agent from Artemisiae Herba extract, against NSAID was evaluated in a rat model of arthritis that is similar in many aspects to human rheumatoid arthritis. Daily oral dosing of naproxen (30 mg/kg), one of the most commonly used NSAID, induced apparent gastric lesions as well as a significant decrease in mucosal prostagiandin $E_2;(PGE_2)$ and prostagiandin F_${1{\alpha}}$$(PGF_{1{\alpha}})$ levels. Coadministration of DA-9601 prevents naproxen-induced mucosal injury and depletion of prostaglandins, in a dose-related manner. DA-9601 did not alter the antiinflammatory or analgesic effect of naproxen. The present results suggest that DA-9601 may be useful as a mucoprotectant against NSAIDs in clinical practice.

• Journal of Microbiology and Biotechnology
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• v.19 no.12
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• pp.1596-1602
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• 2009

A lipase-catalyzed esterification reaction of (S)-naproxen ethyl ester by CALB (Candida antarctica lipase B) enzyme was performed in supercritical carbon dioxide. Experiments were performed in a high-pressure cell for 10 h at a stirring rate of 150 rpm over a temperature range of 313.15 to 333.15 K and a pressure range of 50 to 175 bar. The productivity of (S)-naproxen ethyl ester was compared with the result in ambient condition. The total reaction time and conversion yields of the catalyzed reaction in supercritical carbon dioxide were compared with those at ambient temperature and pressure. The experimental results show that the conversion and reaction rate were significantly improved at critical condition. The maximum conversion yield was 9.9% (216 h) at ambient condition and 68.9% (3 h) in supercritical state. The effects of varying amounts of enzyme and water were also examined and the optimum condition was found (7 g of enzyme and 2% water content).

• Analytical Science and Technology
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• v.37 no.2
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• pp.114-122
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• 2024

A transmission Raman spectroscopy-based quantitative model, which can analyze the content of a drug product containing naproxen sodium as its active pharmaceutical ingredient (API), was developed. Compared with the existing analytical method, i.e., high-performance liquid chromatography (HPLC), Raman spectroscopy exhibits high test efficiency owing to its shorter sample pre-treatment and measurement time. Raman spectroscopy is environmentally friendly since samples can be tested rapidly via a nondestructive method without sample preparation using solvent. Through this analysis method, rapid on-site analysis was possible and it could prevent the production of defective tablets with potency problems. The developed method was applied to the assays of the naproxen sodium of coated tablets that were manufactured in commercial scale and the content of naproxen sodium was accurately predicted by Raman spectroscopy and compared with the reference analytical method such as HPLC. The method validation of the new approach was also performed. Further, the specificity, linearity, accuracy, precision, and robustness tests were conducted, and all the results were within the criteria. The standard error of cross-validation and standard error of prediction values were determined as 0.949 % and 0.724 %, respectively.

• Archives of Pharmacal Research
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• v.16 no.1
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• pp.50-56
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• 1993

The microencapsulation of sodium naproxen with Eudragit. RS was studied by coacrtvation/phase separation process using Span 80 in mineral oil/acetone system. Various factors which affect the mciroencapsulation, e.g., stirring speed, and surfactant concentraction, Eudagit RS concentration and loading drug amounts were examined. For the evaluation of the prepared microcapsules, release rate, particle size distribution and surface appearance as well as in vivo test were carried out. The addition of n-hexane and freezing of microcapsules accelerated the hardening of microcapsules. The optimum concentration of Span 80 ti prepare the smallest microcapsules was the same value with the CMC of Span 80 in solvent system. When 1.5% (w/w) Span 80 was used, the smallest microcapsules were formed $(30.02\pm5.05\mu$ in diameter) belonging to the powder category showing smooth, round and uniform surface. The release of sodium naproxen was retarded by microencapsulation with Eudragit RS. The Eudragit RS microcapsules showed significantly increased AUC and MRT and deceased Cl/F in rabbits.

• Archives of Pharmacal Research
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• v.13 no.2
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• pp.166-173
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• 1990

The structure of the anti-inflammatory agent, naproxen sodium was determined by single crystal X-ray diffraction analysis. Crystal of the compound, which was recrystallized from methanol solution, is nomoclinic, space group $P2_1$ with a = 21. 177(6), b = 5.785(2), c = 5.443(2) $\AA, \beta$ = 91.41(3)$\{\circ}$ and Z = 2. The calculated density is 1.346; the observed value is nements based on 1093 reflections ($F\geq3\sigma$(F)) gave the final R value of 0.043. There are of one water per one compound molecule in the crystal. The carboxyl group of the molecule is nearly perpendicular to the naphthalene ring. The molecules are arranged along with the screw axis, and stabilized by five 0...Na type interactions. The molecule retains nearly same dimensions and similar conformation compared to its parent compound, naproxen, except for the torsion angles around C(5)-C(11) bond.