• Journal of Pharmaceutical Investigation
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• 제28권3호
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• pp.185-191
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• 1998

A bioequivalence study of the Loxipen tablets (Dae Wha Pharmaceutical Co., Korea) to the Loxonin tablets (Dong Hwa Pharmaceutical Co., Korea), formulations of sodium loxoprofen anhydrous 60 mg, was conducted. Sixteen healthy Korean male subjects received each formulation at the dose of 60 mg as sodium loxoprofen anhydrous in a $2{\times}2$ crossover study. There was a 2-week washout period between the dose. Plasma concentrations of loxoprofen were monitored by an HPLC method for over a period of 6 h after each administration. AUC (area under the plasma concentration-time curve from time zero to infinity) was calculated by the linear trapezoidal and extrapolation method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ $(time\;to\;reach\;C_{max})$ 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 apparent differences between the formulations in these parameters were all far less than 20% (i.e., 5.88, 7.81 and 6.09% for AUC, $C_{max}$ and $T_{max}$, respectively). Minimum detectable differences (%) at ${\alpha}=0.1$ and $1-{\beta}=0.8$ were all less than 20% difference in these parameters between the formulations were all over 0.8 (i.e., 15.81, 13.13 and 19.85 for AUC, $C_{max}$ and $T_{max}$, respectively). The 90% confidence intervals for these parameters were also within ${\pm}20%$ (i.e., $-16.52{\sim}4.77$, $-16.65{\sim}1,02$ and $-19.45{\sim}7.28%$ for AUC, $C_{max}$ and $T_{max}$, respectively). These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 98-51). Therefore, these results indicate that the 2 formulations of loxoprofen are bioequivalent and, thus, may be prescribed interchangeably.

• 한국산학기술학회논문지
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• 제10권11호
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• pp.3494-3499
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• 2009

소화성 궤양의 치료에 일반적으로 병용되어 사용되는 소염진통제인 록소프로펜 또는 알칼리화제인 탄산수소나트륨을 함유한 수용액 중에서 소화성 궤양의 치료에 사용되는 오메프라졸의 안정성에 대한 영향이 실온상태에서 실험하였다. 록소프로펜과 탄산수소나트륨 각각 60 mg을 오메프라졸(600 ${\mu}g$/ml) 용액에 혼합한 후 그 용액을 실온 상태로 80시간 보존하면서 그 분해정도를 원래의 오메프라졸의 농도와 비교하여 각각의 소실 농도를 산출하였다. 오메프라졸의 농도와 크로마토그램의 면적비는 5 - 160 ${\mu}g$/ml 농도에서 상호 직선성을 나타내었고 상대 표준 편차는 3.05 %이하로서 분석이 제대로 이루어졌음을 확인할 수 있었으며 함유 약물과 시간에 따른 오메프라졸의 분해 양상은 가상의 일차 직선 속도식을 나타내는 것을 알 수 있었다. 결론적으로 오메프라졸은 탄산수소나트륨 또는 록소프로 펜과의 병용 투여에 의해 그 안정성이 영향을 받을 수 있다는 것을 확인할 수 있었다.

• Biomolecules & Therapeutics
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• 제9권4호
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• pp.298-306
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• 2001

To develop a novel transdermal delivery system of loxoprofen (LP), a potent antiinflammatory and analgesic agent, the effects of vehicle composition and drug loading dose on the skin permeation property were investigated. And in vivo skin absorption property studied by analysing the $C_{max}$ and AUC was investigated after applying the developed plaster systems on rabbit back skin. Addition of isopropyl myristate (IPM) and IPM-diethylene glycol monoethyl ether (DGME) cosolvent in the plaster showed higher permeation rates than those from propylene glycol laurate-DGME cosolvent systems. As the concentration of LP in the plaster increased from 0.56 mg/$\textrm{cm}^2$ to 1.19 mg/$\textrm{cm}^2$, the drug release and skin permeation rates increased linearly. At loading dose of 1.19 mg/$\textrm{cm}^2$, the flux reached 35.6 $\mu$g/$\textrm{cm}^2$/hr. New LP plasters showed a good adhesive property onto skin, and showed no crystal formation. The AU $C_{0-24hr}$ and $C_{max}$ after dermal application of LP plaster (60 mg/70 $\textrm{cm}^2$) were found to be 6951$\pm$230 ng.hr/ml and 400$\pm$44 ng/ml, respectively. And the plasma concentration maintained above 300 ng/ml up to 24 hr period. In the carrageenan-induced rat paw edema test, LP plaster showed similar inhibition rate with marketed ketoprofen (Ketoto $p^{R}$) plaster.aster.r.

• Journal of Pharmaceutical Investigation
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• 제31권4호
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• pp.217-224
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• 2001

To develop a novel transdermal delivery system of loxoprofen (LP), a potent antiinflammatory and analgesic agent, the effects of various vehicles and penetration enhancers on the skin permeation of LP from solution formulations were investigated. The permeation rate of LP through excised guinea pig skin was measured using a side-by-side permeation system at $32^{\circ}C$. The solubilities of LP in various vehicles were determined by the equilibrium solubility method, and partition coefficients $(P_c)$ were determined. The solubility of LP increased in the rank order of water & isopropyl myristate (IPM) & glyceryl dicaprylate/dicaprate & propylene glycol dicaprylate/caprate & propylene glycol laurate (PGL) & polyethylene glycol 400 & diethylene glycol monoethyl ether (DGME) & ethanol. n-Octanol-water $P_c$ value was 15.5. Among pure vehicles tested, IPM and PGL showed highest fluxes of $89.9{\pm}5.0$ and $45.4{\pm}0.3\;{\mu}g/cm^2/hr$ from saturated solutions, respectively. However, it was not possible to demonstrate any correlation between the solubility of LP and its permeation rate, indicating the change in the barrier property of the skin and/or carrier mechanisms by vehicles tested. The addition of DGME to IPM or PGL markedly increased the solubility of LP, but the permeation rate did not decrease when the concentration of DGME in the cosolvent was increased upto 40%. The addition of linoleic acid (3%) in the cosolvent slightly increased the permeation rate, but others such as lauroyl sarcosine, fatty alcohols and fatty acids tested did not show enhancing effect. In conclusion, the DGME-IPM or DGME-PGL cosolvent system proved to be a good vehicle to enhance the skin permeation of LP.

• 대한약학회:학술대회논문집
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• 대한약학회 2000년도 춘계총회 및 학술대회
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• pp.218.1-218.1
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• 2000

• Korean Chemical Engineering Research
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• 제55권5호
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• pp.600-608
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• 2017

산업현장에서 취급되거나 가공되는 원료의약품 분진의 폭발 위험성은 항상 존재하며, 이로 인한 폭발사고가 자주 발생되고 있다. 본 연구에서는 원료의약품 시료 3종의 분진폭발특성을 측정하였다. 주요 폭발특성 측정값은 록소프로펜산은 평균 입경이 $5.31{\mu}m$이며, $P_{max}$는 8.4 bar, 최소점화에너지는 1 mJ < MIE < 3 mJ이며 최소점화온도는 $550^{\circ}C$이다. 클로피도그렐 캄포르술폰산염은 평균 입경이 $95.63{\mu}m$이며, $P_{max}$는 7.9 bar, 최소점화에너지는 30 mJ < MIE < 100 mJ이며 최소점화온도는 $510^{\circ}C$이었다. 리팜피신은 평균 입경이 $26.48{\mu}m$이며 $P_{max}$는 7.9 bar, 최소점화에너지는 1 mJ < MIE < 3 mJ이며 최소점화온도는 $470^{\circ}C$로 나타났다. 이들 값을 적용하여 폭연지수($K_{st}$)와 폭발지수(EI)의 폭발위험등급을 구하고, 원료의약품 분진의 폭발 위험성을 비교 검토하였다. 그 결과 폭발 위험성은 록소프로펜산과 리팜피신의 폭발등급은 St 2이고 폭발위험등급은 severe이며, 클로피도그렐 캄포르술폰산염의 폭발등급은 St 1이고 폭발위험등급은 strong으로 나타났다.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2003년도 생물공학의 동향(XIII)
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• pp.549-553
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• 2003

TMB 크로마토그래피의 물질수지식으로부터 SMB 크로마토그래피의 디자인 파라미터들을 계산할 수 있으며, 이를 이용하여 6 칼럼 SMB 크로마토그래피 장치를 디자인하였다. SMB 크로마토그래피 장치는 4개의 multi position rotary valve를 사용하여 연속적으로 각 칼럼으로의 유로를 제어할 수 있으며, 효율적인 SMB 크로마토그래피 장치를 구현할 수 있다. 또한 회분식 실험으로부터 얻어진 $m_2,$ $m_3$ diagram으로부터 SMB 크로마토그래피의 조작에 필요한 파라미터들을 계산할 수 있었다.

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of the Pharmaceutical Society of Korea
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• pp.109.2-110
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• 2001

• 한국임상약학회지
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• 제27권3호
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• pp.195-197
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• 2017

A 74-year-old man suffering from cryptogenic organizing pneumonia (OP) visited our department with arthralgia accompanied with partial swellings of proximal interphalangeal and metacarpophalangeal joints with morning stiffness. A diagnose of rheumatoid arthritis (RA) was made. It was thought that OP was associated with RA. We initiated a treatment with salazosulfapyridine and loxoprofen for RA. Although this treatment was effective, it was discontinued due to the development of drug eruption. As an alternative, the patient was treated with prednisolone (PSL) and clarithromycin (CAM). This treatment demonstrated being effective for OP and RA, to a certain extent; however, the RA activity was not completely suppressed. In order to suppress the RA activity further, tacrolimus (TAC) was successfully added with increasing the dosage of CAM that is assumed to raise blood TAC concentrations. The present case shows that treatment with PSL, CAM and TAC may be effective in some cases of RA.

• Journal of Pharmaceutical Investigation
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• 제35권2호
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• pp.111-116
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• 2005

The unstirred water layer (UWL), which has been known to exist in the boundary of the intestinal lumen and intestinal wall, often behaves as an absorption barrier especially for lipophilic drugs. The intestinal absorption of drugs is often characterized using Caco-2 cell monolayers grown on Transwell polycarbonate membranes. The permeability $(P_{app})$ of drugs across the cell monolayer might be influenced by the agitation of the donor compartment, since the width of UWL on the surface of the cell monolayer would be reduced by the agitation. In this study, the effect of agitation of the donor compartment with 60 rpm on the permeability was measured for 12 drugs with a wide range of lipophilicity and permeability. The $P_{app}$ of mannitol, tributylmethyl ammonium, cimetidine, ranitidine, hydrocortisone, benzylpenicillin and loxoprofen was not influenced by the agitation, while the $P_{app}$ of theophylline, propranolol, YH439, phenylpropanolamine and testosterone was increased by the agitation. There was a significant correlation between the increase of $P_{app}$ by agitation and the lipophilicity for the compounds having $P_{app}>2{\times}10^{-5}$ cm/sec. No correlation was observed for the difference in $P_{app}$ by agitation and the molecular weight, or lipophilicity of the drugs. Therefore, the agitation rate of the donor compartment in the Caco-2 cell monolayer study should be carefully controlled in order to estimate $P_{app}$ reproducibly especially for lipophilic drugs.