• Journal of Pharmaceutical Investigation
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• 제33권3호
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• pp.201-208
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• 2003

Pharmacokinetics and oral bioavailability of levosulpiride was determined in Korean healthy male volunteers. Thirty subjects received a single oral dose (25 mg) of a tablet in a randomized $2{\times}2$ cross-over design. The plasma concentrations of levosulpiride were measured by HPLC and compared with those reported in the literature. Pharmacokinetic parameters for $Isomeric^{\circledR}$ tablet (levosulpiride 25 mg) were revealed as follows: $AUC_{inf}\;737.1{\pm}176.9\;ng{\cdot}hr/ml,\;C_{max}\;56.4{\pm}20.1\;ng/ml,\;T_{max}\;4.2{\pm}1.6\;hr,\;K_a\;1.00{\pm}1.09\;hr^{-1},\;K_{el}\;0.08{\pm}0.02\;hr^{-1},\;and\;t_{1/2}\;8.8{\pm}1.9\;hr$. The rate constant of the absorption phase was obtained based on the first-order kinetics. In the aspect of bioavailability, $Isomeric^{\circledR}$ tablet was bioequivalent to the other product $(Levopride^{\circledR}\;tablet)$ available in the Korea market. Intersubject variations and race differences were show in comparison with the published data in the literature, even though there was a linear relationship between dose ad extent of bioavailability.

• Journal of Pharmaceutical Investigation
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• 제27권4호
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• pp.323-329
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• 1997

Ipriflavone is non-hormonal antiosteoporotic drug which inhibits bone resorption by reducing recruitment and/or differentiation of osteoclasts, and stimulates proliferation and differentiation of osteoblast, and also enhances calcitonin secretion in the presence of estrogen. Although some kinds of immediately-released preparation of ipriflavone are available in commercial market, in present study, we tried to formulate sustained-release tablet using coating method with hydrophobic and hydrophilic coating materials. In vitro dissolution test was applied to evaluate sustained-release patterns of several test preparations (Test tablet A, B and C) designed using different preparation method or different compositions. From the results of dissolution test, test tablet A which showed suitable dissolution profile was selected as the candidate of new product. Pharmacokinetic evaluation of test drug, ipriflavone sustained-release tablets, was conducted in 6 beagle dogs weighing $11.5{\pm}0.5\;Kg$ compared with $Theobon^{\circledR}$ tablet, immediately-released tablet (Kukjae Pharm. Co.) as reference drug. Two products were randomly administered to 6 beagle dogs, and after 1 week, cross-over study was conducted. From the present study, AUC and $T_{max}$ of test product were significantly different from those of reference product (p<0.05), respectively$(AUC\;:\;3646.28{\pm}472.56\;vs\;3646.28{\pm}472.56\;ng{\cdot}hr/ml,\;T_{max}\;:\;4.33{\pm}1.03\;vs\;1.42{\pm}0.38\;hr)$. But $C_{max}$ was not significantly different between two products (p>0.05) $(\;512.52{\pm}48.18\;vs\;443.97{\pm}140.53\;ng/ml)$. From the results of pharmacokinetic evaluations, it was noted that absorption amount of test product was increased, but absorption rate was delayed and $C_{max}$ of two products were not changed. And it was concluded that redesign of the sustained-release preparation which has a lower content of iprifavone rather than test tablet A must be considered.

• Journal of Pharmaceutical Investigation
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• 제37권3호
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• pp.167-171
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• 2007

Itraconazole is one of the most potent antifungal agents available in the market today. However, the low bioavailability due to its poor-water solubility calls for an alternative formulation to the current oral type. A topical itra-conazole-containing formulation may be of use for several reasons including the opportunity to reduce adverse events and generate high local tissue levels, more rapid drug delivery, and lower systemic exposure. The purpose of the present study was to investigate the vehicles for topical skin delivery of itraconazole. The effect of formulations on the hairless mouse skin permeation and deposition of itraconazole was determined using Franz diffusion cells at $37^{\circ}C$. Benzyl alcohol in micro-emulsion significantly increased the solubility of itraconazole, thereby increasing the skin permeation rate. However, lipo-some formulation showed the lowest solubility and permeation rate of itraconazole. Although the solubility of itraconazole in hydrogel formulation was lower than that in microemulsion, skin permeation rate was significantly higher probably due to its adhesive property. Therefore, microemulsion-based hydrogel formulation is expected to synergistically increase the skin permeation rate and skin deposition of itraconazole.

• 한국산학기술학회논문지
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• 제18권12호
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• pp.329-334
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• 2017

본 논문은 새로운 과립형태의 구강청결제 개발에 있어 동등한 항균력을 가지면서 고형상에서 주성분간의 공융혼합물 생성에 따른 과립의 흐름성 부족을 개선하기 위해 과립의 표면을 흡착시키는 Magnesium aluminometasilicate (Neusilin)이라는 물질을 활용하여 흐름성을 개선하고 부가적으로 구강에서의 붕해시간 및 잔물감이 적은 특성을 가지는 새로운 과립형태의 구강청결제를 제조하였다. 제조된 과립의 흐름성, 밀도, 건조감량 등의 과립특성에 대한 확인을 통해 Neusilin의 양이 전체 과립양 대비 10%이상이 투입되었을 경우 과립의 특성이 개선되는 결과를 확인하였다. 또한 인공타액에서의 붕해시험 및 사람의 구강에서 붕해시간과 잔여물시험 등의 관능시험을 진행하여 보다 개선된 붕해특성 및 관능시험 결과를 확인할 수 있었으며 항균시험을 통해서 이미 시장에서 판매중인 액제형 구강청결제와 동등한 항균력을 보여주는 것으로 확인하였다. 본 연구를 통해 제조된 과립형태의 구강청결제 조성물은 공융혼합물로서 유사한 특성을 가지는 서로 다른 약물을 동시에 함유하는 의약품의 개발에 활용될 수 있어 제약산업의 의약품 개발에서 유용할 것으로 사료된다.

• Journal of Pharmaceutical Investigation
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• 제24권2호
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• pp.57-65
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• 1994

To increase the dissolution rate of practically insoluble biphenyl dimethyl dicarboxylate (DDB), various solid dispersions were prepared with water soluble carriers, such as povidone (PVP K-30), poloxamer 407, sodium deoxycholate (SDC) and polyethylene glycol (PEG) 6000, at drug to carrier ratios of 1:3, 1:5 and 1:10 (w/w) by solvent or fusion method. Dissolution test was performed by the paddle method. The dissolution rate of DDB tablets (25 mg) on market was found to be very low (11.44, 9.02 and 6.42% at pH 1.2, 4.0 and 6.5 after 120 min, respectively). However, dissolution rates of DDB from various solid dispersions were very fast and reached supersaturation within 10 min. DDB-PEG 6000 solid dispersion appeared to be better in enhancing the in vitro dissolution rate than others. Furthermore, the incorporation of DDB and phosphatidylcholine (PC) into ${\beta}-cyclodextrin$ at ratios of 1:2:20, 1:5:20 and 1:10:20 resulted in a 4.9-, 11.2- and 19.6-fold increase in DDB dissolution after 120 min as compared with the pure drug, respectively. This might be attributed to the formation of lipid vesicles which entrapped a certain concentration of DDB during dissolution. On the other hand, the permeation of DDB through rabbit duodenal mucosa was examined using some enhancers such as SDC, sod. glycocholate (SGC) and glycyrrhizic acid ammonium salt (GAA). Only trace amounts of DDB were found to permeate through deuodenal mucosa in the absence of enhancer. SDC was found to markedly decrease the permeation flux of DDB, however, SGC and GAA (5 mM) enhanced the flux of DDB 1.6 and 2.4 times higher as compared with no additive, respectively.

• 한국한의학연구원논문집
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• 제7권1호
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• pp.77-84
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• 2001

A survey was conducted to investigate the attitudes of pharmaceutical companies toward the status and permission of R & D of herbal products. The survey's results showed that some of them(42.9%) was conducting the R&D, and others(57.1%) were not conducting. As the results of analysis on the reason of R&D conducting, some of them(42.3%) answered that R&D of herbal products is more effective and powerful than these of synthetic products. And 23.1% answered that the cost of R&D is low and the time required is short. And another 23.1% answered that it has marketability and competitive power. As the results of analysis on the marketability of herbal products in Pharmaceutical Market, most of them(78.6%) answered that it seems enough. As the result of the comparison of synthetic drug and herbal products, the proportion of R&D investment on herbal products was lower than synthetic products in the preclinical study, the first clinical study and the second clinical study, and higher than in the third clinical study and the NDA. And the periods of R&D was long in most procedure except synthesis of new materials. As the results of analysis on the recognition of related regulation, most of them(73%) was yes. And 35.2% of the subjects thinks it enough.

• Journal of Pharmaceutical Investigation
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• 제32권1호
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• pp.27-33
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• 2002

A self-microemulsifying drug delivery system(SMEDDS) composed of Cremophor $EL^{\circledR},\;Labrasol^{circledR}$, and Lauroglycol $FCC^{circledR}$ was prepared for the enhancement of solubility, dissolution rate and bioavailability of ibuprofen(IBP), which is water-insoluble but soluble in oils and surfactants. Phase diagram with various regions including microemulsion area was depicted. The SMEDDS was encapsulated in soft gelatin capsules and their dissolution characteristics in various media were observed in comparison to the generic products commercially available in the market. Soft capsules of SMEDDS formulation showed better dissolution profiles, especially in acidic condition, than the others. For the period of 1 hr dissolution in pH 1.2 medium, it reached over 70% dissolution from soft capsules, compared to less than 40% dissolution from commercial reference tablets. On the other hand, in vivo pharmacokinetic parameters were obtained after oral administrations of different IBP preparations to Sprague Dawley rats. SMEDDS formulation showed higher $C_{max}$ and greater $AUC_{0-5hr}$ than the suspension of reference tablet or IBP powder. Therefore, it is possible to conclude that a newly developed soft capsules employing SMEDDS provides an alternative preparation to improve oral bioavailability of IBP.

• Journal of Pharmaceutical Investigation
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• 제37권6호
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• pp.359-364
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• 2007

Pine bark extract is well-known as a very powerful antioxidant, anti-inflammatory, and antibiotic material. French maritime pine bark extract ($Pycnogenol^{(R)}$) of Horphag Research has monopolized the world market over 30 years. Korean red pine bark extract ($Pinexol^{(R)}$) was first manufactured by the patent technology of NutraPharm in Korea in 2006. Feasibility of topical gel and patch formulations of Pinexol was systematically investigated by evaluating the skin absorption of catechin as a reference compound. In vitro hairless mouse skin absorption of catechin from gel formulation was higher than that from patches. However, significant amount of catechin was also deposited inside the skin from patch formulations, which were dependent on the types of pressure sensitive adhesives. Thus, it seems to be feasible to control the topical delivery of Pinexol by using both gel and patch formulations, and be necessary to conduct further systematic investigation.

• Mass Spectrometry Letters
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• 제10권2호
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• pp.66-70
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• 2019

Rivaroxaban (RRN) is the first available active direct factor Xa inhibitor (anticoagulant) with oral administration. Due to its success in market, there have been efforts to develop various RRN formulations, and the development of good analytical methods for its in vivo evaluation is an essential prerequisite. Thus, here, a simple and efficient method to determine RRN in rat plasma using liquid-liquid extraction (LLE) and liquid chromatography and multiple reaction monitoring (LC-MRM) was presented. The use of ethyl acetate as the LLE solvent results appropriate extraction and purification of RRN and it also helps the significant reduction of rat plasma volume required for RRN quantitation. The developed method showed good analytical performance including specificity, linearity ($r^2{\geq}0.999$ within 0.5 - 500 ng/mL), sensitivity (the lower limit of quantitation at 0.5 ng/mL), accuracy (89.3 - 107.0%), precision (${\geq}12.7%$), and recovery (89.2 - 105.7%). Additionally, RRN in sample extracts showed good stability. Finally, the applicability of the validated method to the PK evaluation of RRN was confirmed after its oral administration to normal rats. The present method is the first analytical method employing LLE for the simple and efficient extraction and purification of RRN in rat plasma. Therefore, the present method can contribute to the development of new RRN formulations as well as to the monitoring of RRN in special clinical situations through its efficient determination in various samples with or without minor modification.

• 한국식품저장유통학회지
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• 제24권8호
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• pp.1094-1102
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• 2017

대구시내 대형마트에서 유통되고 있는 스테인레스, 경질알루미늄, 연질알루미늄 재질 코펠 및 불소수지 코팅 불판에 대해 0.5% citric acid 용액에서 용출되는 유해 금속을 유도결합플라즈마 발광광도측정기(ICP-OES)로 측정한 결과, 식품용 기구 및 용기 포장 공전에 기준이 설정된 납, 카드뮴, 비소, 니켈의 경우는 모두 적합한 것으로 나타났다. 그러나 용출 용액과 사용 환경에 따라 그 용출 정도에 차이가 있는 것으로 나타났다. 증류수, 0.5% citric acid 용액, 1% NaCl 용액 등 용출 용액을 달리하여 30분간 가열한 뒤 평균 용출량을 비교한 결과, 증류수에서 경질알루미늄 재질 코펠의 알루미늄 용출량이 0.007 mg/L 수준이었으나, 0.5% citric acid 용액에서는 스테인레스 재질 코펠은 0.021 mg/L, 경질알루미늄 재질 코펠은 51.97 mg/L, 연질알루미늄 재질 코펠은 24.89 mg/L, 불소수지 코팅 불판은 0.040 mg/L로 증류수와 1% NaCl 용액에서의 용출량보다 높았다. 1% NaCl 용액에서 비소는 스테인레스와 연질알루미늄 재질 코펠 0.006 mg/L, 경질알루미늄 재질 코펠 0.008 mg/L로 증류수와 0.5% citric acid 용액에서의 용출량보다 다소 높게 용출되었다. 0.5% citric acid 용액에서 니켈이 스테인레스 재질 코펠이 0.007 mg/L로 증류수와 1% NaCl 용액에서의 용출량보다 다소 높게 용출되었는데, 이는 스테인레스 코펠의 니켈 조성 특성 때문으로 사료된다. 카드뮴은 모든 용액에서 검출되지 않았다. 물리적 스크래치를 가한 후의 용출 용액에 따른 유해 금속 용출량은 스크래치를 가하기 전보다 모든 용액에서 전반적으로 증가하는 것으로 조사되었다. 특히, 0.5% citric acid 용액에서는 스테인레스와 경질알루미늄 재질 코펠에서 카드뮴이 용출되는 것으로 나타났다. 용출 시간에 따른 유해 금속 용출량 변화를 살펴보면, 증류수에서는 경질알루미늄, 연질알루미늄 재질 코펠과 불소수지 코팅 불판의 알루미늄 용출량이 증가하였다. 0.5% citric acid 용액에서는 스테인레스, 경질알루미늄, 연질알루미늄 재질 코펠의 니켈과 알루미늄 용출량이 증가하였고, 불소수지 코팅 불판은 납, 비소, 알루미늄 용출량이 증가하였다. 1% NaCl 용액에서는 스테인레스, 경질알루미늄 재질 코펠과 불소수지 코팅 불판의 비소 용출량이 증가하였고, 연질알루미늄 재질 코펠의 비소와 알루미늄 용출량이 증가하였다.