• Journal of Pharmaceutical Investigation
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• 제40권6호
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• pp.339-345
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• 2010

Fenofibrate has been used for many years to lower cholesterol levels and its pharmacokinetic profile is well understood. However, due to its low solubility in water, it has low bioavailability after oral administration. In order to improve the dissolution rate, fenofibrate was formulated into a self-microemulsifying drug delivery systems (SMEDDS). We used pseudo-ternary phase diagrams to evaluate the area of microemulsification, and an in vitro dissolution test was used to investigate the dissolution rate of fenofibrate. The optimized formulation for in vitro dissolution assessment consisted of Lauroglycol FCC (60%), Solutol HS 15 (27%), and Transcutol-P (13%). The mean droplet size of the oil phase in the microemulsion formed from the SMEDDS was about 130 nm. The dissolution rate of fenofibrate from SMEDDS was significantly higher than that of the reference tablet. Our studies suggested that the fenofibrate containing SMEDDS composition can effectively increase the solubility and oral bioavailability of poorly water-soluble drugs.

• Journal of Pharmaceutical Investigation
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• 제34권1호
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• pp.35-42
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• 2004

Ibuprofen (IBU), is a non-steroidal anti-inflammatory drug, used to treat rheumatoid arthritis, removal of fever and mild to moderate pain. Because of small dosage and very low accumulation in the body, IBU has been used to heal children's fever. However, IBU was very low solubility in a low pH and water (in water $0.03{\sim}2.5$ mg/ml). A nanoemulsion containing IBU by means of self-microemulsion drug delver system (SMEDDS) was prepared in order to enhance the solubility of IBU. The SMEDDS was composed of cosurfactant, oil and surfactant The solubility of IBU in various components such as cosurfactant, oil and surfactant was examined. $Carbitol^{\circledR}\;(386.99{\pm}20.5\;mg/ml)$ as a cosurfactant, $Labrafil^{\circledR}$　 M1944CS $(90.16{\pm}1.60mg/ml)$ as an oil and $Cremopher^{\circledR}$　 RH-40 $(239.01{\pm}2.8\;mg/ml)$ as a surfactant were used in this study for preparing SMEDDS. Optimized formulation of SMEDDS was obtained by phase diagram which express the section of nanoemulsion formation. The SMEDDS containing IBU had higher dissolution rate than conventional IBU sirups. Thus the SMEDDS was a potential candidate of stable conventional and effective oral dosage form for IBU.

• Journal of Pharmaceutical Investigation
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• 제39권2호
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• pp.111-115
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• 2009

The pharmacokinetics of cyclosporin A (CsA) after single and multiple oral dosing of new CsA self-micro-emulsifying drug delivery system (SMEDDS) in dogs were estimated. A single dose study was performed following a two-way crossover design against six dogs with reference SMEDDS. For a multiple dose study, three dogs were allocated for each drug, and 100 mg of drug was administered daily for 6 days. Whole blood concentration of CsA was analyzed by radio-immunoassay. Both drug showed identical blood concentration profiles in both studies, and no statistical difference was detected in pharmacokinetic parameters. The relative bioavailabilities of test SMEDDS were 91.4% and 89.1%, respectively, in the single dose study and the last day of multiple dose study. Especially, multiple dose study proved the good relationship between C-0/C-2 and AUC for reference SMEDDS, which is an indispensable part of therapeutic drug monitoring. These results suggest newly formulated CsA SMEDDS possibly shows identical pharmacokinetics and pharmacodynamic behaviors in clinical trials.

• 한국산학기술학회논문지
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• 제20권12호
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• pp.555-562
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• 2019

본 연구의 목적은 다양한 항균활성을 지닌 천연물 유래 물질 신남알데히드를 이용한 안정한 자가미세유화 약물전달시스템을 개발하는 것이다. 이러한 목표를 달성하기 위하여 신남알데히드의 주 분해산물인 신남산과 신남알데히드의 동시 정량법을 확립하였으며, 설정된 분석법을 이용한 용해도 시험으로 신남알데히드에 대한 용해도 개선효과가 우수한 계면활성제를 선별하였다. 계면활성제로 Cremophor EL, 공계면활성제로 Transcutol P를 이용한 신남알데히드의 pseudo-ternary phase diagram을 작성하여 에멀전의 입자크기를 최소화시킬 수 있는 조성비로 신남알데히드 : Cremophor EL : Trasncutol P = 10 : 70 : 20%(v/v/v)인 SMEDDS 조성물을 제조한 후 안정성 시험을 통해 신남알데히드의 함량변화 및 에멀전의 입자크기 변화에 대해 확인하였다. 본 연구를 통해 제조된 신남알데히드의 자가유화 나노에멀전은 신남산의 생성량이 적고 신남알데히드의 함량 저하 속도가 느려 안정성이 우수하였으며, 안정성 기간 중에 최초의 입자크기를 잘 유지하는 특성이 확인되었다. 따라서 이 조성물은 신남알데히드를 위한 의약품 제형으로의 활용 가능성이 높을 것으로 사료된다.

• 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.339-347
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• 2007

SMEDDS is mixture of oils, surfactants, and cosurfactants, which are emulsified in aqueous media under conditions of gentle agitation and digestive motility that would be encountered in the gastro-intestinal(GI) tract. The main purpose of this work is to prepare self-microemulsifying drug delivery system(SMEDDS) for oral bioavailability enhancement of a poorly water soluble drug, atorvastatin calcium. Solubility of atorvastatin calcium was determined in various vehicles. Pseudo-ternary phase diagrams were constructed to identity the efficient self-emulsification region and particle size distributions of the resultant micro emulsions were determined using a laser diffraction sizer. Optimized formulations for in vitro dissolution and bioavailability assessment were $Capryol^{(R)}$ 90(50%), Tetraglycol(16%), and $Cremophor^{(R)}$ EL(32%). The release rate of atorvastatin from SMEDDS was significantly higher than the conventional tablet ($Lipitor^{(R)}$), 2-fold. Our studies illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as atorvastatin calcium by the oral route.

• Journal of Pharmaceutical Investigation
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• 제29권1호
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• pp.37-45
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• 1999

ABSTRACT-A self-microemulsifying drug delivery system (SMEDDS) was developed to enhance the solubility and dissolution rate of poorly water soluble drug, biphenyl dimethyl dicarboxylate, DDB. The system was optimized by evaluating the solubility of DDB and the microemulsion existence range after the preparation of microemulsions with varying compositions of triacetin and surfactant-cosurfactant mixtures (Labrasol as surfactant (S) and the combination of Transcutol, Cremophor RH 40 and Plurol oleique as cosurfactant (CoS)). SMEDDS in this study markedly improved the solubility of DDB in water up to 10 mg/ml and the size of the o/w microemulsion droplets measured by dynamic light scattering showed a narrow monodisperse size distribution with an average diameter less than 50 nm. The microemulsion existing range is increased proportional to the ratio of S/CoS, however, it decreased remarkably as the oil content was more than 20%. In vitro dissolution study of SMEDDS showed a significantly increased dissolution rate of DDB in water (> 12 fold over DDB powder), and SMEDDS also had significantly greater permeability of DDB in Caco-2 cell compared to powders.

• Journal of Pharmaceutical Investigation
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• 제37권5호
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• pp.291-295
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• 2007

Prostaglandin $E_1\;(PGE_1)$ was formulated as two self-microemulsifying drug delivery systems (SMEDDS) composed of Cremophor $EL^{(R)}$ or Cremophor $ELP^{(R)}$ as a surfactant, ethanol as a cosurfactant and Labrafac $CC^{(R)}$ as an oil to develop liquid preparation for the treatment of erectile dysfunction. In pseudo-ternary phase diagram, viscous gel area and microemulsion area were defined. In the measurement of viscosity, the viscosity of two formulations increased gradually upon the addition of water and it decreased from the water contents over 40%. With excessive water, the present systems formed a microemulsion spontaneously. From these results, rte could expect that the present liquid $PGE_1$ SMEDDS formulations might stay within the urethra in the viscous state when contacting the moisture of the urethra and can be easily eliminated by urination. In long-term stability study, we could select one formulation more stable at the shelf storage condition of $4^{\circ}C$.

• Journal of Pharmaceutical Investigation
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• 제33권2호
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• pp.121-127
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• 2003

The objective of this study was to solidify the simvastatin self-microemulsifying drug delivery system (SMEDDS) and to improve the encapsulation efficiency of solidified alginate beads using sodium alginate. Typical simvastatin SMEDDS was composed of various oils, surfactants and cosurfactants. Also solidified-alginate beads was prepared by crosslinking liquid emulsion mixtures containing sodium alginate and other excipients (cetylpyridinum chloride (CP-Cl), hydroxypropyl methylcellulose, starch and so on). in $CaCl_2$ solution, it has been investigated that the drug release pattern and encapsulation efficiency were varied with the ratio of cationic lipid (CP-Cl). Solidified sodium alginate beads containing simvastatin SMEDDS were redispersed into media without re-aggregation. Oil droplet size of redispersed solidified-beads in media produced smaller than the initial size. The density of beads and drug loading amount were increased with increasing cationic lipid content. These systems have advantages of storage stability and predictability of drug release rate.

• Journal of Pharmaceutical Investigation
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• 제41권2호
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• pp.103-109
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• 2011

The objective of the study was to prepare self-microeulsifying drug delivery system (SMEDDS) incorporating atorvastatin calcium and evaluate its properties and oral bioavailability. Solubility of atorvastatin in various vehicles was determined. Pseudo-ternary phase diagrams were constructed to identify the good self-emulsification region. The droplet size distributions of the resultant emulsions were determined by dynamic light scattering measurement. The mean droplet size of chosen formulation (20% ethyl oleate, 40% tween-80, 40% Carbitol$^{(R)}$) was $23.4{\pm}1.3$ nm. The SMEDDS incorporating atorvastatin calcium appeared to be associated with better performance in dissolution and pharmacokinetic studies, compared with raw atorvastatin calcium. In dissolution test, the release percentage of atorvastatin from SMEDDS mixture could rapidly reach more than 95% within 3 min. Oral $AUC_{0{\rightarrow}8hr}$ values in SD rats was $1994{\pm}335\;ng{\cdot}hr/mL$, which significantly increased (P<0.05) compared with raw atorvastatin calcium. The SMEDDS formulation was relatively stable when stored at $4^{\circ}C$ during 3 months. Our studies illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as atorvastatin, by the oral route.