• Journal of Pharmaceutical Investigation
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• v.40 no.6
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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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• v.29 no.1
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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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• v.39 no.2
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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.

• Journal of Pharmaceutical Investigation
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• v.37 no.5
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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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• v.32 no.4
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• pp.267-275
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• 2002

A self-microemulsifying drug delivery system (SMEDDS) was developed to increase the dissolution rate, solubility, and ultimately bioavailability of a poorly water soluble drug, lovastatin. SMEDDS was thε mixtures of oils, surfactants, and cosurfactants, which emulsify under conditions of gentle agitation, similar to those which would be encountered in the gastro-intestinal (GI) tract. Various types of self-emulsifying formulations were prepared using four types of oil (Capryol 90, Lauroglycol 90, Labrafil M 1944 CS and Labrafil M 2125), two surfactants (Cremophor EL and Tween 80), and three cosurfactants (Carbitol, PEG 400 and propylene glycol). Thε efficiency of emulsification was studied using a laser diffraction size analyzer to determine particle size distributions of the resultant emulsions. Optimized formulations selected for bioavailability assessment were Carpryol 90 (40%), Cremophor EL (30%) and Carbitol (30%). SMEDDS containing lovastatin (20 mg and 5 mg) were compared to a conventional lovastatin tablet $(Mevacor^{\circledR},\;20\;mg/tab)$ by the oral administration as prefilled hard gelatin capsules to fasted beagle dogs for in vivo study. The arεa under the serum concentration-time curve from time zero to the last measured time in serum, $AUC_{0{\rightarrow}24h}$, was significantly greater in SMEDDS, suggesting that bioavailability increase 130% and 192% by the SMEDDS, respectively. The self-emulsifying formulations of lovastatin afforded the improvement in absolute oral bioavailability relative to previous data of lovastatin tablet formulation. These data indicate the utility of dispersed self-emulsifying formulations for the oral delivery of lovastatin and potentially other poorly absorbed drugs.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.20 no.12
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• pp.555-562
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• 2019

This study was undertaken to develop a stable self-microemulsifying drug delivery system (SMEDDS) for trans-cinnamaldehyde, a known antibacterial and antifungal agent. A simultaneous analytical method was established for quantification of trans-cinnamaldehyde and its degradant, cinnamic acid. Various surfactants were applied to assess their effect on the aqueous solubility of trans-cinnamaldehyde, and pseudo-ternary phase diagrams were plotted. Of the various formulations tested, the liquid SMEDDS composed of trans-cinnamaldehyde (oil), Cremophor EL (surfactant) and Transcutol P (cosurfactant) at a volume ratio of 10/70/20, produced the smallest emulsion droplet size (around 23 nm). The stability test determined the superior stability of the trans-cinnamaldehyde SMEDDS with constant trans-cinnamaldehyde content and z-average diameter of emulsion, under accelerated and heat stressed condition. Thus, we believe that this novel trans-cinnamaldehyde SMEDDS formulation has the potential to be applied for the development of trans-cinnamaldehyde medicines in the pharmaceutical industry.

• Journal of Pharmaceutical Investigation
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• v.32 no.1
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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.

• Biomolecules & Therapeutics
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• v.8 no.3
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• pp.269-275
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• 2000

Silibinin(silybin) is the active component of silymarin from Silybum marianum and has hepato-protective effect. It is water-insoluble and has low bioavailability. To improve its bioavailability, self-micro-emulsifying drug delivery system (SMEDDS) has been developed by Hanmi Pharmaceutical Company (Silyma $n^{R}$ 140 soft capsule). In this study, the pharmacokinetic profiles of Silyma $n^{R}$ were examined and compared it with a reference preparation, L Caps140 of B Pharmaceutical Company. This study was approved by Yonsei University Severance Hospital IRB(approval No. CR0004) and followed the bioequivalence test guideline of Korean FDA. Eighteen healthy adult volunteers were allocated based on 2$\times$2 Latin square cross-over design. They were given 2 capsules (each contains silymarin 140 mg (60 mg as silibinin)) of either drug at each period and crossed over after a week of drug-free washout period. Blood concentration of silibinin was measured by HPLC. The $C_{max}$ and AUC of the Silyma $n^{R}$ were 1542.0 $\pm$ 402.7 ng/ml and 3323.3 $\pm$ 824.7 ng.h/ml, respectively, and were significantly higher than those of reference preparation. The Tmax was 0.8 $\pm$ 0.3 h and significantly shorter than reference preparation. The $K_{e}$ and $T_{1}$2/ of both drugs were comparable. Percent differences in means against reference preparation were +88.3% for AUC, +222.6% for $C_{max}$, and -61.1% for $T_{max}$./.>././.>./.

• Journal of Pharmaceutical Investigation
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• v.37 no.6
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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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• v.41 no.2
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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.