• The Korean Journal of Physiology and Pharmacology
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• 제17권1호
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• pp.9-13
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• 2013

The aim of the present study was to examine the effect of micellar systems on the absorption of beta-lapachone (b-lap) through different intestinal segments using a single-pass rat intestinal perfusion technique. B-lap was solubilized in mixed micelles composed of phosphatidylcholine and sodium deoxycholate, and in sodium lauryl sulfate (SLS)-based conventional micelles. Both mixed micelles and SLS micelles improved the in situ permeability of b-lap in all intestinal segments tested although the mixed micellar formulation was more effective in increasing the intestinal absorption of b-lap. The permeability of b-lap was greatest in the large intestinal segments. Compared with SLS micelles, the effective permeability coefficient values measured with mixed micelles were 5- to 23-fold higher depending on the intestinal segment. Our data suggest that b-lap should be delivered to the large intestine using a mixed micellar system for improved absorption.

• Journal of Pharmaceutical Investigation
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• 제23권2호
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• pp.71-80
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• 1993

The purpose of this study was to compare the intrinsic absorptivity of piperacillin in the jejunum and the nasal cavity, to investigate the effect of bile salts, fatty acids and their mixed micelles on the intestinal and nasal absorption of piperacilIin, to examine the reversibiIity of bile salt-fatty acid mixed micelles absorption promoting action and to design an effective intranasal drug delivery system for antibiotics. And absorption promoters used were bile salts [sodium cholate (NaC), sodium glycocholate (NaGC)], unsaturated fatty acids [oleic acid (OA), linoleic acid (LA)] and their mixed micelles (NaC-LA). The present study employed the in situ nasal and intestinal perfusion technique in rats. The apparent permeabilities $(P_{app})$ of piperacillin were $0.40{\pm}0.04{\times}10^{-5}cm/sec(mean{\pm}S.E)$ in the jejunum and $1.32{\pm}0.08{\times}10^{-5}\;cm/sec$ in the nasal cavity, which indicated that intrinsic absorptivity of piperacillin was greater in the nasal cavity than in the jejunum. When absorption promoters were used in the rat nasal cavity, the decreasing order of apparent piperacillin permeability $(P_{app},\;10^{-5}\;cm/sec)$, corrected for surface area of absorption, was NaC-LA $(4.62{\pm}0.16)$> NaC $(4.36{\pm}0.32)$>LA$(2.24{\pm}0.26)$ NaGC $(2.17{\pm}0.21)$>OA $(1.53{\pm}0.16)$. The increase in permeability of piperacillin was 3.5-fold in the rat nasal cavity and 1.5-fold in the rat jejunum for formulations containing NaC-LA mixed micelles as compared to those without absorption enhancer. The effect of NaC-LA mixed micellar solutions was synergistic and was greater than that with single adjuvant. The reversibility of nasal mucosal permeability was observed within approximately 2 hr after removal of NaCLA mixed micelles from the nasal cavity. These results suggest that NaC-LA mixed micelles can be used as nasal mucosal absorption promoters of poorly absorbed drugs.

• Bulletin of the Korean Chemical Society
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• 제7권2호
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• pp.113-116
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• 1986

Spectral behaviors of cationic dyes, methylene blue(MB) and acridine orange(AO), with varying concentrations of sodium dodecylsulfate(SDS) were studied. At low concentration of SDS(<1mM), these dyes formed insoluble dye-surfactant aggregates. When [SDS] is 4-5 mM, the aggregates were dissolved into mixed micelles of constant composition. At higher concentration of [SDS], the composition of mixed micelles were changed with [SDS], resulting only monomeric form of dyes in micelles. AO-SDS system showed greater aggregating and less dissolving properties, and weaker effect of salt than MB-SDS system did. These were attributed to the greater hydrophobic nature of the former dye. The monomer/dimer ratios of dyes in mixed micelles at given [SDS] were greatest at $20^{\circ}C$, reflecting the dependency of CMC of the surfactant on temperature.

• 한국응용과학기술학회지
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• 제18권4호
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• pp.249-253
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• 2001

A proposed method of determining the composition of mixed micelles in equilibrium with monomer of known composition is described. The systems were sodium ${\alpha}-sulfonated$ dodecanoyl ethyl esther (${\alpha}-SR_{12}Et$) or sodium dodecyl sulfate(SDS)-polyoxyethylene 23 lauryl ether (Brij 35) un water and in 0.1M sodium chloride solution at $25^{\circ}C$. This technique applies the Gibbs-Duhem equation to the mixed micelles, which is treated as a pseudophase. This proposed methodology, which needs only critical micelle concentration data as a function of monomer composition, is applied to an anionic/nonionic surfactant pair. The calculated monomer-micelle equilibrium is found to be very similar to the much-used regular solution for nonideal systems.

• Bulletin of the Korean Chemical Society
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• 제10권5호
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• pp.437-442
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• 1989

The cmc's of sodium dodecyl sulfate (SDS)/Triton X-100 surfactant mixtures were determined by surface tension measurement at various surfactant compositions. The cmc values were lower than those predicted from ideal mixture. The regular solution theory was applied to calculate the interaction parameter, micellar composition, and the activity coefficients of surfactants in the mixed micelle. The interaction parameter (${\beta}$) was - 2.1. The nonideality arised largely from decreased activity of SDS in the mixed micelle. The mean aggregation numbers (${\bar{n}}$) and micropolarity of hydrocarbon region of the mixed micelles were determined by luminescence probe techniques. The total aggregation number (${\bar{n}}_{SDS}+{\bar{n}}_{TX}$) in mixed micelles showed little dependency on the composition of the micelle. The apparent dielectric constant of the hydrocarbon region of the micelle vs micellar composition plot showed positive deviation from linearity. Emission and emission quenching of excited tris(2,2'-bipyridine)ruthenium(Ⅱ) cation, $(Ru(bpy)_3^{2+})$, by methylviologen ($MV^{2+}$) were also investigated in the mixed micellar solutions. The quenching rate was lowest when the mole fraction of SDS in the surfactant mixtures (${\alpha}_{SDS}$) is about 0.25 and highest at ${\alpha}_{SDS}$ = 0.85. This was explained in terms of combined effects of binding of the cations with the micelle and mobility of the bound cations on the surface of the micelles.

• Journal of Pharmaceutical Investigation
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• 제22권3호spc1호
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• pp.17-34
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• 1992

A novel drug delivery system, detergent-phospholipid mixed micelles as proliposomes, for water-insoluble compounds was developed by investigating (i) spontaneous formation of small unilamellar vesicles (SUV) from bile salt-egg phosphatidylcholine mixed micelles, (ii) the molecular mechanism of micelle-to-vesicle transition in aqueous mixtures of detergent-phospholipid, (iii) preparation and screening of a suitable liposomal formulation for a lipophilic drug: solubilization of the drug within the lipid bilayer, evaluation of the solubility limit, and characterization of the resulting product with respect to the physical properties and stability of the drug in the system, and (iv) testing antitumor activity in vitro. The results showed that the new carrier had a strong possibility to be a biocompatible universal formulation for water-insoluble drugs.

• 식품보건융합연구
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• 제5권4호
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• pp.13-17
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• 2019

Amiodarone hydrochloride is an antiarrhythmic agent which has low aqueous solubility and presents bioavailability problem. These properties are a challenge for the pharmaceutical industry. Inclusion of lipophilic compound in the hydrophobic core of micelles, i.e. self-assembled structures based on surfactants in aqueous solution, is one way of increasing the solubility. Intravenous formulation of amiodarone hydrochloride with polysorbate 80 as a detergent and benzyl alcohol as a co-solvent is used in medical practice. This paper aimed to study the effect of polysorbate 80 and benzyl alcohol on the water solubility of amiodarone hydrochloride. Formation of mixed micelles consisting of nonionic surfactant polysorbate 80 and cationic amiodarone with chloride counterion was investigated by fluorescence spectroscopy. Benzyl alcohol was found to decrease the stability of the mixed micelles and lead to crystallization of amiodarone hydrochloride. The greatest amounts of crystals formed at 4℃ for 30 days in the model drug solutions with polysorbate 80 concentrations of 100.1 mg/mL and 97.9 mg/mL. A change of the polysorbate 80 concentration and avoidance the use of benzyl alcohol are recommended to improve the stability of the parenteral dosage form. These results can open new perspectives in the optimization of amiodarone intravenous formulations.

• Journal of Pharmaceutical Investigation
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• 제35권5호
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• pp.333-336
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• 2005

The objective of this study was to investigate the stability of tetracycline HCl on encapsulation into and inside reverse micelles. To do so, tetracycline HCl was first mixed with cetyltrimethylammonium bromide, water and ethyl formate to make reverse micelles. The degradation kinetics of tetracycline HCl inside the reverse micelles was then assessed by scrutinizing its stability data. Under our experimental conditions, the reverse micelles formed spontaneously in absence of any mixing devices. During the preparation of the reverse micelles, however, considerable portions of tetracycline HCl underwent a chemical reaction (e.g., epimerization). For instance, $51.4{\pm}0.6%$ of an initial concentration of tetracycline HCl was transformed into a degradation product. Once dissolved inside the reverse micelles, the degradation of tetracycline HCl followed an exponential decay pattern. The plot of log{the degradation rate of tetracycline HCl} versus log{tetracycline HCl concentration} made it possible to determine the order of degradation reaction and rate constant. It was proven that the degradation of tetracycline HCl inside the reverse micelles followed a first order kinetics with a rate constant of 0.0027 $hour^{-1}$. Meriting further investigation might be formulation studies to stabilize tetracycline HCl on encapsulation into and inside the reverse micelles.

• Bulletin of the Korean Chemical Society
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• 제22권9호
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• pp.1009-1014
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• 2001

In aqueous mixtures of cationic OTAC (octadecyl trimethyl ammonium chloride) and anionic ADS (ammonium dodecyl sulfate) surfactants, mixed micelles were formed at low (< 0.2 wt %) total surfactant concentrations. For these mixtures mixed micelliza tion and interaction of surfactant molecules were examined. Mixed critical micelle concentration (CMC), thermodynamic potentials of micellization, and minimum area per surfactant molecule at the interface were obtained from surface tensiometry and electrical conductometry. The mixed micellar compositions and the estimation of interacting forces were determined on the basis of a regular solution model. The CMCs were reduced, although not substantial, and synergistic behavior of the ADS and OTAC in the mixed micelles was observed. The CMC reductions in this anionic/cationic system were comparable to those in nonionic/anionic surfactant systems. The interaction parameter $\beta$ of the regular solution model was estimated to be -5 and this negative value of $\beta$ indicated an overall attractive force in the mixed state.

• Bulletin of the Korean Chemical Society
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• 제23권1호
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• pp.93-97
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• 2002

Poly(ethylene glycol)-phosphatidylethanolamine conjugate (PEG-PE) has been used in preparing longcirculating liposomes. As a substitute for PEG-PE which can also be used in the long-circulating liposome formualtions, but can be prepared more readily with a lower cost, PEG-Phe-Chol was synthesized from PEG, phenylalanine, and cholesterol. The addition of the PEG derivative to distearoylphosphatidylcholine (DSPC) led to the formation of mixed micelles as well as liposomes when the derivative content was 10 mol% or greater. On the other hand, the addition of just 5 mol% PEG-Phe-Chol to dioleoylphosphatidylethanolamine (DOPE) generated mixed micelles as well as liposomes, but the formation of mixed micelles was completely inhibited by the addition of cholesterol. The leakage of entrapped calcein out of DOPE/cholesterol (7/3) liposomes containing 5 mol% PEG-Phe-Chol was about 45% during the incubation time for 24 h in 50% rabbit plasma, which was similar to that of the same liposomes containing 5 mol% PEG-dipalmitoylphosphatidylethanolamine (DPPE) under the identical conditions.