Ethyl Myristate Research Articles

Prediction of vapor–liquid equilibria for supercritical alcohol + fatty acid ester systems by SRK equation of state with Wong–Sandler mixing rule based on COSMO theory

Vapor–liquid equilibria for supercritical alcohol + fatty acid ester systems were predicted by Soave–Redlich–Kwong (SRK) equation of state with the Wong–Sandler (WS) mixing rules based on an activity coefficient model by Conductor-like Screening Model (COSMO) theory. The predicted systems were methanol + methyl laurate, methanol + methyl myristate, ethanol + ethyl laurate, and ethanol + ethyl myristate systems from 493 to 543 K, near the critical temperatures of methanol ( T c = 512.6 K) and ethanol ( T c = 513.9 K). The excess Gibbs free energies for the mixing rule were determined from the COSMO-Segment Activity Coefficient (COSMO-SAC) model. The universal parameters in COSMO-SAC model were determined by fitting vapor–liquid equilibrium data for alcohol + alkyl acetate systems at low pressures. Predictions for the liquid phase by SRK/WS/COSMO-SAC reproduced the experimental data more accurately than calculations made with SRK/WS/UNIFAC.

Ethanol Contamination Leads to Fatty Acid Ethyl Esters in Hair Samples

The diagnosis of alcoholism is a topical subject of discussion; in fact, many studies have been published on the determination of biochemical markers useful to this target. Fatty acid ethyl esters (FAEE) are minor metabolites of ethanol, and their usefulness has been demonstrated by their detection in hair using a headspace solid-phase microextraction-gas chromatographic-mass spectrometric technique. Environmental contamination in the analysis of drugs of abuse is a well-known focus of discussion between scientists. In the same way, interference from the surroundings could be hypothesized in FAEE detection. To assess the influence of ethanol contamination, an in vitro experiment was performed, leaving hair in an atmosphere saturated with ethanol vapors for 15 days. The spontaneous production of FAEE was demonstrated by analyzing hair day by day. In fact, we observed a constant increase of ethyl myristate, palmitate, and stearate that reached very high concentrations at the end of the investigation. Although the experiment was managed in a stressed way and could not represent real life, its purpose was to focus the attention of researchers on the problem of hair contamination that can occur, for example, with ethanol-containing cosmetics. Therefore, care in interpretation must be taken into account, especially with such a volatile molecule.

Behaviour of some volatile compounds during distillation of fermented marc exposed to the smoking process

SummaryFermented marc was exposed to a controlled smoking process for 120, 240 and 460 min before distillation. To improve insight into the behaviour of ethanol and the partitioning of some volatile compounds, each distillate was collected in fractions (ethanol content from 24 to 59% vol) and analysed for the higher alcohols (2‐butanol, n‐butanol, n‐propanol, isoamyl alcohols, n‐hexanol) ethyl esters (ethyl acetate, ethyl lactate, ethyl caproate, ethyl caprylate, ethyl caprate, ethyl myristate and ethyl laurate) and volatile phenols (guaiacol, methyl guaiacol, ethyl guaiacol, propyl guaiacol, eugenol and isoeugenol). The results obtained showed that the behaviour of ethanol was not regular and the alcohol strength was lower when the smoking process was applied to fermented marc. The volatile phenols highlighted a distillation behaviour characterised by an increase in concentration at the end of the distillation process when ethanol decreased. Long time exposure of the marc to the smoking process resulted in higher reduction of ethanol, higher alcohols and ethyl esters. Instead, the volatile phenols increased with the duration of the smoking process.

Measurement and correlation of vapor–liquid equilibria for ethanol + ethyl laurate and ethanol + ethyl myristate systems near critical temperature of ethanol

The vapor–liquid equilibria for ethanol + ethyl laurate and ethanol + ethyl myristate systems were measured by flow method at 493–543 K and 2.11–7.09 MPa, near the critical point of ethanol ( T c = 513.9 K, p c = 6.15 MPa). The mole fractions of ethanol in vapor phase are close to unity at the pressures lower than 6.0 MPa and 493–543 K. It was found that the saturated liquid lines are almost the same for both ethanol + ethyl ester systems. These vapor–liquid equilibria were compared with those for methanol + methyl laurate and methyl myristate systems. The phase behavior was discussed in point of the kinds of alcohol and fatty acid alkyl ester. The experimental data in this work were correlated with Peng–Robinson equation of state. A conventional and Wong–Sandler mixing rules were adopted for the energy and size parameters in the equation of state. The correlated results represent the experimental data in the absolute deviations for the mole fractions of ethanol in vapor and liquid phases, 0.012 and 0.010 with the conventional mixing rule, and 0.005 and 0.036 with Wong–Sandler mixing rule.

Preparation of Cyclosporin A-loaded Nanoparticles Containing Ethyl Myristate or Chitosan and Pharmacokinetics in Rats

An oil-in-water solvent evaporation method was used to prepare the cyclosporin A (CyA)-loaded nanoparticles varying in poly (D,L-lactide-co-glycolide) (PLGA) polymer (RG 502H, RG 503H) and the amount of additive ethyl myristate (EM) or chitosan (CS). The particles were characterized for drug loading and entrapment efficiency by HPLC, surface morphology by scanning electron microscopy, particle size by dynamic light scattering and surface charge by Zetapotential. The results showed drug loadings ranging from 10.9% to 15.8% with high encapsulation efficiency (82.0-97.8%). SEM and DLS studies showed discrete and spherical particles with smooth surfaces and mean size ranging 257.6-721.7 nm. The additive EM or CS did not change the mean sizes of the nanoparticles, whereas by the coating effect of CS, the Zetapotential values of the CS-added nanoparticles were moved to the more positive direction as the amount of CS was increased. From the pharmacokinetic analysis, the nanoparticles formulations showed the higher bioavailability and MRT than While little adding effect of EM or CS was detected in pharmacokinetic profile when RG 503H was used as polymer carrier, more noticeable different pharmacokinetic behaviors could be observed in case of RC 502H. EM incorporation was found to elevate the , whereas CS coating resulted in the decrease of F and , which seems to be due to the function of CS as a barrier and a mucoadhesive coating.

Determination of Some Beer Flavours by Stir Bar Sorptive Extraction and Solvent Back Extraction

J. Inst. Brew. 113(2), 154–158, 2007 This work presents the development of a simple, rapid and low cost method for the determination of some beer flavours as esters such as isoamyl acetate, ethyl caproate, ethyl caprylate, phenyl acetate, ethyl caprate, phenylethyl acetate, ethyl laurate, ethyl myristate and ethyl palmitate using stir bar sorptive extraction (SBSE). The combination of this extraction technique with solvent back extraction and subsequent gas chromatographic analysis with flame ionisation detection was used for the determination of these compounds. The effects of different mixtures of organic solvents and the influence of sampling time and time of solvent back extraction were studied. An optimum procedure for the SBSE method was developed. The method had high repeatability (RSD 2.1–7.3%), good linearity (the correlation coefficients were higher than 0.9995 for quadratic fit over the concentration range from 0.015 to 30 mg/L) and acceptable recoveries (78–107%) and precision (RSD < 7.3%).

Investigation of fatty acid esters to replace isopropyl myristate in the sterility test for ophthalmic ointments

Several pharmacopoeias recommend the membrane filtration method for the sterility test of ophthalmic ointments. Isopropyl myristate, a fatty acid ester that exhibits high toxicity mainly against Gram-negative microorganisms, is indicated as a solvent for ointments. In this study, six fatty acid esters (diethyl adipate, diisopropyl adipate, ethyl laurate, ethyl myristate, methyl caprylate and isopropyl palmitate) were evaluated as solvents to replace isopropyl myristate in the sterility test for ophthalmic ointments. The logarithm of the partition coefficient (log P) of the fatty acid esters was calculated from the sum of the substituent hydrophobicity constants ( π) of the functional groups present in their molecules. The ability of the solvents to dissolve an ophthalmic ointment base was investigated. The D-value method was used to assess the antimicrobial activity of isopropyl palmitate, ethyl myristate, ethyl laurate and isopropyl myristate against Pseudomonas aeruginosa. Isopropyl palmitate was the least toxic solvent to this microorganism, since it had the highest D-value (171.1 min). No significant difference was observed between the D-values of ethyl myristate (89.4 min) and isopropyl myristate (92.5 min). Ethyl laurate exhibited the lowest D-value (27.2 min). Using gas chromatography coupled to mass spectrometry, other fatty acid esters were detected as the predominant impurities in the solvents, as well as acid contaminants in low or insignificant amounts.

Activity coefficient at infinite dilution, azeotropic data, excess enthalpies and solid–liquid-equilibria for binary systems of alkanes and aromatics with esters

Binary azeotropic data have been measured at different pressures for ethyl acetate + heptane, methyl acetate + heptane, isopropyl acetate + hexane and isopropyl acetate + heptane by means of a wire band column. Additionally activity coefficients at infinite dilution have been determined for ethyl acetate and isopropyl acetate in decane and dodecane in the temperature range between 303.15 and 333.15 K with the help of the dilutor technique. Furthermore excess enthalpies for the binary systems methyl acetate + hexane, methyl acetate + decane, ethyl acetate + hexane and ethyl acetate + decane at 363.15 and 413.15 K have been studied with the help of isothermal flow calorimetry. Finally solid–liquid equilibria for the systems ethyl myristate + benzene and ethyl myristate + p-xylene have been investigated by a visual technique. All these data have been used for the revision and extension of the group interaction parameters of the group contribution method modified UNIFAC (Dortmund) and the group contribution equation of state VTPR. The experimental data was compared with the results predicted using the group contribution method modified UNIFAC (Dortmund) and the group contribution equation of state VTPR.

Comparison of ethyl glucuronide and fatty acid ethyl ester concentrations in hair of alcoholics, social drinkers and teetotallers

In previous investigations hair analysis for ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEE) proved to be suitable for the detection of excessive alcohol consumption. The aim of this study was to compare EtG and FAEE concentrations in hair of alcoholics, social drinkers and teetotallers. Hair samples from 10 alcoholics in withdrawal treatment, 11 fatalities with documented excessive alcohol consumption, four moderate social drinkers who consumed up to 20 g ethanol per day, and three strict teetotallers were analysed. After external degreasing with n-heptane, extraction with a dimethyl sulfoxide/ n-heptane mixture and headspace solid-phase microextraction of the extracts, four fatty acid ethyl esters (FAEEs) (ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate) were analysed by gas chromatography–mass spectrometry (GC–MS) with deuterated internal standards. EtG was determined by GC–MS/NCI after ultrasonication of the samples with H 2O, cleanup by SPE with aminopropyl columns and PFP derivatisation. The following concentrations were measured for the four groups: teetotallers EtG < 0.002 ng/mg, FAEE 0.05–0.37 ng/mg, moderate social drinkers EtG < 0.002 ng/mg, FAEE 0.26–0.50 ng/mg, alcoholic patients EtG 0.030–0.415 ng/mg, FAEE 0.65–20.50 ng/mg and the fatalities with alcohol history EtG 0.072–3.380 ng/mg, FAEE 1.30–30.60 ng/mg. The results confirm that by using a cut-off value of the sum of FAEE > 1 ng/mg and/or a positive EtG result in hair, excessive alcohol consumption can be identified using hair analysis. However, no significant correlation between the EtG and FAEE concentrations in the positive cases could be shown. Segmental analysis of some of the specimens did not reveal the same distribution for EtG compared to FAEE in hair, and no chronological accordance compared to the self-reported alcohol consumption could be observed for both parameters. These different results of both methods are discussed in terms of differences between EtG and FAEE in mechanism of formation and incorporation into hair and elimination from hair.

Squalene in hair—a natural reference substance for the improved interpretation of fatty acid ethyl ester concentrations with respect to alcohol misuse

Fatty acid ethyl esters (FAEE) are incorporated into hair mainly from sebum. For this reason, the use of their concentration C FAEE as marker of excessive alcohol consumption is complicated by interindividual differences of the activity of the sebum glands and of elimination by hair care and hair cosmetics. Furthermore, an influence of the investigated hair length due to increasing accumulation from proximal to distal was found. Therefore, it was examined whether these sources of error can be avoided if in addition to C FAEE the relative FAEE concentrationa C FAEE/ C SQ related to squalene SQ as a natural reference compound were used for interpretation. Sebum containes about 10–20% SQ. A sensitive and reliable method for the determination of SQ in addition to FAEE from the same hair extracts by high performance liquid chromatography with photo diode array detector (HPLC-DAD) was developed. The concentrations of ethyl myristate, ethyl palmitate, ethyl oleate, ethyl stearate and squalene were determined and C FAEE/ C SQ was calculated for 13 teetotallers, 16 social drinkers, 12 fatalities with excessive alcohol abuse at life time and 9 cases with unclear alcohol anamnesis. C SQ ranged from 0.02 to 1.97 μg/mg (mean 0.67 μg/mg). From the results follows that squalene enables a control of the lipid content of hair and a correction of C FAEE in cases with deviations from the usual lipid content in a similar way as creatinine in urine. Preliminary values of C FAEE/ C SQ were suggested for the upper limit for teetotallers (< 0.6 ng/μg) and the lower limit for excessive alcohol abuse (> 1.5 ng/μg). However, the relative concentration C FAEE/ C SQ cannot completely replace the absolute concentration C FAEE, and both should regularly be used for an improved interpretation with respect to alcohol abuse.

Wipe-test and patch-test for alcohol misuse based on the concentration ratio of fatty acid ethyl esters and squalene CFAEE/ CSQ in skin surface lipids

Fatty acid ethyl esters (FAEE) are known to be formed in blood and almost all human tissues after alcohol consumption and to be incorporated from sebum into hair where they can be used as long-term markers for excessive alcohol consumption. In order to examine whether skin surface lipids which consist mainly of sebum are an equally useful matrix for measurement of FAEE as alcohol abuse markers, samples were collected by a wipe-test from the forehead of 13 teetotallers, 16 social drinkers, 10 death cases with known recent alcohol misuse and five death cases without indications of alcohol misuse. The samples were analysed by headspace solid-phase microextraction and gas chromatography–mass spectrometry for ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate and by high performance liquid chromatography with photodiode array detector for squalene, (SQ), as a natural reference substance which the FAEE concentrations were related to. The ratio m FAEE/ m SQ ranged between 0.16 and 1.12 ng/μg (mean 0.34 ng/μg) for the teetotallers and between 0.08 and 0.94 ng/μg (mean 0.37 ng/μg) for the social drinkers with no significant difference between both groups. For the alcoholics 2.4–24.2 ng/μg (mean 13.1 ng/μg) were found. For two volunteers the course of m FAEE/ m SQ 2 weeks before and 3 weeks after a single high alcohol dose was pursued by daily wipe tests. A strong increase of m FAEE/ m SQ occurred between 7 and 12 days after the drinking event. This delay can be explained by the transition time of about 8 days between sebum production and its appearance on the skin surface known from literature. For seven social drinkers skin surface lipid samples were also collected using drug of abuse patches of the firm PharmCheck. The ratios m FAEE/ m SQ in these samples were in the same range as from the wipe-test. The comparison with the self-reported ethanol amounts consumed the week before and during the test gave no good correlation ( R 2 = 0.42). It can be concluded from the results that FAEE in skin surface lipids can be used for medium-term retrospective detection of heavy drinking.

New Methods for Neonatal Drug Screening

After completing this article, readers should be able to: 1. Describe perinatal and neonatal complications of maternal use of cocaine, alcohol, opiates, and barbiturates in pregnancy. 2. List established cutoffs of conventional immunoassays of urine for common substances of abuse. 3. List the advantages of using meconium testing for substances of abuse. 4. Describe the role of fatty acid ethyl esters in detecting prenatal alcohol exposure. Maternal substance use during pregnancy can have direct consequences on both the developing fetus and the mother and is a significant public health concern. The prevalence of gestational use of drugs of abuse varies, depending on the study population and method of detection, but it generally ranges from 1% to 15%. (1) One of the largest epidemiologic studies conducted in the United States documented that although most pregnant women decrease the use of substances as the pregnancy progresses, a significant proportion of them remain regular users, even in the third trimester (eg, ethanol [13%], cannabis [9.3%], cocaine [10%], and heroin [1%]). (2) Various perinatal and neonatal complications can result from prenatal exposure to common drugs of abuse. (3) The use of cocaine during pregnancy is associated with increased risks of preterm labor, intrauterine growth retardation, and neurobehavioral abnormalities. Heavy alcohol use during pregnancy leads to fetal alcohol spectrum disorder, which is characterized by an array of congenital malformations, central nervous system abnormalities, and neurodevelopmental deficits. Neonates exposed to opiates, alcohol, and barbiturates in utero are at risk of developing neonatal abstinence syndrome, which is characterized by irritability, gastrointestinal dysfunction, respiratory distress, and other nonspecific symptoms. (1) Data in the literature conflict regarding adverse events in the immediate postnatal period that can be attributed to prenatal exposure to other illicit drugs. Thus, early identification of neonates in whom substance exposure is suspected is important for appropriate treatment intervention and …

Fatty Acid ethyl esters in scalp, pubic, axillary, beard and body hair as markers for alcohol misuse.

This study examined the possibility of using hair samples other than scalp hair for analysis of fatty acid ethyl esters (FAEE) as markers for alcohol misuse. Samples of scalp and pubic hair and, if available, axillary, beard and body hair of one teetotaller, five moderate social drinkers and 22 fatalities were analysed for FAEE by head-space solid-phase microextraction and gas chromatography-mass spectrometry. The sum of the concentrations of ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate (C(FAEE)) in the hair samples was compared with information about the drinking behaviour of the individuals. Although there were large differences in the analyte concentrations in hair from different sites in the same individual, cases of chronic excessive alcohol consumption were characterized by C(FAEE) > 1.0 ng/mg in almost all samples. FAEE concentrations in hair other than scalp hair can be used as markers of chronic alcohol misuse.

Effect of hair care and hair cosmetics on the concentrations of fatty acid ethyl esters in hair as markers of chronically elevated alcohol consumption

Fatty acid ethyl esters (FAEE) can be used as alcohol markers in hair. It was investigated in this study whether this diagnostic method is disturbed by hair care and hair cosmetics. Traces of ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate were detected in all of 49 frequently applied hair care products by headspace solid phase microextraction (HS-SPME) and gas chromatography–mass spectrometry (GC–MS). The highest concentration was 0.003% in a hair wax. From experiments with separated hair samples of alcoholics as well as from the evaluation of the FAEE concentrations and the data about hair care of 75 volunteers (alcoholics, social drinkers and teetotalers) follows that usual shampooing, permanent wave, dyeing, bleaching or shading are of minor importance as compared to the drinking amount and other individual features. However, false positive results were found after daily treatment with a hair lotion containing 62.5% ethanol, with a deodorant and with a hair spray. As an explanation, it is assumed that FAEE are formed in the sebum glands also after regular topical application of products with a higher ethanol content.

Investigation of the factors influencing the release rates of cyclosporin A-loaded micro- and nanoparticles prepared by high-pressure homogenizer

An oil-in-water solvent evaporation method was used to prepare cyclosporin A (CyA)–loaded particles varying in size (nanoparticles, ‘small-sized’ microparticles, ‘large-sized’ microparticles), polymer compositions [poly( d, l-lactide-co-glycolic acid) (PLGA) 50/50, PLGA 85/15, poly( d,l-lactic acid) (PLA)] and additive fatty acid ester (ethyl myristate; EM). The particles were characterized for drug loading and entrapment efficiency by high-performance liquid chromatography, particle size by dynamic light scattering and surface morphology by scanning electron microscopy (SEM). In vitro release kinetics were studied using a modified dialysis method. The results showed drug loadings ranging from 6.48 to 9.01% with high encapsulation efficiency (71.2–98.9%). SEM studies showed discrete and spherical particles with smooth surfaces, whereas rather gross surface defects resulted from the incorporation of EM as an additive. The release profiles of various formulations approximated zero-order release kinetics in the first 3 weeks with a negligible initial burst. In general, the smaller the particle size and the higher the glycolic acid content in the copolymer, the faster the release of CyA. The effect of EM on the release profile appeared to be rather complex since an increased release rate was observed from EM containing PLGA 50/50 particles, whereas the incorporation of EM into the PLGA 85/15 and PLA particles led to a decreased release rate. Further investigation needs to be performed to elucidate the reason why EM influences the CyA release differently depending on the particle size and polymer type.

Fatty Acid Ethyl Esters in Hair as Markers of Alcohol Consumption. Segmental Hair Analysis of Alcoholics, Social Drinkers, and Teetotalers

Fatty acid ethyl esters (FAEEs) are products of nonoxidative ethanol metabolism. After incorporation in hair, they should be suitable long-term markers of alcohol abuse. Hair samples from 19 alcoholics in a treatment program, 10 fatalities with verified excessive alcohol consumption, 13 moderate social drinkers who consumed up to 20 g ethanol/day, and 5 strict teetotalers were analyzed in 1-12 segments for four FAEEs (ethyl myristate, ethyl palmitate, ethyl oleate, and ethyl stearate) by external degreasing with n-heptane, extraction with a dimethyl sulfoxide-n-heptane mixture, headspace solid-phase microextraction of the extracts, and gas chromatography-mass spectrometry with deuterated internal standards. The n-heptane washings were analyzed in the same way for FAEEs from the hair surface. The sum of the four ester concentrations in hair calculated for the proximal 0-6 cm segment was 2.5-13.5 ng/mg (mean, 6.8 ng/mg) for the fatalities, 0.92-11.6 ng/mg (mean, 4.0 ng/mg) for 17 of the alcoholics in treatment, 0.20-0.85 ng/mg (mean, 0.41 ng/mg) for the moderate social drinkers, and 0.06-0.37 ng/mg (mean, 0.16 ng/mg) for the teetotalers. In almost all cases the segmental concentrations increased from proximal to distal. There was no agreement between the self-reported drinking histories of the participants and the FAEE concentrations along the hair length. Ethyl oleate was the dominant ester in all samples. FAEEs are deposited in hair mainly from sebum. Despite large individual differences, FAEE hair concentrations can be used as markers for excessive alcohol consumption with relatively high accuracy.

Analysis of fatty acid ethyl esters in hair as possible markers of chronically elevated alcohol consumption by headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS)

Fatty acid ethyl esters (FAEE) are products of the nonoxidative ethanol metabolism, which are known to be detectable in blood only about 24 h after the last alcohol intake. After deposition in hair they should be suitable long-term markers of chronically elevated alcohol consumption. Therefore, a method for the analysis of ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate from hair was developed based on the extraction of the hair sample by a dimethylsulphoxide (DMSO)/ n-hexane mixture, separation and evaporation of the n-hexane phase and application of headspace solid-phase microextraction (HS-SPME) in combination with gas chromatography-mass spectrometry (GC-MS) to the extract. For use as internal standards, the corresponding D 5-ethyl esters were prepared. The HS-SPME/GC-MS measurements were automatically performed using a multi-purpose sampler. The detection limits of the FAEE were between 0.01 and 0.04 ng/mg and the reproducibility was between 3.5 and 16%. By application of the method to hair samples of 21 fatalities with known heavy alcohol abuse 0.045–2.4 ng/mg ethyl myristate, 0.35–13.5 ng/mg ethyl palmitate, 0.25–7.7 ng/mg ethyl oleate and 0.05–3.85 ng/mg ethyl stearate were measured. For social drinkers (30–60 g ethanol per week), the concentrations were about one order of magnitude smaller. For 10 teetotalers negative results or traces of ethyl palmitate were found. It was shown by supplementary investigations in single cases that FAEE are also present in sebum, that there is no strong difference in their concentrations between pubic, chest and scalp hair, and that they are detectable in hair segments after a 2 months period of abstinence. From the results follows that the measurement of FAEE concentrations in hair is a useful way for a retrospective detection of alcohol abuse.

Lipase-catalysed synthesis of natural ethanol esters: effect of water removal on enzyme reutilisation

Lipase-catalysed synthesis of ethanol esters using natural substrates is presented. Initial substrate concentrations, optimised through an experimental design, were 0.8 mol dm−3 lauric acid and 0.58 mol dm−3 ethanol, with an initial esterification rate (r0) of 17.13 mmol dm−3 min−1. Two different water removal systems were compared: a cooling exchanger in the reactor headspace and a vacuum-based system. The best results were obtained with the second system. After six consecutive operations with the same enzyme, no loss of activity was observed. The yields obtained in all the runs were greater than 90%. Using the same approach three different natural esters (ethyl laureate, ethyl myristate and ethyl palmitate) were synthesised at 0.9 dm3 scale. Similar results were obtained in all three cases, with chemical yields always being greater than 90%. © 2000 Society of Chemical Industry

Modification of release rates of cyclosporin A from polyl( L-lactic acid) microspheres by fatty acid esters and in-vivo evaluation of the microspheres

Biodegradable microspheres containing cyclosporin A (CyA, cyclosporine) were prepared using poly( L-lactic acid) (PLA) and poly(lactide-co-glycolide)(PLGA) by a solvent evaporation method. CyA was efficiently entrapped in PLA, PLGA(50/50) and PLGA(75/25) microspheres in a range of 81–85%. CyA released constantly from PLA microspheres without any lag time, whereas the drug from PLGA(50/50) and PLGA(75/25) microspheres was released after lag time of about 1 and 3 weeks, respectively. Addition of fatty acid esters enhanced the release rates of CyA from PLA microspheres. In-vivo study was performed using rats with adjuvant-induced arthritis. PLA microspheres with ethyl myristate sustained high blood levels of CyA compared with the microspheres with no additives over 4 weeks. In addition, the PLA microspheres improved the symptoms such as the decrease in body weight and the increase in paw swelling occurred by adjuvant-induced arthritis in rats. Consequently, the release rate of CyA from PLA microspheres can be improved by adding fatty acid esters and PLA microspheres with fatty acid esters seem to be a useful dosage form for autoimmune disease therapy.

難水溶性薬物封入ポリ乳酸マイクロスフェアの新規調製法とその放出性

Polylactic acid (PLA) microspheres containing theophylline as a slightly soluble representative drug were prepared using the o/w emulsion in-water drying method. A high trapping efficiency was observed when polymer solution of high concentration was used and the drug/polymer weight ratio was increased. However, the particle size of the microspheres became extremely large when the high concentration polymer solution was used.Microspheres with a particle size of 88.6 μm were obtained when “ sub-emulsification” was performed with the external aqueous phase with an equal specific gravity to the polymer solution. On the other hand, the trapping efficiency of the microspheres was dependent on both the drug encapsulated in the microspheres and the particle size of microspheres.The release patterns of the drug from the microspheres showed an initial-burst release in all batches. The release rates of the drug from the microspheres prepared with the drug and polymer alone were very small. Therefore, an improvement in the drug release property of the microspheres was examined.The release rates of the drug from the microspheres increased si gnificantly depending on the amount of ethyl myristate that was incorporated as a release promoter.