Formulation of anti-acne concealer containing cinnamon oil with antimicrobial activity against Propionibacterium acnes.

This study aimed to develop an anti-acne concealer containing essential oil with anti-Propionibacterium acnes activity. Antimicrobial activity of cinnamon oil, galangal oil, and eucalyptus oil against P. acnes DMST 14916 was assayed using agar disc diffusion and the broth dilution method. Cinnamon oil showed the maximum inhibitory activity against P. acnes with a clear zone diameter of 36.75 ± 1.06 mm, compared to 14.67 ± 0.58 and 41.83 ± 1.04 mm for tea tree oil and clindamycin, respectively. The minimum inhibitory concentration value of cinnamon oil was 5 mg/mL. Among five formulations of concealer incorporating 0.5% w/w cinnamon oil, F4 provided good texture, coverage, and spreadability with anti-P. acnes activity and stable under determined storage conditions. Cinnamon oil could be a promising cosmetic ingredient for anti-acne products, and F4 concealer may be useful for both covering skin imperfections and the management of acne.

Production of 4-androstene-3,17-dione and 1,4-androstadiene-3,17-dione from rice germ and wheat germ extracts by Mycobacterium sp.

OBJECTIVE: To study the biotransformation of phytosterol and phytosterol-containing rice germ and wheat germ ethanolic extracts to produce 4-androstene-3,17-dione (AD) and 1,4-androstadiene-3,17-dione (ADD) by Mycobacterium sp. DSM 2966 using phytosterol to hydroxypropyl-ß-cyclodextrin (2:1, 1:1 and 1:2 mol/mol) and 2 % (w/v) Tween 80 as solubilizing agents. RESULTS: A maximum yield of 180 ± 27 mg AD l(-1) and 31 ± 11.4 mg ADD l(-1) with a total conversion of 65 % (day 12) was obtained using 1 g phytosterol l(-1) and hydroxypropyl-ß-cyclodextrin (2 : 1 mol/mol) with 2 % (w/v) Tween 80 in the fermentation medium. The most appropriate conditions for rice germ extract and wheat germ extract which gave the maximum conversion of 22 and 43 % (day 14) were obtained by using 2 % (w/v) Tween 80. CONCLUSIONS: Phytosterol and wheat germ are effective sources for AD and ADD production while rice germ required further development. Hydroxypropyl-ß-cyclodextrin (2 :1 mol/mol) and/or 2 % (w/v) Tween 80 in the biotransformation process could improve AD and ADD yields, depending on substrates and biotransformation conditions.

Validation of an HPLC method for determination of pentoxifylline in human plasma and its application to pharmacokinetic study.

An HPLC method suitable for routine determination of pentoxifylline in human plasma has been adapted and validated. Sample preparation was done by solid-phase extraction. Chloramphenicol was used as the internal standard. The linear range was from 15-400 ng/mL (r2 = 0.9994), with a limit of quantitation of 15 ng/mL. The limit of detection was found to be 5 ng/mL. The intra- and interday accuracy ranged from 98.0 to 110.2% and the coefficient of variation was not more than 8.8% for both intra- and interday precision. The absolute recoveries of pentoxifylline and chloramphenicol from human plasma were >97%. The method was validated with excellent specificity, accuracy, precision, recovery, and stability. The pharmacokinetic study of a generic pentoxifylline 400 mg tablet in healthy Thai male volunteers after a single dose administration was determined by this developed assay.

Bioequivalence of generic lamotrigine 100-mg tablets in healthy Thai male volunteers: a randomized, single-dose, two-period, two-sequence crossover study.

BACKGROUND: Lamotrigine is an antiepileptic drug which has been used in the treatment of epilepsy and bipolar disorder. A search of the literature did not find previously published bioequivalence and pharmacokinetic evaluations of lamotrigine in healthy Thai male volunteers. OBJECTIVE: The aim of this study was to compare the pharmacokinetic parameters between 2 brands of lamotrigine in healthy Thai male volunteers. METHODS: A randomized, single-dose, 2-period, 2-sequence, crossover study design with a 2-week washout period was conducted in healthy Thai males. Subjects were randomized to receive either the test or reference formulation in the first period. All subjects were required to be nonsmokers and without a history of alcohol or drug abuse. Plasma samples were collected over a 120-hour period after 100-mg lamotrigine administration in each period. A validated high-performance liquid chromatography ultraviolet method was used to analyze lamotrigine concentration in plasma. Pharmacokinetic parameters were determined using a noncompartmental method. Bioequivalence between the test and reference products, as defined by the US Food and Drug Administration (FDA), is determined when the ratio for the 90% CIs of the difference in the means of the log-transformed AUC(0-t), AUC(0-infinity), and C(max) of the 2 products are within 0.80 and 1.25. Adverse events were determined by measuring vital signs after dosing. Subjects were also asked if they suffered from undesirable effects such as nausea, vomiting, dizziness, and headache. RESULTS: This bioequivalence study was performed in 24 healthy Thai males (mean [SD] age, 20.5 [1.3] years; range, 19-24 years; weight, 62.5 [7.4] kg; height, 172.8 [6.9] cm; body mass index, 20.9 [2.0] kg/m(2)). The mean (SD) C(max) and T(max) of the test formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.2 (0.9) hours, respectively. The mean (SD) C(max) and T(max) of the reference formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.4 (1.0) hours, respectively. The mean (SD) AUC(0-t) was 67.1 (13.2) microg/mL x h(-1) for the test product and 66.4 (14.6) microg/mL x h(-1) for the reference product. The mean (SD) AUC(0-infinity) was 74.9 (18.3) microg/mL x h(-1) for the test product and 74.3 (20.5) microg/mL x h(-1) for the reference product. The mean (SD) t((1/2)) values were 35.0 (7.6) hours for the test product and 34.7 (7.6) hours for the reference product. The mean test/reference ratios for AUC(0-t), AUC(0-infinity), and Cmax were 1.01, 1.01, and 1.05, respectively. The parametric 90% CIs for AUC(0-t), AUC(0-infinity), and Cmax were 0.98 to 1.05, 0.98 to 1.06, and 0.98 to 1.13, respectively. Following administration, dizziness or headache was reported in 2 subjects in the test group and 1 subject in the reference group. CONCLUSION: The results of this study suggest that the test product was bioequivalent to the reference product in these healthy Thai male subjects, based on the US FDA's regulatory definition.

Effect of Bacopa monniera Linn. extract on murine immune response in vitro.

The study was to investigate and compare the effects of the Bacopa monniera Linn. extract and bacoside A on the ICR mice immune system in vitro. Splenocyte proliferation without or with mitogen (lipopolysaccharide, pokeweed mitogen, phytohaemagglutinin and concanavalin A) and phagocytic activity were assayed. The results showed that B. monniera extract at 0.001-1 mg/mL slightly suppressed splenocyte proliferation (SI 0.7) and decreased T-lymphocyte proliferation (SI 0.4) at 0.001 and 0.1 mg/mL with concanavalin A. Bacoside A at 0.001 mg/mL gave the highest splenocyte proliferation (SI 1.5) and strongly increased T-lymphocyte proliferation (SI 2.0) at 0.1 mg/mL with concanavalin A. Thus, it is possible to attribute the effect of B. monniera extract on splenocyte proliferation to the presence of bacoside A with other combined components. However, only B. monniera extract at 10 mg/mL produced a slight increase in lysosomal enzyme activity (PI 1.2), indicating a weak effect on phagocytic activation. It might be concluded that B. monniera manifests various effects on the murine immune system depending on the immune cell types, in accordance with its folklore uses. New assays are being carried out to study its mechanisms and to further investigate its applications in the treatment of human immune mediated diseases.

A simple bioanalytical assay for determination of montelukast in human plasma: application to a pharmacokinetic study.

An analytical method based on high-performance liquid chromatographic (HPLC) was developed for the determination of montelukast in human plasma using mefenamic acid as an internal standard. After precipitation of plasma proteins with acetonitrile, chromatographic separation was carried out using a Zorbax Eclipse XDB C8 (150 mm x 4.6 mm i.d., 5 microm) with mobile phase consisted of methanol-acetonitrile-0.04M disodium hydrogen orthophosphate (22:22:56, v/v, pH 4.9). The wavelengths of fluorescence detection were set at 350 nm for excitation and 450 nm for emission. The linearity was confirmed in the concentration range of 5-1000 ng/ml in human plasma. Intra- and inter-day accuracy determined from quality control samples were 101.50 and 107.24%, and 97.15 and 100.37%, respectively. Intra- and inter-day precision measured as coefficient of variation were < or =4.72 and < or =9.00%, respectively. Extraction recoveries of drug from plasma were >48.14%. The protocol herein described was employed in a pharmacokinetic study of tablet formulation of montelukast in healthy Thai male volunteers.

Comparative study on the bioequivalence of two formulations of pioglitazone tablet in healthy Thai male volunteers.

The bioequivalence study of two 30 mg pioglitazone formulations was determined in healthy Thai male volunteers after a single dose administration in a randomized cross-over study with a 1-week washout period. Due to the high variability of the rate and extent of absorption of pioglitazone, an add-on subject study was required to assess bioequivalence. Reference product Actos, Takeda Chemical Industries, Ltd., Osaka, Japan) and test product (Glubosil, Silom Medical Co. Ltd., Bangkok, Thailand) were given to 35 volunteers after overnight fasting. Blood samples were collected at specified time intervals. Plasma was analyzed for pioglitazone concentration using a validated HPLC method. Pharmacokinetic parameters were compared between test and reference products from plasma concentration-time profile by using non-compartment analysis. The statistical comparison of C(max) and AUC(0-t), AUC(t-infinity) clearly indicated that no significant difference in two products of pioglitazone tablets in add-on subject study. The 90% confidence intervals for the mean ratio (test/reference) of C(max) and AUC(0-t), AUC(t-infinity) were within the Thailand Food and Drug Administration acceptance range. Based on the pharmacokinetic and statistical results of this study, we can conclude that Glubosil is bioequivalent to Actos, and that two products can be considered interchangeable in medical practice.

High-performance liquid chromatographic method for the determination of pioglitazone in human plasma using ultraviolet detection and its application to a pharmacokinetic study.

An analytical method based on high-performance liquid chromatography (HPLC) with ultraviolet detection (269 nm) was developed for the determination of pioglitazone in human plasma. Rosiglitazone was used as an internal standard. Chromatographic separation was achieved with a reversed-phase Apollo C18 column and a mobile phase of methanol-acetonitrile-mixed phosphate buffer (pH 2.6; 10mM) (40:12:48, v/v/v) with a flow rate of 1.2 ml/min. The calibration curve was linear over the range of 50-2000 ng/ml (r(2)>0.9987) and the lower limit of quantification was 50 ng/ml. The method was validated with excellent sensitivity, accuracy, precision, recovery and stability. The assay has been applied successfully to a pharmacokinetic study with human volunteers.

Validation and pharmacokinetic application of a method for determination of doxazosin in human plasma by high-performance liquid chromatography.

A simple high-performance liquid chromatographic method for the determination of doxazosin in human plasma was developed and validated. Prazosin was used as internal standard. After extraction twice with ethyl acetate, chromatographic separation of doxazosin in human plasma was carried out using a reversed-phase Apollo C18 column (250 x 4.6 mm, 5 microm) with mobile phase of methanol-acetonitrile-0.04 m disodium hydrogen orthophosphate (22:22:56, v/v/v) adjusted to pH 4.9 with 0.9 m phosphoric acid and quantified by fluorescence detection operated with an excitation wavelength of 246 nm and an emission wavelength of 389 nm. The lower limit of quantification (LLOQ) of this assay was 1 ng/mL using 500 microL human plasma. Linearity was established over the range 1-25 ng/mL (r2 > 0.9994). The intra- and inter-day accuracy ranged from 90.5 to 104.4% and the coefficient of variation were not more than 8.6% for both intra- and inter-day precision, over the range of the calibration curve. The absolute recoveries of doxazosin and prazosin from human plasma were more than 91%. Doxazosin demonstrated acceptable short-term, long-term and freeze-thaw stability in human plasma. The assay has been successfully applied to plasma sample ana-lysis for pharmacokinetic study.

Bioequivalence evaluation of two formulations of doxazosin tablet in healthy thai male volunteers.

The bioequivalence of two doxazosin 2 mg tablets was determined in 24 healthy Thai male volunteers after one single dose in a randomized cross-over study with a one week washout period. The study was conducted at Faculty of Pharmaceutical Sciences and Health Sciences Research Institute, Naresuan University, Phitsanulok, Thailand. Reference (Cardura, Heinrich Mack Nachf. GmbH & Co. GK, Illertissen, Germany) and test (Dozozin-2, Umeda Co., Ltd., Bangkok Thailand) were administered to volunteers after overnight fasting. Blood samples were collected at specified time intervals and plasma was separated. The validated HPLC method with fluorescence detection was used for quantification of doxazosin in plasma samples. The pharmacokinetic parameters, T(max), C(max), AUC(t), AUC(infinity), T(1/2), lambda(z), Cl and V(d), were determined from plasma concentration time profile of both formulations by using non-compartment analysis. The calculated pharmacokinetic parameters were compared statistically to evaluate bioequivalence between the two brands. The analysis of variance (ANOVA) using log-transformed C(max), AUC(t), and AUC(infinity) did not show any significant difference between two formulations. The point estimates and 90% confidence intervals for C(max), AUC(t) and AUC(infinity) were within the acceptance range (0.80-1.25), satisfying the bioequivalence criteria of the Thailand Food and Drug Administration Guidelines. These results indicate that Dozozin-2 is bioequivalent to Cardura and, thus, may be prescribed interchangeably.

Improvement of doxazosin determination in human plasma using high-performance liquid chromatography with fluorescence detection.

A simple, sensitive, rapid, and reproducible high-performance liquid chromatographic method is developed and validated for the determination of doxazosin in human plasma without a solvent extraction procedure. This method involves plasma protein precipitation using methanol. The structurally related compound prazosin is used as an internal standard. Doxazosin is detected with high sensitivity using spectrofluorimetry. Over the concentration range 0.5-20 ng/mL, the absolute recovery values are all greater than 98%. The method has a quantitation limit of 0.5 ng/mL. The intra- and interday coefficient of variation and inaccuracy values are all less than 8% and 7%, respectively. Therefore, the method has been applied in pharmacokinetic studies of doxazosin.