Presence Of Parabens Research Articles

Ex vivo studies for the passive transdermal permeation and extent of metabolism of methyl and butyl paraben from a cream

Concerns regarding the safety of cumulative exposure to parabens have been raised as a consequence of their estrogenic and endocrine effects. These antibacterial agents are commonly used in food, pharmaceutical and cosmetic products. Preliminary data from animal models has indicated potential links between paraben exposure and various conditions ranging from skin disorders to autism. Oral consumption of parabens is not a cause for concern because they are readily metabolised by the liver and excreted rapidly by the kidney. The presence of parabens in adipose tissue is thought to be due to dermal absorption of parabens where they are incompletely metabolised. Various studies have been performed on paraben absorption; however transdermal permeation of parabens from an emulsion has not been studied to date. In this preliminary study dermal permeation and metabolism across human skin were evaluated for methyl paraben (MP) and butyl paraben (BP) from an emulsion, using Franz Diffusion cell system with analysis by q-ToF (quadrupole time of flight) mass spectrometry. MP was observed to have lower permeation and lower extent of metabolism than BP.

The impact of guest compounds on cyclodextrin aggregation behavior: A series of structurally related parabens

Several studies have demonstrated the presence of aggregates in aqueous cyclodextrin containing solutions. The presence of guest compounds has been shown to influence this cyclodextrin aggregation process. In an attempt to gain insight into the effect of the physicochemical properties of the guest compound on 2-hydroxypropyl-β-cyclodextrin aggregation formation, a series of structurally related parabens was selected as model compounds. Using nuclear magnetic resonance spectroscopy and phase solubility studies, these parabens, differing only in side chain length, were demonstrated to form inclusion complexes with 2-hydroxypropyl-β-cyclodextrin. Additional techniques were subsequently applied to evaluate the aggregation behavior of this cyclodextrin in presence of the selected parabens. Solutions containing a broad range of 2-hydroxypropyl-β-cyclodextrin concentrations were saturated with the guest compounds and were used as test media. Results obtained from dialysis experiments, dynamic light scattering and mass spectrometry revealed a positive effect of the side chain length of the parabens on aggregate formation: in presence of heptylparaben, more and larger aggregates were observed than in presence of parabens with shorter side chains such as methyl- and butylparaben. No clear connection could be demonstrated between the cyclodextrin concentration and the extent of aggregate formation in presence of the guest compound.

Development and Validation of New RP-HPLC Method for Simultaneous Determination of Methyl and Propyl Parabens with Levetiracetam in Pure Form and Pharmaceutical Formulation

A simple and robust high-performance liquid chromatography (HPLC) method is described for the assay for levetiracetam (LTC), methyl paraben (MHB), and propyl paraben (PHB) either in their pure form or in commercial Levepsy® syrup. The method is selective and stability indicating and all chromatographic conditions were studied to obtain adequate separation of LTC, MHB, and PHB from their degradation products and from excipients. The HPLC separation was carried out on a RP C18 Hypersil BDS analytical column (150 mm × 4.6 mm ID) using gradient elution system. The mobile phase flow rate was 1.5 mLmin−1 and the column temperature was kept at 40°C. Complete separation of the studied components was obtained within a cycle time of 8 min. LTC, MHB, and PHB were eluted at 1.56, 5.86, and 7.85 min, respectively. Detection was carried out at 240 nm using a dual wavelength detector. The method has been validated for linearity, accuracy, precision, specificity, limit of detection, limit of quantitation, robustness, and ruggedness. The proposed method was successfully applied for the determination of LTC in the presence of parabens in Levepsy syrup.

Discrete Wavelet Transform-Partial Least Squares Versus Derivative Ratio Spectrophotometry for Simultaneous Determination of Chlorpheniramine Maleate and Dexamethasone in the Presence of Parabens in Pharmaceutical Dosage Form

Purpose: To compare two methods, based on different approaches, for simultaneous determination of chlorpheniramine maleate (CHP) and dexamethasone (DX) in the presence of methyl and propyl paraben in phenadone syrup.Methods: The first method used, based on univariate calibration approach, was first derivative of the ratio spectrophotometry (DD1). The second method, which is a multivariate calibration approach, was discrete wavelet transform followed by partial least squares method (DWT-PLS) which anticipated high predictive ability for the determination of both CHP and DX.Results: DD1 method failed to determine DX due to the absence of adequate zero crossing point while DWT-PLS method was successfully applied for the analysis of raw materials and the dosage form. For DD1 method, recovery of chlorpheniramine maleate in the dosage form was 100.33 ± 0.91 % while for DWT-PLS method, recovery of chlorpheniramine maleate and dexamethasone was 100.24 ± 1.21 and 99.99 ± 1.08 %, respectively. The proposed methods were validated using standard addition technique and the results compared favorably with those obtained by a reference high performance liquid chromatography (HPLC) method.Conclusion: The findings of this work show the superiority of DWT-PLS over DD1 method in solving such complex mixtures, and would thus be suitable for use in quality control (QC) laboratories and pharmaceutical industry.Keywords: Quantitative analysis, Discrete wavelet transform, First derivative of ratio spectra, Chlorpheniramine maleate, Dexamethasone

Development of Three Methods for Simultaneous Quantitative Determination of Chlorpheniramine Maleate and Dexamethasone in the Presence of Parabens in Oral Liquids

Purpose: To develop new selective, precise, and accurate methods for the simultaneous determination of chlorpheniramine maleate (CHP) and dexamethasone (DX) in the presence of methyl and propyl paraben in phenadone syrup.Methods: In the first two methods, the predictive abilities of principal component regression (PCR) and partial least squares (PLS), respectively, were examined for the analysis of the quaternary mixture. The third method, high performance thin layer chromatography (HPTLC)-densitometric method, was based on the separation of the mixture on silica gel plates using chloroform: methanol (93:7, v/v) as a mobile phase.Results: All the proposed methods were successfully applied to the analysis of raw materials and dosage form. For PCR method, recovery of chlorpheniramine maleate and dexamethasone in the dosage form was 98.89 ± 1.736 and 102.36 ± 1.86 %, respectively while for. PLS method, recovery of chlorpheniramine maleate and dexamethasone was 98.94 ± 1.69 and 102.33 ±1.84, respectively. On the other hand, recovery of the two analytes by HPTLC method was 100.72 ± 1.05 and 102.29 ± 3.98, respectively. The results obtained by applying the proposed methods were statistically analyzed and compared with those obtained by a reported HPLC method.Conclusion: The proposed methods are fast, accurate and specific, and can be applied for the quantitative determination of the two analytes without interference from added excipient, thus obviating the need for preliminary extraction of analytes from the pharmaceutical formulation. Thus, they are suitable for use in quality control (QC) laboratories and pharmaceutical industryKeywords: Chlorpheniramine maleate, Dexamethasone, Principal component regression, Partial least squares, High performance thin layer chromatography, Excipients

市販口紅中のパラベン類およびフェノキシエタノール含有量とその摂取量の推定

The presence of parabens and phenoxyethanol (PE) was investigated in 129 types of commercial lipstick products based on the ingredients listed on their labels. 55 products (42.6%) were labelled as containing parabens, and 30 (23.3%) were labelled as containing PE. 50 commercial lipstick tubes were purchased, and the amounts of parabens and PE were assayed using HPLC. Parabens was detected in 43 tubes with an average value of 128mg/100g, and PE was detected in 16 tubes with an average value of 260mg/100g. A questionnaire survey regarding the use of lipstick was conducted among 28 female respondents. Based on the survey results, the quantity of paraben and PE ingested was estimated from their contents in commercial lipsticks. The average quantity of ingested parabens (of the total paraben content) was estimated to be 0.060mg/day, and that of PE was estimated to be 0.12mg/day. The maximum quantity of parabens and PE ingested in one day was estimated to be 0.953mg and 1.25 mg, respectively. Consequently, the paraben and phenoxyethanol daily intakes from commercial lipsticks are low, and it was concluded that they are not likely to present any problem with normal use.

The physical stability of thermally-stressed phospholipid-based emulsions containing methyl, propyl and heptyl parabens as model drugs

The objectives of the studies presented herein was to investigate the mechanisms of emulsion instability under thermal stress (121 °C) by evaluating the effects of a lipophilic drug dissolved in the internal phase of an oil-in-water (o/w) emulsion on growth rate suppression and the apparent microviscosity. Model drugs used were methyl, propyl and heptyl paraben. The o/w emulsions were prepared using medium chain triglycerides as an internal phase in aqueous glycerol solutions emulsified with phospholipids. Concentrations of paraben in the internal phase varied from 0.2–0.8 M. Microfluidization was used to reduce the droplet size to the submicron range. Microviscosity was calculated from the measured anisotropy of a fluorophore probe (1,6-phenyl-1,3,5-hexatriene) using a modified Perrin’s equation. Emulsion aliquots were subjected to thermal stressed at 121 °C the droplet growth rate was determined from periodic measurements of the mean droplet diameter using photon correlation spectroscopy. The growth rate decreased in the presence of parabens. Maximal growth suppression occurred at paraben concentrations of 0.4 M. However in deference to theoretical predictions of the effects of increasing co-solute concentrations based on Ostwalt ripening, the droplet growth rates increased at concentrations greater than 0.4 M. The logarithm of the growth rate was linearly correlated to the interfacial rigidity (inverse microviscosity) of the emulsion which suggests that coalescence rather than molecular diffusion was primarily responsible for emulsion instability under the conditions studied.

Derivative spectrophotometric determination of droperidol in presence of parabens

We have developed a fast and accurate method for the determination of droperidol in the presence of methylparaben and propylparaben using derivative spectrophotometry. The first derivative amplitudes at 255.2 nm were selected for the assay. Calibration graph follows Beer's law in the range of 5–35 μg ml −1. The coefficient of variation (CV) for intra-day and inter-day precision were less than 1.0 and 2.0%, respectively. The method was applied in the quality control of commercial oral and injection solutions and proved to be suitable for routine analysis.

Zero-crossing derivative spectrophotometry for the determination of haloperidol in presence of parabens

First derivative spectrophotometry with a zero-crossing technique of measurement is used for the quantitative determination of haloperidol in the presence of methylparaben and propylparaben, which is added as antimicrobial preservatives in pharmaceuticals. This technique permits the quantification of haloperidol in the presence of parabens, with closely overlapping spectral bands, and without any separation step. Linear calibration graphs of first derivative values (at 255.2 nm for haloperidol) versus concentration (in the range 4.0–20.0 μg ml −1) were obtained with negligible intercepts. Relative standard deviation of 0.83% was obtained for intra-day precision and 1.86% for inter-day precision. The recovery of haloperidol in synthetic mixtures with parabens and in pharmaceutical dosage forms is also reported.

HPLC-Quantification of Diethylamine Salicylate and Methyl Nicotinate in Ointments

Abstract A simple liquid chromatographic method for simultaneous quantification of diethylamine salicylate and methyl nicotinate in the presence of parabens and some drug degradation products is demonstrated. The LC-separation of the two drug substances was undertaken on a column packed with μ-Bondapack C18 using 1% aqueous acetic acid-acetonitrile (85 + 15) at a flow rate of 1.7 ml/min at ambient temperature with detection at 254 nm. Gradient mixing was adopted after 12 min to enhance the rapid elution of the component propyl paraben and other firmly adsorbed ingredients in the ointment base. Good percent assay and mean recoveries with low deviations were obtained for each added drug substance. The stability indicating characteristic of the investigated procedure shows its advantage over another HPLC-method.