Determination of phenolics in cosmetic creams and similar emulsions

A new method for the analysis of phenolics in cosmetic creams has been developed, based on a systematic study of the extractability of five phenolic compounds from such emulsions. A solid-liquid extraction using ultrasound was applied as a prior stage to the chromatographic determination of phenolics in the extracts. Three solvents, hexane, methanol and water, were used as extracting agents. These solvents permit both the de-emulsification of the creams and the extraction of phenolics. A factorial fractional experimental design was developed to analyse the influence in the extraction process of five different extraction variables: ultrasound horn, temperature, extracting volume, cycle and amplitude of ultrasounds. Graphic analysis of results revealed the variables with most influence in the extraction, as well as the interactions between the variables. Finally, the influence of the extraction time and the sample quantity were also studied. With this new method, phenolics can be extracted from silicone-based cosmetic creams in 10 min, using 50 degrees C as extraction temperature. RSDs (n=6) calculated ranged from 1.5% for ferulic acid to 6.5% for epicatechin. Recoveries of between 88.9% for gallic acid and 98.4% for caffeic acid were obtained.     

The application of chromatography to the analysis of pharmaceutical creams

Summary The application of GLC, HPLC and TLC to the analysis of pharmaceutical creams is discussed with special attention to sample clean-up. The results of the determination of hydrocortisone acetate, salicylic acid, benzoic acid, diethyl stilbestrol, chloramphenicol, diphenhydramine HCl, tretinoin and some cream base components by reversed phase HPLC are given.Presented at the 14th International Symposium on Chromatography London, September, 1982     

Determination of methyl nicotinate in pharmaceutical creams by high-performance thin-layer chromatography

Summary A rapid, simple and specific high-performance, thin-layer chromatographic, photodensitometric method is described for the quantitative determination of methyl nicotinate. The HPTLC plates, coated with silica gel, are developed with a mobile phase which allows the separation of several active components in pharmaceutical creams. After quantitation of methyl nicotinate, a second solvent can be used for the identification of the cream base excipients.     

Liquid chromatographic and spectrophotometric determination of diflucortolone valerate and isoconazole nitrate in creams

A new RP-LC method and two new spectrophotometric methods, principal component regression (PCR) and first derivative spectrophotometry, are proposed for simultaneous determination of diflucortolone valerate (DIF) and isoconazole nitrate (ISO) in cream formulations. An isocratic system consisting of an ACE C18 column and a mobile phase composed of methanol-water (95 + 5, v/v) was used for the optimal chromatographic separation. In PCR, the concentration data matrix was prepared by using synthetic mixtures containing these drugs in methanol-water (3 + 1, v/v). The absorbance data matrix corresponding to the concentration data matrix was obtained by measuring the absorbances at 29 wavelengths in the range of 242-298 nm for DIF and ISO in the zero-order spectra of their combinations. In first derivative spectrophotometry, dA/dlambda values were measured at 247.8 nm for DIF and at 240.2 nm for ISO in first derivative spectra of the solution of DIF and ISO in methanol-water (3 + 1, v/v). The linear ranges were 4.00-48.0 microg/mL for DIF and 50.0-400 microg/mL for ISO in the LC method, and 2.40-40.0 microg/mL for DIF and 60.0-260 microg/mL for ISO in the PCR and first derivative spectrophotometric methods. These methods were validated by analyzing synthetic mixtures. These three methods were successfully applied to two pharmaceutical cream preparations.     

Colloidal microstructure of binary systems and model creams stabilized with an alkylpolyglucoside non-ionic emulsifier

The aim of this study was to examine the lyotropic potential of an alkylpolyglucoside mixed emulsifier (Cetearyl glucoside&Cetearyl alcohol), which belongs to the new generation of natural (sugar) surfactants, and to elaborate the potential stabilization mechanism and relation between the colloid microstructure and water distribution within the systems. Polarization and ordinary light as well as transmission electron microscopy, wide and small-angle X-ray diffraction, thermal analysis and rheological measurement were employed for the systems characterization.It was suggested that Cetearyl glucoside&Cetearyl alcohol stabilizes the o/w creams by synergistic effects of viscoelastic hydrophilic gel of lamellar type and lipophilic gel network built up from cetostearyl alcohol semi-hydrates as well as by lamellar liquid crystalline bilayers surrounding the oil droplets. The hydrophilic gel consists of mixed cetearyl glucoside/cetearyl alcohol crystalline bilayers entrapping the water interlamellarly by hydrogen bonding. It is also showed that oil addition into the chosen binary system influences the creams microstructure significantly, which particularly reflects onto the mode of water distribution within the creams and consequently their potential of skin hydration.     

Study of the microstructure of o/w creams with thermal and rheological methods

Thermogravimetric and rheological investigations of oil/water (o/w) creams prepared with different types of surface-active agents (non-ionic, non-ionic POE-free, ionic) were carried out. Thermogravimetry was aimed at the indirect study of the water bond mechanism in o/w creams and the influence of the composition, type and concentration of the mixed emulsifier on the binding of water incorporated in the structure (interlamellar, bulk) and on the binding proportions. The microstructural changes during application were studied with respect to the stability of the lamellar bilayer. This revised version was published online in July 2006 with corrections to the Cover Date.     

Simultaneous determination of bifonazole and tinctures of calendula flower in pharmaceutical creams by reversed-phase liquid chromatography

The aim of this research was to develop and validate a sensitive, rapid, easy, and precise reversed-phase liquid chromatography (LC) method for stability studies of bifonazole (I) formulated with tinctures of calendula flower (II). The method was especially developed for the analysis and quantitative determination of I and II in pure and combined forms in cream pharmaceutical formulations without using gradient elution and at room temperature. The influence on the stability of compound I of temperature, artificial radiation, and drug II used for the new pharmaceutical design was evaluated. The LC separation was carried out using a Supelcosil LC-18 column (25 cm x 4.6 mm id, 5 microm particle size); the mobile phase was composed of methanol-0.1 M ammonium acetate buffer (85 + 15, v/v) pumped isocratically at a flow rate of 1 mL/min; and ultraviolet detection was at 254 nm. The analysis time was less than 10 min. Calibration graphs were found to be linear in the 0.125-0.375 mg/mL (rI = 0.9991) and 0.639-1.916 mg/mL (rII = 0.9995) ranges for I and II, respectively. The linearity, precision, recovery, and limits of detection and quantification were satisfactory for I and II. The results obtained suggested that the developed LC method is selective and specific for the analysis of I and II in pharmaceutical products, and that it can be applied to stability studies.     

Extraction of acyclovir from pharmaceutical creams for HPLC assay. Optimization and validation of pretreatment protocols

Three simple protocols for the extraction of acyclovir from its pharmaceutical creams based on ultrasonication, ultrasonication with heating and magnetic stirring were evaluated and compared. Extraction kinetics were studied at different time intervals (5, 10, 15, 30 and 60 min) and the extraction efficiency was determined by HPLC. The effect of concentration of aqueous NaOH as the extraction medium and the stirring speed were also studied and optimized. Best results were obtained with 50 mL of 0.01 mol L⁻¹ aqueous NaOH with magnetic stirring speed of 500 r.p.m. HPLC analysis involved rapid separation of acyclovir from the cream matrix using a 100 × 4.6 mm i.d. monolithic column and UV detection at 254 nm. Magnetic stirring produced the best results in terms of extraction efficiency with an average extraction yield of 100.8%, n = 16 at an optimum extraction time of 15 min. The selected protocol was validated for within and day-to-day precision and ruggedness.      

High-performance thin-layer chromatography determination of some antimycotic imidazole derivatives and preservatives in medicinal creams and a gel

Simple and reliable thin-layer chromatography-densitometry methods for determination of antimycotics (bifonazole, clotrimazole, and miconazole) and preservatives (benzyl alcohol and benzoic acid) were developed. The pairs bifonazole/benzyl alcohol, clotrimazole/benzyl alcohol, and miconazole/benzoic acid were determined simultaneously. The following mobile phases were used: ethyl acetate-n-heptane-methanoldiethylamine (3 + 4.5 + 1 + 0.2, v/v/v/v) for bifonazole and benzyl alcohol; n-butyl acetate-n-heptane-methanol-dietylamine (3 + 4.5 + 1 + 0.2, v/v/v/v) for clotrimazole and benzyl alcohol; and n-butyl acetate-carbon tetrachloride-methanol-diethylamine (3 + 6 + 2.5 + 0.5, v/v/v/v) for miconazole and benzoic acid. The chromatographic zones on silica gel plates were scanned in the reflectance/absorbance mode at 230 nm (bifonazole, benzyl alcohol, miconazole, and benzoic acid) and 210 nm (clotrimazole and benzyl alcohol). The recovery for all substances ranged from 98.7 to 100.7%. The limits of detection and quantitation were 0.03 to 0.2 microg and 0.1 to 0.5 microg/spot, respectively. The proposed methods were applied for determination of antimycotics and preservatives in commercially available pharmaceuticals.     

Ultrasonic velocity measurements as a method for investigating phase transitions of monoglyceride emulsifier systems in pearlescent cosmetic creams

The phase transitions of monoglyceride emulsifier systems and pearlescent effects in cosmetic creams are investigated using ultrasonic velocity measurements. The transitions between the different phases of monoglyceride emulsifier systems--the coagel, liquid-crystalline lamellar phase, and gel phase--are detected in creams by changes in the ultrasonic velocity with variation of the temperature. The phase transition temperatures correspond to DSC results. Furthermore, the slope of the ultrasound velocity curve correlates with the amount of bound water in the different phases. These insights into the ultrasonic velocity properties of the monoglyceride emulsifier system of creams make it possible to more closely study the pearlescent effect of the coagel. The temperature domain of the short time reversibility of the pearlescence as well as the back-formation time of the coagel can be determined with this method, which enable the optimization of the formulation of pearlescent creams.     

X-ray investigation of the role of the mixed emulsifier in the structure formation in o/w creams

The aim of this research work was to clarify the role of the mixed emulsifier in the structure formation and water binding mode in the case of o/w creams prepared with different surfactants. The swelling behavior of mixed emulsifiers was examined by means of direct investigation methods such as transmission electron microscopy (TEM) and X-ray diffraction. The detailed structure image of the creams was created with the help of the latter. The influence of the structure of the hydrophilic gel phase, and the structural changes during storage were studied with rheological methods. On the basis of the results, it can be stated that the investigated creams had different structures from those mentioned in the literature: surfactant did not create a mixed bilayer with the structure to furnish fatty amphiphile; instead, micelles were formed. These results correlated well with the results of the rheological tests.     

Fast and sensitive high performance liquid chromatography analysis of cosmetic creams for hydroquinone, phenol and six preservatives

A fast and sensitive HPLC method for analysis of cosmetic creams for hydroquinone, phenol and six preservatives has been developed. The influence of sample preparation conditions and the composition of the mobile phase and elution mode were investigated to optimize the separation of the eight studied components. Final conditions were 60% methanol and 40% water (v/v) extraction of the cosmetic creams. A C18 column (100 mm × 2.1 mm) was used as the separation column and the mobile phase consisted of methanol and 0.05 mol/L ammonium formate in water (pH=3.0) with gradient elution. The results showed that complete separation of the eight studied components was achieved within 10 min, the linear ranges were 1.0-200 μg/mL for phenol, 0.1-150 μg/mL for sorbic acid, 2.0-200 μg/mL for benzoic acid, 0.5-200 μg/mL for hydroquinone, methyl paraben, ethyl paraben and propyl paraben, butyl paraben, and good linear correlation coefficient (≥0.9997) were obtained, the detection limit was in the range of 0.05-1.0 μg/mL, the average recovery was between 86.5% and 116.3%, and the relative standard deviation (RSD) was less than 5.0% (n=6). The method is easy, fast and sensitive, it can be employed to analyze component residues in cosmetic creams especially in a quality control setting.     

Stability-indicating LC assay for butenafine hydrochloride in creams using an experimental design for robustness evaluation and photodegradation kinetics study

A stability-indicating liquid chromatography method for the determination of the antifungal agent butenafine hydrochloride (BTF) in a cream was developed and validated using the Plackett-Burman experimental design for robustness evaluation. Also, the drug photodegradation kinetics was determined. The analytical column was operated with acetonitrile, methanol and a solution of triethylamine 0.3% adjusted to pH 4.0 (6:3:1) at a flow rate of 1 mL/min and detection at 283 nm. BTF extraction from the cream was done with n-butyl alcohol and methanol in ultrasonic bath. The performed degradation conditions were: acid and basic media with HCl 1M and NaOH 1M, respectively, oxidation with H(2)O(2) 10%, and the exposure to UV-C light. No interference in the BTF elution was verified. Linearity was assessed (r(2) = 0.9999) and ANOVA showed non-significative linearity deviation (p > 0.05). Adequate results were obtained for repeatability, intra-day precision, and accuracy. Critical factors were selected to examine the method robustness with the two-level Plackett-Burman experimental design and no significant factors were detected (p > 0.05). The BTF photodegradation kinetics was determined for the standard and for the cream, both in methanolic solution, under UV light at 254 nm. The degradation process can be described by first-order kinetics in both cases.