R. Neubert

Structure of stratum corneum lipids characterized by FT-Raman spectroscopy and DSC. I. ceramides

Abstract Fourier transform Raman spectroscopy and differential scanning calorimetry (DSC) were used to study ceramides type IV as a model substance for the ceramides fraction of stratum corneum lipids. The major part of the Raman spectrum consists of bands owing to the alkyl chain, but there are also bands which belong to the head group of the ceramides. The appearance of the conformationally dependent bands indicates the ordered structure of the hydrocarbon chains. The temperature dependence of the conformationally sensitive bands in the CH 2 stretching region (2800–2975 cm −1 ), in the chain C-C stretching region (1050–1150 cm −1 ), and in the low frequency region below 300 cm −1 is used to estimate the degree of order in terms of the relative population of trans and gauche conformers. The C-C stretching modes at 1063 cm −1 and 1130 cm −1 (trans conformation) and the asymmetric CH 2 stretching mode at 2880 cm −1 decrease rapidly near the phase transition temperature and disappear in the liquid state. The temperature and width of the phase transition, derived from Raman data, are similar to these of the DSC study.

Evaluation of drug penetration into human skin ex vivo using branched fatty acids and propylene glycol

The influence of two middle chain methylbranched fatty acids and propylene glycol on the penetration of the highly lipophilic model substance pyrene butyric acid into human skin ex vivo has been investigated. The results obtained were compared with experimental data using oleic acid as standard enhancer. Analogously, liberation studies of pyrene butyric acid into artificial lipid acceptor membranes were performed to evaluate the contribution of vehicle effects to the skin penetration results. It was shown that the fatty acids initially improve the liberation of the model substance which corresponds to an increase in skin penetration. When the penetration process was assessed, the dermal concentration profiles of pyrene butyric acid and propylene glycol were almost the same, strongly indicating a cotransport for the lipophilic model substance. Levels of both pyrene butyric acid and propylene glycol did increase when the vehicles contained fatty acid. Furthermore, there is some indication of a more specific action of oleic acid within the stratum corneum. However, the major effect on the penetration of pyrene butyric acid arises from propylene glycol. It is caused by solvent properties and solvent drag or favoured partition, respectively, into the stratum corneum and the hydrophilic epidermis and dermis which are supposed to be the main diffusion barrier for the model penetrant.

Characterization of interactions between bile salts and drugs by micellar electrokinetic capillary chromatography. Part I.

AbstractPurpose. The general properties of micellar electrokinetic capillary chromatography (MECC) were utilized to characterize the strength of interactions between bile salts and biological active substances.nMethods. For that purpose various bile salts were used as micellar pseudostationary phase in the background electrolyte. Furthermore, a physicochemical model was applied and the effective partition coefficients between micellar and water phase were calculated in order to evaluate the strength of interactions between bile acids and the drugs.nResults. It was found that the interactions between the selected drugs and bile salts depend both on the lipohilicity of the drugs and on the charge of the components. Only hydrophobic, cationic drugs such as quinine and propranolol are able to interact with these surface-active agents.nConclusions. MECC is a valuable methode to characterize interactions such occurring between drugs and bile salts.

Application of capillary zone electrophoresis for analyzing biotin in pharmaceutical formulations—a comparative study

The detection limit and reproducibility of capillary zone electrophoresis (CZE) measurement of biotin were compared to those of a spectrophotometric method and those of the determination of the sulphur content by combustion of the biotin sample followed by coulometric titration of the formed SO2. Drug analysis showed that all three methods gave consistent results and were suitable for the determination of biotin. CZE was found to be the best method for the determination of pharmaceutical formulations containing biotin because of its high separation efficiency, short analysis time, ease of instrumentation and sample preconditioning, and good precision.

Interactions between food components and drugs. Part 4: Influence of pectins and bile salts on propranolol absorption

Abstract Influence of dietary fiber components on drug absorption was studied in vitro using artificial membranes and mucosa preparations from guinea pig in 2-compartment model systems (permeation model and equilibrium dialysis). Well defined pectin preparations with different structural properties were used as food components and propranolol (P) as basic model drug. The retardation of drug was increased with decreased degree of esterification (DE) of pectin. Pectins with a blockwise distribution of free carboxyl groups possessed a more intensive effect than pectins with a random arrangement. It was found that P transport across the artificial lipid membrane was significantly decreased by pectins with a blockwise (DE

Quantitative analysis of drug content in semisolid formulations using step-scan FT-IR photoacoustic spectroscopy

Abstract Step-scan FT-IR photoacoustic spectroscopy in conjunction with a phase modulation technique (modulation frequency of 25 Hz) and digital signal processing was applied in order to quantify the content of brivudin and dithranol in vaseline/drug ointment. The PA spectra of the mixtures exhibit an excellent signal to noise ratio and bands belonging to the drugs are clearly observable down to an 0.5 wt% concentration of the drug. The integrated intensity of the drug bands with reference to a vaseline band was used as a measure of drug content. For comparison, the concentration of drug was determined by capillary zone electrophoresis for brivudin and by HPLC for dithranol. It appears that Beers law is fulfilled for the PAS data. No sample preparation was required for the PAS experiments.

Ceramides/Cholesterol Mixtures as Characterized by FT Raman Spectroscopy

Ceramides IV, hydrated ceramides IV and ceramides/cholesterol mixtures were studied by FT Raman spectroscopy and differential scanning calorimetry (DSC). The temperature-dependence of the conformationally sensitive bands in the CH2 stretching region was used to estimate the degree of order of hydrocarbon chains in terms of the relative population of trans and gauche conformers. The temperature and width of the phase transition, derived from Raman data, are similar to those from the DSC studies. The addition of both cholesterol and water lowers the phase transition temperature and broadens the transition range.

Influence of Ion Pairing on ex vivo Penetration of Erythromycin into Sebaceous Follicles

Microorganisms play an important role in the pathomechanism of acne vulgaris which is treated with antibiotics, particulary erythromycin (ERY). The main problem in the topical use of ERY lies in achieving sufficient penetration of the drug into sebaceous follicles. Doubly enhanced penetration of an ion pair composed of ERY and octadecansulfonate (OS) in contrast to the commonly used ERY base was observed, using a multilayer membrane model (MMM). The aim of the present study was to evaluate the results obtained on the MMM using excised human skin. The amount of ERY penetrating into sebaceous follicles of freshly excised human skin was measured using [N-methyl-14C]erythromycin. The ex vivo penetration of the ion pair ERY/OS into the sebaceous follicles was observed to be doubly enhanced compared with the penetration of the ERY base. The model was shown to be suitable for predicting in vivo penetration of anti-acne formulations into sebaceous glands.

Optimization of Topical Erythromycin Formulations by Ion Pairing

Erythromycin (ERY) is used in the topical treatment of acne vulgaris. In order to decrease the amount of microorganisms markedly, the antibiotic must penetrate into the sebaceous follicles. Firstly, the aim of this study was to improve the lipophilicity of ERY by ion pairing. Secondly, a formulation with optimized penetration of the ion pair was developed. Thirdly, the optimized formulation was compared with formulations containing ethanol and with the commercial product Zineryt. The determination of lipophilicity was based on partition coefficients (PC) and on the penetration of ERY into a modified multilayer membrane system (MMS). It was shown that the penetration of ERY into a lipophilic acceptor system was three times higher when ion pairing between ERY and octadecansulfonate was used in comparison with the penetration of the ERY base alone. The dosage of the antibiotic used can be markedly reduced by optimizing a vehicle for the ion pair.