Penetration of compounds through human stratum corneum as studied by Fourier transform infrared photoacoustic spectroscopy.

The penetration of the lipophilic model permeant, 1-cyanodecane, into isolated human stratum corneum (SC) was followed nondestructively by step-scan Fourier transform infrared (FTIR) photoacoustic spectroscopy (PAS) with phase modulation technique. The uptake of the compound in the SC was quantified by monitoring the alterations in the spectra in the course of the penetration using multivariate analysis. Step-scan technique in conjunction with phase modulation offers the possibility for controllable depth profiling (sampling depth up to 30 microm) during the penetration process. Based on Fick's second law and assuming a virtually layered structure of the membrane, depth-dependent diffusion coefficients were derived by numerical fitting of the spectroscopic data. For 1-cyanodecane, the diffusion coefficient in the inner region of the SC is 1.6-fold that measured in the outer region.

Investigation of drug release from suspension using FTIR-ATR technique: part I. Determination of effective diffusion coefficient of drugs.

Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy was used to study directly the release of drug particles (ketoconazole) in a liquid medium (paraffinum liquidum). In the case of the release experiment, the formulation is placed on the ATR crystal and the acceptor membrane on the top of the ointment. The decrease of the drug content in the sediment near the interface ATR crystal-formulation in the course of the release process was quantified by monitoring the changes of the IR spectrum in relevant spectral ranges using multivariate analysis. A mathematical model based on Fick's second law with appropriate initial and boundary conditions was applied in order to determine the diffusion coefficient of the drug in the liquid medium. Knowing this value, it is possible to calculate the effective diffusion coefficient of the drug in heterogeneous semisolid formulation (Vaseline) as a function of the volume fraction of the solid phase.

Investigation of drug release from suspension using FTIR-ATR technique: part II. Determination of dissolution coefficient of drugs.

Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy was applied to a release experiment in order to determine the dissolution coefficient of drug particles in heterogeneous semisolid formulations. The drug release experiment was carried out using ketoconazole suspended in Vaseline with various amounts of paraffinum liquidum as donor and an artificial dodecanol-collodion (DDC) membrane as acceptor compartment. Monitoring changes in IR bands due to ketoconazole the decrease of the drug content near the ATR crystal ointment was followed as a function of time. A mathematical model based on Fick's second law with a source term was used to derive the apparent dissolution coefficient Kdis by numerical fitting the experimental data. It was found that Kdis is dependent on the fraction of paraffinum liquidum in the suspension. Taking into account all experimental parameters required, the transport process was simulated and discussed in terms of drug concentration- time and drug concentration- distance profiles. Calculating the area under the mass-time curve it was tried to predict the 'dermal bioavailability' in the acceptor (AUCa).

Drug penetration as studied by noninvasive methods: fourier transform infrared-attenuated total reflection, fourier transform infrared, and ultraviolet photoacoustic spectroscopy.

The penetration of the drugs dithranol and methoxsalen from semisolid Vaseline formulation into an artificial dodecanol-collodion membrane was followed by three spectroscopic methods; they are, step-scan Fourier transform infrared (FTIR) photoacoustic spectroscopy (PAS) with phase modulation, FTIR-attenuated total reflection (FTIR-ATR), and ultraviolet (UV) PAS. The uptake of the drug in the membrane was quantified by monitoring the dependence of an appropriate drug band on the penetration time. The PAS experiments were carried out with various modulation frequencies for generating various sampling depths. Based on Fick's second law, the diffusion coefficient was derived by numerical fitting of the experimental data. It appears that the diffusion coefficient for the drug in the membrane depends on the distance. The comparative studies demonstrate that FTIR-ATR is favored for permeation studies, whereas the PAS techniques are capable of providing the drug penetration profile in the membrane. Thus, extended experimental data are available for new insight into the penetration process. However, because of the photacoustic cells at hand, PAS is only suitable for in vitro studies.

Penetration studies of clotrimazole from semisolid formulation using step-scan FT-IR photoacoustic spectroscopy.

PURPOSE: The aim of this study was to elucidate the potential use of the step-scan FT-IR photoacoustic spectroscopy (PAS) for the non-destructive determination of drug penetration into membranes. METHODS: The penetration of clotrimazole from a 10% (w/w) suspension in Vaseline into a dodecanol-collodion acceptor membrane was studied by three methods: the step-scan FT-IR PAS with a phase modulation, a multilayer membrane system, and a modified libration model. Based on Fick's second law, the diffusion coefficient of the drug in the membrane was derived by numerical fitting of the experimental data. RESULTS: The three methods applied provided almost the same diffusion coefficient D = 2.2 10(-9) cm2/s for clotrimazole in the membrane. Because of the non-destructive mode of operation, the accuracy of results obtained by FT-IR PAS is much better than that attainable by other two methods. CONCLUSIONS: Step-scan FT-IR photoacoustic spectroscopy in conjunction with a phase modulation is useful to determine the penetration of drug through membranes. The fact that samples can be investigated without elaborate preparation is an advantage of this spectroscopic technique.