Effect of application volume of ethanol-isopropyl myristate mixed solvent system on permeation of zidovudine and probenecid through rat skin

Permeation of zidovudine (AZT) and probenecid from an ethanol-isopropyl myristate (IPM) mixed system through rat skin was studied in a finite system. Several volume sizes of the ethanol-IPM mixed systems containing AZT and probenecid, both as suspensions, were applied on the skin of the hairless rat using a vertical glass cell, and the fractions of the drugs permeated in 8 hr Q_%,8hr were determined. For the systems containing 40% ethanol, the Q_%,8hr value decreased with the reduction of volume of the system applied, and the decreasing profile was similar to that calculated on the assumption that the permeability of the drug does not change with the volume of the sample applied. On the other hand, in the systems containing 10% or 20% ethanol, the Q_%,8hr value showed a maximum when a specific volume of the sample was applied. Therefore, the effect of sample volume on the Q_%,8hr value was different between the 40% ethanol-IPM system and the 10% or 20% ethanol-IPM system. Following pretreatment of the skin with 0.105 ml/cm² of drug-free 40% ethanol-IPM for 2 hr, several volume sizes of 10% ethanol-IPM systems containing the drugs were applied on the skin to explain why the different profiles were observed in the system containing 10% or 20% ethanol. The results for pretreated skin suggest that the amount of ethanol in the systems with low ethanol concentration and small application volume is too small to exert an effect that enhances permeation of the drugs. In those systems, the integrated effect of ethanol on the skin would be important for the enhancing effect. Total volume, as well as concentration, of an enhancer should be set precisely in designing an efficient transdermal delivery system.     

Transdermal Absorption of Zidovudine from Ethanol-Isopropyl Myristate Mixed System and Influence of Probenecid on It in Rats

Abstract

Transdermal absorption of zidovudine (AZT) from an ethanol-isopropyl myristate (IPM) mixed system was examined in rats. For comparison of bioavailability (BA) after topical applications, 0.25 ml of the ethanol/IPM system containing 40% ethanol and 60 mM AZT was applied as a standard formulation. Values of the area under the plasma concentration-time curves of AZT for 8 hr (AUC_0-8), as indices of BA, following application of various formulations were compared with that of the standard formulation. Then the influence of content of the drug and ethanol, and application volume of the system was evaluated. BA was effectively improved only when the total amount of ethanol applied on the skin was increased. On the other hand, simultaneous transdermal application of AZT and probenecid increased the AU_0-8, of AZT without necessitating the increase in ethanol content in the formulation. In addition, coadministered probenecid improved cerebrospinal fluid/plasma concentration ratio of AZT.     

Transdermal Absorption of Zidovudine from Ethanol-Isopropyl Myristate Mixed System and Influence of Probenecid on It in Rats

Transdermal absorption of zidovudine (AZT) from an ethanol-isopropyl myristate (IPM) mixed system was examined in rats. For comparison of bioavailability (BA) after topical applications, 0.25 ml of the ethanol/IPM system containing 40% ethanol and 60 mM AZT was applied as a standard formulation. Values of the area under the plasma concentration-time curves of AZT for 8 hr (AUC_0-8), as indices of BA, following application of various formulations were compared with that of the standard formulation. Then the influence of content of the drug and ethanol, and application volume of the system was evaluated. BA was effectively improved only when the total amount of ethanol applied on the skin was increased. On the other hand, simultaneous transdermal application of AZT and probenecid increased the AU_0-8, of AZT without necessitating the increase in ethanol content in the formulation. In addition, coadministered probenecid improved cerebrospinal fluid/plasma concentration ratio of AZT.     

Permeation of Zidovudine and Probenecid from Oily Bases Containing Alcohols Through Rat Skin

Permeation of zidovudine (3'-azido-3'-deoxythymidine, AZT) and probenecid from oily bases containing an alcohol through rat skin was examined. Isopropyl myristate (IPM), as an oily vehicle, showed a penetration enhancing effect for AZT and probenecid. Ethanol, n-propanol, and n-butanol were used as additives in IPM and were examined for their own permeation and the enhancing effect on the permeation of AZT and probenecid. The skin permeation of AZT and probenecid from IPM was enhanced by addition of the alcohol in IPM. The degree of the enhancement was decreased with increasing lipophilicity of the alcohol used. me permeation rate of the drug from those systems was shown to be governed by penetration-enhancing effects of the oily base and alcohol, and the penetration of the alcohol itself through the skin.     

Comparison of Skin Permeation of Dideoxynucleoside-Type Anti-HIV Drugs: Alone Versus Combination

The effects of vehicles and skin permeation enhancer on the skin permeation of dideoxynucleoside-type anti-HN drugs, Zalcitabine (DDC), Didanosine (DDI), and Zidovudine (AZT), alone and in combination, were compared using hairless rat and human cadaver skins. Each drug alone or a combination of three drugs was added to various compositions of ethanol/water or ethanol/tricaprylin cosolvent system to saturation, and in vitro skin permeation studies were conducted using Valia-Chien skin permeation cells. In both ethanol/water and ethanol/tricaprylin systems, the hairless rat skin permeation rates achieved by each drug alone and three drugs in combination were not significantly different. Addition of oleic acid [1.0% (v/v) for each drug alone and 5.0% (v/v) for drug combination] in ethanol/tricaprylin (50:50) could not significantly enhance the skin permeation of these drugs. In hairless rat skin permeation of each drug alone, the permeation rates of all three drugs were dramatically enhanced with the addition of oleic acid in ethanol/water (60:40) cosolvent system and reached plateau level with oleic acid as low as 0.3% (v/v). However, in the case of drug combination, the enhancement of skin permeation rates of these drugs with the addition of oleic acid in ethanol/water (80:20) cosolvent system was not as high as that observed for each drug alone, and plateau level was not observed even at 5.0% (v/v) of oleic acid. Human cadaver skin permeation rates of each drug alone saturated in ethanol/ water (60:40) cosolvent system containing 1.0% (v/v) of oleic acid were 3-4 times lower than those of hairless rat skin. However, in skin permeation of three drugs in combination, saturated in ethanol/water (80:20) cosolvent system containing 5.0% (v/v) of oleic acid, human cadaver skin permeation rates of DDC and DDI were slightly lower than those of hairless rat skin, and there was no significant difference between the two skins for AZT. These results show that mutual skin permeation-enhancing effects of oleic acid and an ethanol/water cosolvent system Made the transdermal delivery of anti-HIV drugs, alone and in combination, feasible.     

Comparison of Skin Permeation of Dideoxynucleoside-Type Anti-HIV Drugs: Alone Versus Combination

Abstract

The effects of vehicles and skin permeation enhancer on the skin permeation of dideoxynucleoside-type anti-HN drugs, Zalcitabine (DDC), Didanosine (DDI), and Zidovudine (AZT), alone and in combination, were compared using hairless rat and human cadaver skins. Each drug alone or a combination of three drugs was added to various compositions of ethanol/water or ethanol/tricaprylin cosolvent system to saturation, and in vitro skin permeation studies were conducted using Valia-Chien skin permeation cells. In both ethanol/water and ethanol/tricaprylin systems, the hairless rat skin permeation rates achieved by each drug alone and three drugs in combination were not significantly different. Addition of oleic acid [1.0% (v/v) for each drug alone and 5.0% (v/v) for drug combination] in ethanol/tricaprylin (50:50) could not significantly enhance the skin permeation of these drugs. In hairless rat skin permeation of each drug alone, the permeation rates of all three drugs were dramatically enhanced with the addition of oleic acid in ethanol/water (60:40) cosolvent system and reached plateau level with oleic acid as low as 0.3% (v/v). However, in the case of drug combination, the enhancement of skin permeation rates of these drugs with the addition of oleic acid in ethanol/water (80:20) cosolvent system was not as high as that observed for each drug alone, and plateau level was not observed even at 5.0% (v/v) of oleic acid. Human cadaver skin permeation rates of each drug alone saturated in ethanol/ water (60:40) cosolvent system containing 1.0% (v/v) of oleic acid were 3-4 times lower than those of hairless rat skin. However, in skin permeation of three drugs in combination, saturated in ethanol/water (80:20) cosolvent system containing 5.0% (v/v) of oleic acid, human cadaver skin permeation rates of DDC and DDI were slightly lower than those of hairless rat skin, and there was no significant difference between the two skins for AZT. These results show that mutual skin permeation-enhancing effects of oleic acid and an ethanol/water cosolvent system Made the transdermal delivery of anti-HIV drugs, alone and in combination, feasible.     

Topical Oleo-Hydrogel Preparation of Ketoprofen with Enhanced Skin Permeability

In an attempt to improve the skin penetration of ketoprofen, various transdermal formulations were prepared, and their in vitro skin permeability and in vivo percutaneous absorption were evaluated. In vitro permeation studies were performed using a modified Franz cell diffusion system in which permeation parameters such as cumulative amount at 8 hr Q_8hr, steady-state flux J_ss, or lag time t_L were determined. In the in vivo percutaneous absorption study using the hairless mouse, maximum concentration C_max and area under the curve at 24 hr AUC_24h were measured. The optimal transdermal formulation (oleo-hydrogel formulation) of ketoprofen showed a Q_8hr value of 227.20 μg/cm², a J_ss value of 29.61 μg/cm²/hr, and a t_L value of 0.46 hr. The Q_8hr and J_ss values were about 10-fold (p <. 01) higher than those (Q_8hr = 19.61 μg/cm²; J_ss = 2.66 μg/cm²/hr) from the K-gel and about 3.5-fold (p <. 01) than those (Q_8hr = 60.00 μg/cm²; J_ss = 7.99 μg/cm²/hr) of the K-plaster. In the in vivo percutaneous absorption, the C_max (6.82 μg/ml) and AUC_24h (55.74 μg·hr/ml) values of the optimal formulation were significantly (p <. 01) higher than those of K-gel and K-plaster. The relative bioavailability of the oleo-hydrogel following transdermal administration in reference to oral administration was about 37%, and the C_max value (4.73 μg/cm²) in the hypodermis following topical administration was much higher than those from the conventional products (C_max of K-gel and K-plaster were 0.92 ± 0.19 μg/cm² and 1.27 ± 0.37 μg/cm², respectively). These data demonstrate that the oleo-hydrogel formulation of ketoprofen was more beneficial than conventional products (K-gel and K-plaster) in enhancing transdermal permeation and skin absorption of ketoprofen. Furthermore, there was a good correlation between in vitro permeation parameters and in vivo percutaneous absorption parameters.     

Effect of Nerodilol and Carvone on in vitro Permeation of Nicorandil Across Rat Epidermal Membrane

ABSTRACT

The objective of the study was to investigate the effect of nerodilol and carvone on the in vitro transdermal delivery of nicorandil so as to fabricate a membrane-moderated transdermal therapeutic system. The in vitro permeation studies were carried across the rat epidermal membrane from the hydroxypropyl methylcellulose (HPMC) gels (prepared with 70:30 v/v ethanol–water) containing selected concentrations of a terpene such as nerodilol (0% w/w, 4% w/w, 8% w/w, 10% w/w, or 12% w/w) or carvone (0% w/w, 4% w/w, 8% w/w, 12% w/w, or 16% w/w). The amount of nicorandil permeated (Q₂₄) from HPMC gel drug reservoir without a terpene was 3424.6 ± 51.4 μg/cm², and the corresponding flux of the drug was 145.5 ± 2.2 μg/cm²· h. The flux of nicorandil increased with an increase in terpene concentration in HPMC gel. It was increased ranging from 254.9 ± 3.1 to 375.7 ± 3.2 μg/cm²·h or 207.6 ± 4.7 to 356.7 ± 15.3 μg/cm²· h from HPMC gels containing nerodilol (4% w/w to 12% w/w) or carvone (4% w/w to 16% w/w), respectively. Nerodilol increased the flux of nicorandil by about 2.62-folds whereas carvone increased the flux of the drug by about 2.49-folds across the rat epidermal membrane. The results of the Fourier Transform Infrared (FT-IR) study indicated that the enhanced in vitro transdermal delivery of nicorandil might be due to the partial extraction of stratum corneum lipids by nerodilol or carvone. It was concluded that the terpenes, nerodilol and carvone, produced a marked penetration enhancing effect on the transdermal delivery of nicorandil that could be used in the fabrication of membrane-moderated transdermal therapeutic systems.     

Formulation and evaluation of ubidecarenone transdermal delivery systems

Purpose: This study is aimed to examine the feasibility of developing ubidecarenone (coenzyme Q₁₀, CoQ₁₀) transdermal delivery systems (TDS). Method: In vitro permeation study using solution formulation and pressure-sensitive adhesive (PSA) TDS and in vivo pharmacokinetic study were conducted. Results: When using solution formulations, isopropyl alcohol (103.39 ± 1.61), ethyl alcohol (81.55 ± 7.27), and the mixture of diethylene glycol monoethyl ether (DGME)/propylene glycol monolaurate (PGML) at the ratio of 60:40 (91.08 ± 26.07) showed high flux (μg/cm²/hour). The addition of fatty acids to DGME-PGML failed to show profound enhancing effects; only unsaturated fatty acids such as linoleic acid and oleic acid at 3% and caprylic acid at 3% and 10% slightly increased permeation flux. CoQ₁₀ from the acrylic PSA TDS showed biphasic permeation profile that was permeated very rapidly up to the first 12 hours, and after that, permeation rate became slower. Overall, 6% fatty acids showed high permeation rates and the highest maximum flux of 9.3 μg/cm²/hour was obtained with a formulation containing 6% lauric acid in DGME-PGML (60:40). The in vivo pharmacokinetic study using TDS with 6% fatty acids in DGME-PGML (60:40) showed that the absorption of CoQ₁₀ decreased in the following order: TDS containing linoleic acid > oral dosage form > TDS with oleic acid > TDS with lauric acid > TDS with caprylic acid > TDS with capric acid. TDS containing oleic acid showed preferable pharmacokinetic profile with respect to lower C_max, comparable AUC, and prolonged t_1/2 and T_max compared to oral administration of drug. Conclusions: For effective transdermal delivery system of CoQ₁₀, 6% linoleic acid or oleic acid in DGME-PGML (60:40) could be employed.     

Effect of mixing procedures and compaction pressures on the powder reaction of CuO-η-Al2O3 and ZnO-η-Al2O3 systems

The rate of reaction of the compacted powders of CuO-η-Al₂O₃ and ZnO-η-Al₂O₃ systems was measured in air at 800 to 900° C and the effect of the mixing procedure (dry and wet mixing) and compaction pressure (0 to 8.3×10⁸ Pa) of reactant oxides on the fraction of reaction completed (α) was investigated. In the reaction of the CuO-η-Al₂O₃ system, the α-values obtained for the sample prepared by wet mixing in ethanol were higher than those for the sample prepared by dry mixing in air and were not influenced by the compaction pressure, whereas in the case of dry mixing they varied with the compaction pressure and had a maximum value at 2.1×10⁸ Pa. On the other hand, in the reaction of the ZnO-η-Al₂O₃ system the α-values for the sample obtained by wet mixing were lower than the values obtained by dry mixing, in contrast to the results in CuO-η-Al₂O₃ system, and the α-values for the samples prepared by both dry and wet mixing were not influenced by the compaction pressure. The effect of mixing procedure and compaction pressure of reactant powders on the α-values was found to be explained on the basis of the aggregate size of CuO and ZnO dispersed in the matrix of η-Al₂O₃ fine powder.     

Development of hydrophilic gels containing coenzyme Q10-loaded liposomes: characterization,stability and rheology measurements

Objective: The aim of this study was to develop, characterize and evaluate stability of a gel containing coenzyme Q₁₀ (Q₁₀)-loaded liposomes, and enhance the stability of Q₁₀ in the nanocarrier-containing gel compared to the conventional gel.

Methods: Q₁₀-loaded liposome dispersions prepared from unsaturated or saturated lecithin, were characterized for particle size, polydispersity index (PDI), zeta-potential, pH value, oxidation index, Q₁₀-content and morphology, and incorporated into carbomer gel. Liposome gels and liposome-free gel were analyzed for flow properties, pH values, Q₁₀-content, and liposomes size and PDI (liposome gels), 48?h after preparation and in predetermined time intervals during 6?months storage at different temperatures in order to predict their long term stability.

Results: Liposomes were of small particle size, homogeneous, negatively charged, and their incorporation into gel did not significantly change (p?>?.05) their particle size and PDI. All gels revealed non-Newtonian, shear-thinning plastic flow behavior during storage with no marked changes in rheological parameters. Storage of gels did not significantly influence the pH value (p?>?.05), while it significantly decreased Q₁₀-content (p?<?.05). Q₁₀ was significantly more (p?<?.05) stable in liposome gel containing unsaturated lecithin liposomes (G1) than in gel containing saturated lecithin liposomes (G2) and liposome-free gel (G3).

Conclusions: Q₁₀-loaded liposome gel G1 was the optimal formulation, since during storage at different temperatures, it did not show significant increase in liposome size and PDI, it provided significantly higher stability for Q₁₀ than other gels and its pH value was suitable for skin application. Due to limited Q₁₀-stability it should be stored at 4?°C.     

The Enhanced Iontophoretic Transport of TRH and Its Impedance Study

Abstract

The transdermal drug delivery of iontophoresis provides a noninvasive method for the administration of effective drugs. The enhanced iontophoretic transport of thyrotropin-releasing hormone (TRH), a tripeptide with molecular weight of 362 and a pK_a of 6.2, through an excised rabbit skin has been achieved by in vitro iontophoresis. The results indicate that the steady-state flux of TRH in a diffusion cell is proportional to the current density. In addition, the electrochemical properties of rabbit skin were studied with impedance spectroscopy, and it was found that the skin impedance decreased to a low and stable value with respect to its initial skin impedance while a current was applied through the rabbit skin. This is in good agreement with our experimental results on iontophoretic transport. As compared to passive diffusion, the iontophoresis dramatically increased the transport fluxes of TRH, and ethanol pretreatment further enhanced its iontophoretic transport. A practical implication of these results is that iontophoresis with a chemical permeation enhancer (ethanol pretreatment) can be applied to enhance and control the transdermal delivery of peptides.     

Effect of solvent and cosolvent on friction welding properties between part of PMMA with PVC

The effect of distilled water, methanol, ethanol, acetone and cosolvent (comprising ethanol and distilled water, the volume fraction of ethanol in the cosolvent was 10V_f% and 20V_f%) on the friction welding properties between parts of PMMA with PVC is investigated. Treatment with those solvents, 20V_f% cosolvent and 10V_f% cosolvent promote about 360%, 280% and 110% more bonding strength than without any solvent treatment. The tensile fracture morphology of welded PMMA with PVC has three zones: the non-plasticized central zone (Fud), the plasticized peripheral zone (Fpl), and the partly plasticized zone between Fud and Fpl (Fpd). Comparing tensile fracture morphology and residual solvent with bonding strength, it has larger Fpd regions, no Fud in the central part and less residual solvent is responsible for better bonding strength.     

Visualization Recording and Storage of Pressure Distribution through a Smart Matrix Based on the Piezotronic Effect

Pressure sensors that can both directly visualize and record applied pressure/stress are essential for e‐skin and medical/health monitoring. Here, using a WO₃‐film electrochromic device (ECD) array (10 × 10 pixels) and a ZnO‐nanowire‐matrix pressure sensor (ZPS), a pressure visualization and recording (PVR) system with a spatial resolution of 500 µm is developed. The distribution of external pressures can be recorded through the piezotronic effect from the ZPS and directly expressed by color changes in the ECD. Applying a local pressure can generate piezoelectric polarization charges at the two ends of the ZnO nanowires, which leads to the tuning of the current to be transported through the system and thus the color of the WO₃ film. The coloration and bleaching process in the ECD component show good cyclic stability, and over 85% of the color contrast is maintained after 300 cycles. In this PVR system, the applied pressure can be recorded without the assistance of a computer because of the color memory effect of the WO₃ material. Such systems are promising for applications in human‐electronic interfaces, military applications, and smart robots.     

Effects of metakaolin on autogenous shrinkage of cement pastes

The effects of partial replacements (5%, 10%, 15% and 20%) of Portland cement by high-purity metakaolin (MK) on the autogenous shrinkage of pastes (water/binder ratios 0.3 and 0.5) were investigated. In order to distinguish the effect of heterogeneous nucleation and pozzolanic activity from the dilution effect, some mixes were prepared using a coarse powder (Q_ref) instead of MK (10% and 20% for both w/b ratios). The hydration of cement–MK pastes was followed qualitatively by differential thermal analysis (DTA). DTA showed that C–S–H and gehlenite (C₂ASH₈) were the main compounds produced by MK pozzolanic reaction. Results showed that the long-term autogenous shrinkage of cement–MK pastes, for both w/b ratios, decreased as the cement replacement level by MK increased. No expansion was observed at early ages, contrary to the findings of other authors. With the elimination of the dilution effect, it was shown, at early ages, that the increase of autogenous shrinkage of the cement–MK pastes relative to cement–Q_ref mixes was due to heterogeneous nucleation. At later ages, autogenous shrinkage became lower for cement–MK pastes than for cement–Q_ref pastes, surely because the pozzolanic activity of MK became predominant. This behavior i.e. reduction of autogenous shrinkage, is one more benefit confirming the interest of using MK in concrete.     

Search for Enhancement of the Isobaric Thermal Expansion Coefficient of Superfluid 4He near T �� by?a?Heat Current

We report an experimental search for the enhancement of the isobaric thermal expansion coefficient (?? _P ) of superfluid ⁴He near the superfluid transition by a heat current (Q). The experiment was carried out using the hot volume technique at constant sample pressure of 1 bar. Liquid helium was contained in a thermal conductivity cell, and a constant heat current, Q=10 or 100 ??W/cm², was supplied from below through the sample column. We performed a sample density calculation based on existing helium properties known in the literature and a proposed enhancement ???? _P (Q). Both calculations, with or without the ?? _P enhancement, agree qualitatively with the measurement. The lack of definitive differentiation indicates that the ?? _P enhancement cannot be definitively resolved by our measurement in spite of applications of high-resolution thermometry and pressure regulation.     

A study on the dust control effect of the dust extraction system in TBM construction tunnels based on CFD computer simulation technology

In order to control dust in a tunnel boring machine (TBM) construction tunnels, this paper, in combination with field measurements, applies CFD computer simulation technology to study the dust control effect of TBM construction tunnels under different dust extraction flow rates. Firstly, the dust extraction system is closed, and the result of the simulation show that the dust diffuses to the entire TBM working area within 181 s, indicating the necessity of having a dust extraction system in the tunnel. Secondly, the dust extraction system is open and under the original dust extraction flow rate of Q_e = 8 m³/s, the overall dust diffuses to the entire working area L_o = 130 m, and the full-face dust diffusion distance is L_f = 47.54 m. Then the study was carried out with the setting of 2 m³/s ≤ Q_e ≤ 14 m³/s. The results show that: when Q_e ≤ 8 m³/s, the full-face dust diffuses to 47.54–71.84 m; when Q_e > 8 m³/s, the full-face dust can be controlled at 42.81–46.34 m; and when Q_e = 8 m³/s, the full-face dust control effect is better, and the average dust concentration in the tunnel is as low as 12.25 mg/m³, indicating that the original dust extraction system has a better design. The field measurement results verify that the CFD computer simulation results are accurate.     

Effect of zirconia addition on crystallinity,hardness, and microstructure of gel-derived barium aluminosilicate,BaAl2Si2O8

The effect of zirconia (ZrO₂) additions, in amounts equivalent to 5, 10, 20 and 40 mol%, to barium aluminosilicate, BaAl₂Si₂O₈, was studied by examination of the phase assemblage of the mixtures after crystallization heat treatments at ∼ 1050°C or more using X-ray diffraction (XRD). In all cases, BaAl₂Si₂O₈ gel crystallized into the hexacelsian polymorph. XRD results also indicated solid solubility of 10mol% or more ZrO₂ in hexacelsian material. Precipitation of an additional phase, tetragonal ZrO₂, occurred in the BaAl₂Si₂O₈ material containing 20 mol% ZrO₂. Also, 95% and 99% dense celsian ceramics were fabricated at 1450 and 1580°C sintering temperatures, respectively, using cold isostatically pressed pellets produced from powder mixtures containing 20 and 40 mol% ZrO₂. These pellets also contained 20 wt% gel-derived lithia-doped celsian “seed” powder to promote hexacelsian to celsian transformation during sintering. Indentation hardness values for the 99% dense celsian ceramic without and with 20 mol% ZrO₂ were 8.04 and 10.80 GPa, respectively. Scanning electron microscopy was used to examine the microstructures of these samples.     

Accurate Measurements of Surface Resistance of HTS Films Using a Novel Transmission Mode Q-Factor Technique

Microwave characterization of HTS films, using typically a sapphire dielectric resonator can only be as accurate as the Q₀-factor and f_res measurements. A novel Transmission Mode Q-Factor (TMQF) technique has been used for accurate measurements of surface resistance of YBa₂Cu₃O₇ films, with errors lower than 1%. The method allows for accurate determination of Q_L, ₁, and ₂ based on novel equations and a multi-frequency circle-fitting technique applied to S₂₁, S₁₁, and S₂₂ measured around the resonance. Parasitic effects introduced by real measurement systems, namely, noise, crosstalk, coupling loss, coupling reactance, and electrical delay due to uncalibrated transmission lines are compensated for in the new method. Range of unloaded Q₀-factors that can be measured with the TMQF technique is assessed to be from 100 to 10 million at the GHz range of frequencies.     

In vitro–in vivo correlation study for the dermatopharmacokinetics of terbinafine hydrochloride topical cream

Background: To investigate the relationship between dermatopharmacokinetic (DPK) tape stripping from in vitro and in vivo using 1% terbinafine hydrochloride topical cream as the model formulation.

Methodology: In vitro and in vivo tape strippings were conducted on separated pig ear skin used as a biological membrane for franz diffusion cell testing and the non-hairy skin area at the ventral forearms of healthy volunteers, respectively. Terbinafine (1%) topical cream was applied to the skin for 0.5, 2, and 4?h. The drug profiles of terbinafine across the stratum corneum were determined immediately (time 0?h), and at 0.5, 1, 2, and 4?h after removing the formulation. The amounts of terbinafine were analyzed by a validated high-performance liquid chromatography-ultraviolet method. The area under the curve (AUC) and the maximum amounts of terbinafine absorption (Q_max) were obtained from pharmacokinetic software. Partition coefficient (K_SC/veh) and diffusion parameter (D/L²) were derived from the Fick’s second law equation. During the schedule time of 8?h, the deviations of in vitro and in vivo data were 6.61 and 30.46% for AUC and Q_max, respectively. There was insignificant difference of the K_SC/veh and the D/L² between excised pig ear and human skin. In addition, K_SC/veh and D/L² at T_max of 2?h were used to predict the AUC presented the value of 4.7481 %h whereas the true value calculated from pharmacokinetic software provided the value of 5.9311 %h differing from each other in approximate of 20%.

Conclusions: In vitro tape stripping using the separated pig ear skin as a viable membrane of the franz diffusion cell testing demonstrates the potential to represent in vivo tape stripping in human for topical bioavailability/bioequivalence study of terbinafine hydrochloride 1% topical cream.