Influence of pH on the permeability of p-toluidine and aminopyrine through shed snake skin as a model membrane

The influence of pH on the permeability of p-toluidine (pKa, 5.3) and aminopyrine (pKa, 5.0) through shed snake skin as a model membrane was studied. The pH was adjusted to several values, and the solubility of the drugs in each donor was measured. Flux rates and permeability coefficients were calculated from the steady-state penetration portions. The flux rates of p-toluidine decreased as the pH value in the donor solution increased. On the other hand, the flux rates of aminopyrine were constant at any pH value. The permeability coefficients of each drug increased as the pH value in the donor solution increased. The partition coefficients (octanol/buffer) of each drug were dependent on the molecular fraction of un-ionized species. From these results, it is suggested that ionized species of p-toluidine transports through shed snake skin, but the ionized species of aminopyrine does not.     

Influence of pH on the Permeability of p-Toluidine and Aminopyrine Through Shed Snake Skin as a Model Membrane

The influence of pH on the permeability of p-toluidine (pKa, 5.3) and aminopyrine (pKa, 5.0) through shed snake skin as a model membrane was studied. The pH was adjusted to several values, and the solubility of the drugs in each donor was measured. Flux rates and permeability coefficients were calculated from the steady-state penetration portions. The flux rates of p-toluidine decreased as the pH value in the donor solution increased. On the other hand, the flux rates of aminopyrine were constant at any pH value. The permeability coefficients of each drug increased as the pH value in the donor solution increased. The partition coefficients (octanol/buffer) of each drug were dependent on the molecular fraction of un-ionized species. From these results, it is suggested that ionized species of p-toluidine transports through shed snake skin, but the ionized species of aminopyrine does not.     

In vitro studies on transdermal permeation of butorphanol

The influence of the donor vehicles pH and the addition of laurocapram or transkarbam 12 as permeation enhancers on the transdermal permeation of butorphanol through human skin were examined with the aim of finding out about its possible use in the transdermal delivery system. As the pH of the donor vehicles rises, the mean value of butorphanol skin fluxes declines; an exponential relationship of the means of butorphanol flux values against the pH of the buffered aqueous donor vehicles has been demonstrated. The presence of 1% of transkarbam 12 (T12) or 5% of laurocapram (LC), respectively, in an isopropylmyristate (IPM) donor vehicle increased transdermal fluxes of butorphanol almost 2.5 times (58.1 ± 5.7 μg cm^-2 hr^-1) or 1.5 times (36.4 ± 7.0 μg cm^-2 hr^-1), respectively, when compared to blank donors. Considering clinical and pharmacokinetic data on butorphanol, it is possible to expect that a transdermal preparation sized 20 cm² and possessing flux values ranging between 5.1 and 15.3 μg cm^-2 hr^-1 should be sufficient to achieve effective butorphanol transdermal fluxes, namely using IPM donors containing T12. In conclusion, butorphanol is a suitable candidate for transdermal administration and T12 is a very a suitable enhancer for it.     

In-vitro transdermal permeation of oxycodone: (I) effect of PH, delipidization and skin stripping

The effect of pH, skin stripping and delipidization on the in-vitro transdermal permeation of a weak base analgesic, oxycodone (pKa=8.53), was studied using hydrodynamically calibrated Valia-Chien diffusion cells. Saturated oxycodone. HCl solutions in citrate-phosphate buffers ranging from pH 4 to 10 were used as the donor solution. Skin samples from the abdominal and dorsal sites of hairless rats, abdominal site of hairless mouse, rabbit pinna ear, as well as human cadaver skin were used in permeation studies. The pHs at which maximum flux attained varied from 6.5 to 7.5 depending upon animal model. The permeabilities of protonated form through intact skin of all the animal models used, was about 7-15 fold lower than that of nonionic form. The unexpected high permeation rate at pHs ranges 4 to 6.5 across human cadaver could be attributed to the possible damage upon storage. The skin stripping and delipidizaton process appeared to increase the permeation rates of oxycodone and the degree enhancement is dependent upon the pH in the donor compartment.     

In-vitro transdermal permeation of oxycodone: (I) effect of PH,delipidization and skin stripping

Abstract

The effect of pH, skin stripping and delipidization on the in-vitro transdermal permeation of a weak base analgesic, oxycodone (pKa=8.53), was studied using hydrodynamically calibrated Valia-Chien diffusion cells. Saturated oxycodone. HCl solutions in citrate-phosphate buffers ranging from pH 4 to 10 were used as the donor solution. Skin samples from the abdominal and dorsal sites of hairless rats, abdominal site of hairless mouse, rabbit pinna ear, as well as human cadaver skin were used in permeation studies. The pHs at which maximum flux attained varied from 6.5 to 7.5 depending upon animal model. The permeabilities of protonated form through intact skin of all the animal models used, was about 7-15 fold lower than that of nonionic form. The unexpected high permeation rate at pHs ranges 4 to 6.5 across human cadaver could be attributed to the possible damage upon storage. The skin stripping and delipidizaton process appeared to increase the permeation rates of oxycodone and the degree enhancement is dependent upon the pH in the donor compartment.     

Characterization of Transdermal Delivery of Nefopam Hydrochloride under Iontophoresis

In vitro iontophoretic delivery of nefopam hydrochloride was conducted to study the effects initial drug concentration, pH, ionic strength and viscosity of the donor solutions on the transdermal flux through a hairless mouse skin. Stability of nefopam hydrochloride under the experimental conditions was investigated. Type of electrode, current intensity, electric voltage and electrode distance were evaluated. Appropriate conditions were selected to minimize the potential degradation problems of nefopam hydrochloride during iontophoresis. Results show that the silver/silver chloride electrode provides better drug stability than the platinum electrode. Higher current intensity resulted in faster transdermal flux and therefore better drug permeability. The increase in the drug permeability appears to be proportionally increased as the current intensity increases in the range of 0.253 to 1.265 mA/cm². The iontophoretic transdermal delivery of nefopam hydrochloride was observed to increase as the drug concentration in the donor site was increased until it's close to the equilibrium concentration. The optimum pH to achieve the best iontophoresis under constant current was determined to be at pH 3.0. This may be due to the highest available charge density of nefopam was achieved at this pH to provide the best conductance. A decrease in the iontophoretic transdermal flux was encountered as an increase in the solution ionic strength due to the increased competition of similar charged ions with the available current. The increase in the donor solution viscosity decreased the conductivity of the ions and hindered the trandermal flux of the drug under iontophoresis.     

Characterization of Transdermal Delivery of Nefopam Hydrochloride under Iontophoresis

In vitro iontophoretic delivery of nefopam hydrochloride was conducted to study the effects initial drug concentration, pH, ionic strength and viscosity of the donor solutions on the transdermal flux through a hairless mouse skin. Stability of nefopam hydrochloride under the experimental conditions was investigated. Type of electrode, current intensity, electric voltage and electrode distance were evaluated. Appropriate conditions were selected to minimize the potential degradation problems of nefopam hydrochloride during iontophoresis. Results show that the silver/silver chloride electrode provides better drug stability than the platinum electrode. Higher current intensity resulted in faster transdermal flux and therefore better drug permeability. The increase in the drug permeability appears to be proportionally increased as the current intensity increases in the range of 0.253 to 1.265 mA/cm². The iontophoretic transdermal delivery of nefopam hydrochloride was observed to increase as the drug concentration in the donor site was increased until it's close to the equilibrium concentration. The optimum pH to achieve the best iontophoresis under constant current was determined to be at pH 3.0. This may be due to the highest available charge density of nefopam was achieved at this pH to provide the best conductance. A decrease in the iontophoretic transdermal flux was encountered as an increase in the solution ionic strength due to the increased competition of similar charged ions with the available current. The increase in the donor solution viscosity decreased the conductivity of the ions and hindered the trandermal flux of the drug under iontophoresis.     

Liquid-phase microextraction as an on-line preconcentration method in capillary electrophoresis

A simple and efficient sample preconcentration method for capillary electrophoresis has been developed using liquid-phase microextraction (LPME). A thin layer of an organic liquid was used to separate a drop of the aqueous acceptor phase hanging at the inlet of a capillary from the bulk aqueous donor phase. The donor-phase pH was 1.0, and the acceptor phase pH was 9.5. This pH difference caused the preconcentration of the acidic compounds, fluorescein and fluorescein isothiocyanate, into the acceptor-phase drop. Enrichment factors of 3 orders of magnitude were obtained with 30-min LPME at 35 degrees C.     

Peptide washout and permeability from glyceryl monooleate buccal delivery systems

Simultaneous evaluation of the permeation and washout of a peptide from the mucoadhesive liquid crystalline phases of glyceryl monooleate (GMO) has been investigated using a donor compartment flow-through diffusion cell. [D-Ala2, D-Leu5]enkephalin (DADLE) was incorporated into the cubic and lamellar liquid crystalline phases of GMO and applied to excised porcine buccal mucosa mounted in the donor compartment flow-through cell. Phosphate-buffered saline pH 7.4 (PBS) was pumped across the upper surface of the liquid crystalline phases to mimic salivary flow. The steady-state fluxes of DADLE and GMO from the cubic phase were significantly greater than that from the lamellar phase (P < 0.01). There was no statistical difference between the amounts of DADLE and GMO washed out from the lamellar and cubic phases (P > 0.05). The donor compartment flow-through diffusion cell was found to be a useful tool to evaluate the impact of salivary washout on mucoadhesive oral mucosal delivery systems.     

Effect of pH on surface energy of glass and Teflon and theoretical prediction of Staphylococcus aureus adhesion

The surface energy of glass and Teflon at various pH values was examined. Contact angle was used to determine physico-chemical substratum properties. The surface energy of both substratums including, hydrophobicity, and electron donor/electron acceptor (Lewis acid–base properties) were found to depend on pH of contact solution. The maximum of hydrophobicity (higher negative value of ΔG_iwi) was obtained at pH 11 and pH 6.5 for glass and Teflon respectively. The electron donor property was higher at pH 5 and pH 3 for glass and Teflon respectively. Moreover, prediction of Staphylococcus aureus adhesion on both substratums was estimated by calculating the total interaction free energy (ΔG^Tot). Based on the value of ΔG^Tot, S. aureus should adhere to glass at pH 2, pH 3 and pH 11 with the maximal adhesion obtained at pH 3 and pH 11. For Teflon, regardless of pH values, S. aureus should be able to attach on this substratum with the high adhesion level at pH 5. The relation between surface energy of substratum and the total interaction free energy was also examined. Based on this relation and the value of the components of total interaction free energy, we show that adhesion to glass could be governed by both short range forces (Lewis acid–bases forces) and by long range forces (van der Waals forces) and the adhesion to Teflon could be mediated only by the short range forces.     

Circular Dichroic Study of the Interaction of Gelatin with Palladium(n)

The structure of the gelatin-palladium(u) complexes formed under a variety of conditions was studied by measuring CD and absorption spectra and comparing them with those of simple peptide complexes. The complex is considered to be tetragonal and tetracoordinate. In the acid pH region the formation of two types of complexes in which palladium(n) is bound by the carboxylate group is proposed, depending on the pH and gelatin concentration. The formation of complexes in which palladium(n) is bound by each of the imidazole and amino groups is shown above around pH 4.5. In the alkaline pH region all of the carboxyl, imidazole and amino groups are involved in complexing, and palladium(u) is presumably coordinated by three peptide nitrogen donor atoms in addition to the ionizable side-group. In both acid and alkaline pH regions an additional band is observed near 260 nm in the circular dichroism spectrum, which is ascribed to the complex with one imidazole nitrogen and three peptide nitrogen donor atoms.     

Sintering and properties of highly donor-doped barium titanate ceramics

The electrical properties of donor (La³⁺) doped BaTiO₃ samples with a donor concentration in the range from 0.3 to 1.5 mol.% of La were studied. Samples were sintered at a low partial pressure of oxygen in order to facilitate anomalous grain growth and donor incorporation. In order to optimise the PTCR anomaly, the samples were annealed in air at 1100°C. Results show that with the use of a specific sintering profile PTCR ceramics containing an amount of donor dopant >0.3 mol.%, can be prepared. Heavily doped samples which do not exhibit anomalous grain growth show a core shell structure.     

The effect of various reaction parameters on bioremediation of perchlorate-contaminated water

The bioremediation was employed to treat perchlorate-contaminated water. All enrichments and growth of mixed cultures were performed in anaerobic acetate medium. Enrichment cultures were started with activated sludge obtained from a local wastewater treatment plant where it predominantly treats domestic wastewater. Several parameters affecting perchlorate removal were examined through batch experiments, these include the amount of domesticated sludge, the acetate concentration, pH, the C/N ratio and the reaction temperature. The results indicated that acetate was an effective carbon source and electron donor. Under the selected conditions, namely 1.0 g domesticated sludge, an acetate concentration of 1.2 g l(-1), pH 8.0, a C/N ratio of 20 at 40 degrees C, 50 mg l(-1) perchlorate could be rapidly reduced to non-detectable levels within 24 h.     

Permeation studies on freshly excised rat gastric mucosa: influence of pH

The objective of this study was to evaluate the influence of pH on the permeation of model drugs through freshly excised rat stomach. Additionally, the capability of excised gastric mucosa to maintain an acidic pH was assessed. In vitro permeation studies were performed in Ussing-type diffusion chambers with rat stomach using fluorescence-labeled bacitracin (bac-FITC), sodium fluorescein (NaFlu), propranolol HCl, and cimetidine as model drugs. The pH was adjusted to pH 1, 2, and 6.8 in the donor chamber and pH 7.4 in the acceptor chamber. The study demonstrated that both, the fore stomach and the glandular gastric mucosa, are capable of maintaining an acidic pH of 1-1.2 in the donor chamber. P(app) (permeation coefficients) were found to be 1.4?±?0.6 ×·10(-7) and 7.6?±?0.7 ×·10(-7) for bac-FITC and 3.3?±?1.5 ×·10(-7) and 2.4?±?0.6 ×·10(-6) cm/sec for NaFlu at pH 2 and 6.8, respectively, in the glandular stomach. In order to evaluate the effect of pH on the integrity of paracellular space, propranolol as high-permeability drug and cimetidine as low-permeability drug were chosen. The P(app) of propranolol HCl was determined to be 5.9?±?0.3 ×·10(-7) and 1.1?±?0.7 ×·10(-6) cm/sec at pH 2 and 6.8, respectively, in the glandular stomach. Cimetidine showed a permeability of 1.4?±?0.4 ×·10(-5) and 9.6?±?2.3 ×·10(-6) cm/sec at pH 2 and 6.8. Results provide essential basic information for the development of gastric drug delivery systems.     

Polymersome-loaded capsules for controlled release of DNA

The formation of a novel drug-delivery carrier for the controlled release of plasmid DNA that comprises layer-by-layer polymer capsules subcompartmentalized with pH-sensitive nanometer-sized polymersomes is reported. The amphiphilic diblock copolymer poly(oligoethylene glycol methacrylate)-block-poly(2-(diisopropylamino)ethyl methacrylate) forms polymersomes at physiological pH, but transitions to unimeric polymer chains upon acidification to cellular endocytic pH. These polymersomes can thus release an encapsulated payload in response to a change in pH from physiological to endocytic conditions. Multicomponent layer-by-layer capsules are formed by exploiting the ability of tannic acid to act as an efficient hydrogen-bond donor for both the polymersomes and poly(N-vinyl pyrrolidone) at physiological pH. These capsules show release of a plasmid DNA payload encapsulated within the polymersome subcompartments in response to changes in pH between physiological and endocytic conditions.     

Nitric oxide-releasing xerogel-based fiber-optic pH sensors

A xerogel-based optical pH sensor capable of releasing low levels of nitric oxide (NO) and measuring changes in solution pH is reported. Through simple dip-coating procedures, aminoalkoxysilane-based xerogel films modified with N-diazeniumdiolate NO donor precursors and the fluorescent pH indicator seminaphthorhodamine-1 carboxylate (SNARF-1) were sequentially deposited onto optical fibers. The resulting sensors were characterized by fast and linear response to pH throughout the physiological range (pH 7.0-7.8). Real-time chemiluminescence measurements confirmed that the presence of the overlying SNARF-1-containing TMOS layer did not have an inhibitory effect on N-diazeniumdiolate formation or NO release, and the NO-releasing coatings were capable of maintaining NO fluxes >0.4 pmol/cm(2) s up to 16 h. In vitro blood compatibility studies using porcine platelets confirmed the expected thromboresistivity of the NO-releasing xerogel coatings.     

Liquid-liquid-liquid microextraction for sample preparation of biological fluids prior to capillary electrophoresis.

Methamphetamine as a model compound was extracted from 2.5-mL aqueous samples adjusted to pH 13 (donor solution) through a thin phase of 1-octanol inside the pores of a polypropylene hollow fiber and finally into a 25-microL acidic acceptor solution inside the hollow fiber. Following this liquid-liquid-liquid microextraction (LLLME), the acceptor solutions were analyzed by capillary zone electrophoresis (CE). Extractions were performed in simple disposable devices each consisting of a conventional 4-mL sample vial, two needles for introduction and collection of the acceptor solution, and a 8-cm piece of a porous polypropylene hollow fiber. From 5 to 20 different samples were extracted in parallel for 45 min, providing a high sample capacity. Methamphetamine was preconcentrated by a factor of 75 from aqueous standard solutions, human urine, and human plasma utilizing 10(-1) M HCl as the acceptor phase and 10(-1) M NaOH in the donor solution. In addition to preconcentration, LLLME also served as a technique for sample cleanup since large molecules, acidic compounds, and neutral components were not extracted into the acceptor phase. Utilizing diphenhydramine hydrochloride as internal standard, repetitive extractions varied less than 5.2% RSD (n = 6), while the calibration curve for methamphetamine was linear within the range 20 ng/microL to 10 micrograms/mL (r = 0.9983). The detection limit of methamphetamine utilizing LLLME/CE was 5 ng/mL (S/N = 3) in both human urine and plasma.     

Degradation of pentachlorophenol in contaminated soil suspensions by potassium monopersulfate catalyzed oxidation by a supramolecular complex between tetra(p-sulfophenyl)porphineiron(III) and hydroxypropyl-beta-cyclodextrin

To enhance the catalytic oxidation of pentachlorophenol (PCP) in contaminated soil suspensions using tetra(p-sulfophenyl)porphineiron(III) (Fe(III)-TPPS) as a catalyst and potassium monopersulfate (KHSO(5)) as the single-oxygen donor, the effect of added hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was examined. At pH 4 and 6, the percentage of PCP disappearance increased substantially in the presence of HP-beta-CD. In addition, the self-degradation of Fe(III)-TPPS was significantly retarded in the presence of HP-beta-CD. This retarded self-degradation can be attributed to the stabilization of Fe(III)-TPPS via the formation of a supramolecular complex with HP-beta-CD. The kinetic constant for the self-degradation of Fe(III)-TPPS in the presence of HP-beta-CD at pH 6 was much smaller than that at pH 4, indicating that Fe(III)-TPPS is more stable at pH 6. Thus, the amount of Fe(III)-TPPS, KHSO(5) and HP-beta-CD required to degrade PCP in contaminated soil suspensions was optimal at pH 6. When PCP-contaminated soil suspensions were treated under the optimized conditions, 12-18% and 24-28% of the PCP was mineralized to CO(2) in the absence and presence of HP-beta-CD, respectively. These results show that the presence of HP-beta-CD in the Fe(III)-TPPS/KHSO(5) catalytic system is effective in enhancing the degradation of PCP in contaminated soil suspensions.     

Peptide Washout and Permeability from Glyceryl Monooleate Buccal Delivery Systems

ABSTRACT

Simultaneous evaluation of the permeation and washout of a peptide from the mucoadhesive liquid crystalline phases of glyceryl monooleate (GMO) has been investigated using a donor compartment flow-through diffusion cell. [d-Ala², d-Leu⁵]enkephalin (DADLE) was incorporated into the cubic and lamellar liquid crystalline phases of GMO and applied to excised porcine buccal mucosa mounted in the donor compartment flow-through cell. Phosphate-buffered saline pH 7.4 (PBS) was pumped across the upper surface of the liquid crystalline phases to mimic salivary flow. The steady-state fluxes of DADLE and GMO from the cubic phase were significantly greater than that from the lamellar phase (P<0.01). There was no statistical difference between the amounts of DADLE and GMO washed out from the lamellar and cubic phases (P>0.05). The donor compartment flow-through diffusion cell was found to be a useful tool to evaluate the impact of salivary washout on mucoadhesive oral mucosal delivery systems.