Effect of Anions on Adsorption of Bile Salts by Colestipol Hydrochloride

The Langmuir affinity constant and adsorptive capacity for the adsorption of citrate anion or cholate anion by colestipol hydrochloride at pH 7.5, 37°C, were similar. Prior exposure of colestipol hydrochloride to citrate anion caused the adsorption of cholate anion to decrease slightly in comparison to a control utilizing only cholate anion. The concentration of citrate anion was found to be directly related to the decrease in cholate anion adsorption. Simultaneous exposure of colestipol hydrochloride to citrate and cholate anions at pH 7.5, 37°C, resulted in the same adsorption of cholate anion as sequential exposure to citrate anion followed by cholate anion. Sequential exposure of colestipol hydrochloride to simulated gastric fluid and simulated intestinal fluid containing cholate anion resulted in a small decrease in cholate adsorption which was attributed to competition with phosphate anion in simulated intestinal fluid. Pepsin in the simulated gastric fluid did not affect adsorption of cholate anion from simulated intestinal fluid. Preexposure to components of tomato juice and orange juice also slightly reduced the adsorption of cholate anion by colestipol hydrochloride.     

The in vitro adsorption of some antibiotics on antacids.

The adsorption of oxytetracycline hydrochloride, tetracycline hydrochloride, doxycycline hyclate, triacetyloleandomycin, chloramphenicol, ampicillin, and cloxacillin sodium was studied on various antacids namely, magnesium trisilicate, magnesium oxide, calcium carbonate, bismuth oxycarbonate, aluminium hydroxide, and kaolin. The adsorption of the various antibiotics by milk was also tested as milk is frequently used as an antacid. Charcoal was included in the present study as a model adsorbent having a large hydrophobic surface. The adsorption of the various antibiotics on the different antacids and other adsorbents in most cases obeyed the Freundlich adsorption isotherm. Magnesium trisilicate and magnesium oxide showed the highest adsorptive capacity, relative to other antacids used, for most antibiotics. Calcium carbonate and aluminium hydroxide and intermediate power while kaolin and bismuth oxycarbonate had the least adsorptive power. Charcoal exhibited a marked adsorption for all antibiotics tested. Tetracyclines were found to be more highly adsorbed than other antibiotics studied. Triacetyloleandomycin and chloramphenicol had intermediate values. Ampicillin was only adsorbed to a slight extent while cloxacillin was not adsorbed on the antacids used. The extent of adsorption was correlated to the structure of both the adsorbent and adsorbate, the pH of the adsorbent suspension, and to the polarity of the antibiotic in such pH. The reversibility of the adsorption process was studied in different media and at pH values similar to those of the gastrointestinal tract. The extent of elution was found to be inversely proportional to the adsorptive capacity of the different adsorbents. In general, 0.0143 n NaHCO3 solution was found to possess higher eluting properties than 0.01 n HCl. An exception to this pattern was observed with tetracyclines adsorbed on aluminium hydroxide where the elution with acid resulted in a higher degree of desorption. Careful in vitro and in vivo testing of drug availability is advisable prior to the concomitant administration of antibiotics with antacids or other adsorbents.     

Freeze Drying Properties of Some Oligonucleotides

The purpose of this study was to elucidate the mechanism(s) of adsorption of benzalkonium chloride (BAK) by filter membranes and to determine the effect of formulation and processing parameters on the adsorption of BAK. Six different sterilizing grade filter membranes were used in this study. Adsorption was monitored by passing an aqueous solution of BAK at pH 6 through a 47-mm (14.2 cm² effective filter area) disk filter membrane and measuring the UV absorption of the filtrate with a UV micro flow cell. Hydrophobic and/or electrostatic forces were chiefly responsible for adsorption. The adsorption properties of each filter membrane could be related to its composition. Membranes that were hydrophilic and nonionic or hydrophilic and cationic adsorbed little BAK. However, membranes that were hydrophobic or anionic exhibited significant BAK adsorption. Adsorption followed the Langmuir equation and adsorptive capacities ranged from 116 to 429 μg/47 mm membrane (8.17–30.23 μg/cm²). Formulation factors studied included the concentration of BAK, the presence of a tonicity-modifying agent (sodium chloride, mannitol, glycerin), and the presence of a chelating agent (edetate disodium). The greatest increase in adsorption of BAK occurred when sodium chloride or edetate disodium was used with membranes that contained cationic sites. The effects of flow rate, temperature, autoclaving, interrupting the flow, and presaturating the filter membrane were the processing parameters studied. The rate of adsorption was inversely related to flow rate and the extent of adsorption was inversely related to temperature. Presaturation of the filter membrane with BAK was an effective method to reduce the adsorption of BAK during filtration.     

Adsorption of benzalkonium chloride by filter membranes: mechanisms and effect of formulation and processing parameters

The purpose of this study was to elucidate the mechanism(s) of adsorption of benzalkonium chloride (BAK) by filter membranes and to determine the effect of formulation and processing parameters on the adsorption of BAK. Six different sterilizing grade filter membranes were used in this study. Adsorption was monitored by passing an aqueous solution of BAK at pH 6 through a 47-mm (14.2 cm2 effective filter area) disk filter membrane and measuring the UV absorption of the filtrate with a UV micro flow cell. Hydrophobic and/or electrostatic forces were chiefly responsible for adsorption. The adsorption properties of each filter membrane could be related to its composition. Membranes that were hydrophilic and nonionic or hydrophilic and cationic adsorbed little BAK. However, membranes that were hydrophobic or anionic exhibited significant BAK adsorption. Adsorption followed the Langmuir equation and adsorptive capacities ranged from 116 to 429 micrograms/47 mm membrane (8.17-30.23 micrograms/cm2). Formulation factors studied included the concentration of BAK, the presence of a tonicity-modifying agent (sodium chloride, mannitol, glycerin), and the presence of a chelating agent (edetate disodium). The greatest increase in adsorption of BAK occurred when sodium chloride or edetate disodium was used with membranes that contained cationic sites. The effects of flow rate, temperature, autoclaving, interrupting the flow, and presaturating the filter membrane were the processing parameters studied. The rate of adsorption was inversely related to flow rate and the extent of adsorption was inversely related to temperature. Presaturation of the filter membrane with BAK was an effective method to reduce the adsorption of BAK during filtration.     

Polymeric sorbents for bile acids. I: Comparison between cholestyramine and colestipol.

Isotherms for the sorption of bile acids at 20 degrees C, in tris(hydroxymethyl)aminomethane.HCl(tris) and KH2PO4-NaOH (phosphate) buffers (pH 7.4), indicate that the binding by cholestyramine and colestipol is mainly through ionic linkages, although hydrophobic interactions are also of importance. Cholestyramine has a higher sorption capacity for bile acids, in both buffers, than colestipol. The chloride form of cholestyramine has a higher capacity for cholate in tris buffer than the iodide form. Increased ionic strength of the medium leads to decreased amounts of sorption.     

Fabrication of porous polyethyleneimine-functionalized chitosan/Span 80 microspheres for adsorption of diclofenac sodium from aqueous solutions

Porous surface-modified microspheres can have widespread applications in the removal of wastewater pollutants. In this study, using a nonionic surfactant (Span80) as the pore-forming agent and Zr⁴⁺ as the cross-linking agent, polyethyleneimine (PEI)-modified porous CYCTS/Span80 microspheres ((CYCTS/Span80)-@-PEI) were successfully prepared for the adsorptive removal of diclofenac sodium (DS) from wastewater. The adsorbent was characterized using Fourier-transform infrared spectroscopy, energy-dispersive X-ray spectrometry, scanning electron microscopy, and X-ray diffractometry. The activity of the porous (CYCTS/Span80)-@-PEI microspheres as adsorbents of DS was investigated by varying the experimental parameters (i.e., adsorbent dosage, adsorbent ratio, pH, contact time, temperature, and pollutant concentration). A possible adsorption mechanism was also discussed. The experimental results showed that the adsorption process followed a pseudo-second order kinetic model and the Langmuir adsorption isotherm model, in addition to the Freundlich isotherm model, indicating that the porous structure allowed multi-layer adsorption. Adsorption equilibrium was reached after 240 min at pH 5 and 303 K, yielding a maximum adsorption capacity of 572.67 mg/g. After five adsorption cycles, the removal rate of DS remained >80%, and the recovery rate was high. Therefore, we concluded that the porous (CYCTS/Span80)-@-PEI microspheres are efficient and inexpensive candidates for the removal of DS from wastewater.     

Ciproflexacin-loaded polyisobutylcyanoacrylate nanoparticles: Preparation and characterization

Experimental conditions for attachment of ciprofloxacin hydrochloride to poly(isobutylcyanoacrylate) (PIBCA) nanoparticles (NP) and release of drug were studied. Attachment of the drug was performed by the incorporative and adsorptive processes. The pH, and to a lesser degree the drug concentration in the reaction medium, were shown to be important factors in controlling the size of NP only in the incorporative process. The diameter of NP increased when the initial drug concentration was higher than 1.2 mg/ml. Ciproflaxacin content of NP was influenced by the drug concentration in the polymerization and incubation media. The binding capacity in the adsorptive process was not influenced by the pH. In contrast, the entrapment of ciprofloxacin in the NP by incorporation was greatly influenced by the pH in the range 1.5-4. Thin layer chromatography (TLC) of NP prepared by incorporation showed new products suggesting interactions between ciprofloxacin and isobutylcyanoacrylate. Ciprofloxacin release from nanoparticles prepared by the incorporating process was found to be slower as compared to nanoparticles produced by adsorptive process from which the drug release was practically complete within 1 h in absence of esterases in the release medium. Drug release from the two types of NP was accelerated in the presence of esterases in the release medium.     

Absorption of sodium pentobarbital by three types of activated charcoal

The in vitro adsorption of sodium pentobarbital by activated charcoal (USP), Darco G-60 and SuperChar was studied. Various solutions of sodium pentobarbital, ranging in concentration from 2.5 to 10 mg/ml (pH = 9), were prepared in distilled water. Radiolabeled (14C) sodium pentobarbital was added to serve as a concentration marker. Two millimeters of each solution was added to from 5 to 350 mg of each charcoal in a test tube. The resulting charcoal-drug slurries were mixed thoroughly and incubated at 37 C for 10 min. Analysis of supernatant allowed calculation of percentage of drug bound. Plots of percentage of drug bound vs log quantity of charcoal necessary to bind 50% of the drug (B-50) were constructed. B-50 was lowest for SuperChar (indicating highest binding capacity), followed by USP and Darco G-60 activated charcoals. In a second series of experiments, drug adsorption was determined at various pH's, or when sodium pentobarbital was dissolved in various volumes of distilled water. Adsorption of the drug from solutions buffered at pH 8.1, 9, 9.7, 11 and 12 did not differ from adsorption in aqueous solution. Adsorption of sodium pentobarbital by 50 or 100 mg of each charcoal did not change when 5 mg of the drug was dissolved in 1, 2, 4, 6, 8 or 10 ml of water. The results suggest that sodium pentobarbital is most readily adsorbed by SuperChar under all conditions studied, followed by USP and Darco G-60 activated charcoals. Changes in pH, or in the initial mixture volume, did not influence the degree of drug adsorption to activated charcoal.     

Quaternized colestipol, an improved bile salt adsorbent: in vitro studies

Colestipol.HCl (col-HCl) was quaternized with methyl iodide to form col-CH3l. The in vitro binding capacities of the quaternized and protonated resins in water and in Tris-HCl buffer (0.0015 and 0.0025 M, pH 7.0) at approximately 22 degrees C for sodium glycocholate (NaGC) was determined by reversed-phase HPLC. The binding capacities were found to depend on the adsorption medium. In water, the binding capacity of col-CH3l was 30% greater than that of its protonated form. In Tris-HCl buffer at pH 7.0, the binding capacities of the resins were similar. When the quaternized colestipol was converted to its chloride form, the binding capacity for NaGC in Tris-HCl increased significantly and was 30% greater than that for its protonated analogue. In Cotazym 65B-water, a medium used to test the binding capacity of the resins in the presence of various agents (to try to simulate intestinal conditions), the binding capacity of the quaternized resin was again greater than that of its protonated form. Quaternization thus increases the in vitro binding capacity of colestipol for the glycocholate anion.     

Study of interaction of gastrointestinal agents in the presence of cytoprotective drugs. Part II. In vitro study on the adsorption of selected spasmolytic drugs on sucralfate

The subject of the research was the adsorption of selected musculotropic and cholinolytic spasmolytics on a cytoprotective drug--sucralfate. Adsorption evaluation was made by a static method, in vitro, the environment reaction, the concentrations of the tested drugs and the sucralfate form being taken into account. The obtained results prove that the analysed therapeutic substances are adsorbed on the sucralfate in all pH. The highest bonding capacity was observed in tests at pH=3.6, in the presence of sucralfate, which at this pH occurs in the form of suspension. The lowest capacity was at pH=1.5 in the presence of sucralfate in the paste form. In the group of the tested drugs, scopolamine butylbromide is adsorbed best, drotaverine hydrochloride little less and papaverine hydrochloride least of all.     

Adsorption of Salmon Calcitonin to PLGA Microspheres

Purpose. The interaction of salmon calcitonin (sCT) and poly (d,l-lactide-co-glycolide) was detected during preparation and evaluation of microspheres. The purpose of this study was to quantitate the extent and nature of the interaction. Methods. Blank microspheres were prepared by an aqueous emulsification solvent extraction technique. Adsorption studies were carried out at six concentrations of sCT and three concentrations of microspheres. Adsorption isotherms were constructed using the Langmuir and Freundlich treatments. Results. Adsorption at 1 mg/ml sCT concentration resulted in almost complete depletion of the peptide from the adsorption medium with the time to reach maximum adsorption decreasing with increasing microsphere concentration. At sCT concentrations below 100 µg/ml, a true equilibrium occurred in 1 hour or less while at higher concentrations (up to 350 µg/ml), a transient equilibrium was reached in 1 to 2 hours, followed by further adsorption of the peptide. The adsorption followed the Langmuir isotherm at concentrations below 200 µg/ml, indicating formation of a monolayer. Multilayer interaction, described by the Freundlich isotherm, occurred at higher concentrations and resulted in complete depletion of sCT from the adsorption medium. The affinity constant during monolayer formation was 0.09 and the plateau surface concentration was 5.1 µg/mg. The multilayer peptide-peptide adsorption showed a lower affinity (0.025) but higher capacity (24 µg/mg) than the monolayer peptide-polymer adsorption. Conclusions. The results show that poly (d,l-lactide-co-glycolide) microspheres have a high adsorption capacity for sCT which must be considered in formulating a controlled delivery product of this peptide.     

In-vitro study of the drug interactions between Miglitol, an alpha-glucosidase inhibitor, and adsorbents

The interactions between miglitol, an alpha-glucosidase inhibitor, and six adsorbents (carbon spheres, cholestyramine, colestimide, sevelamer hydrochloride, calcium polystyrene sulfonate, and sodium polystyrene sulfonate) were investigated in vitro. Miglitol corresponding to the minimum dose and adsorbents corresponding to the maximum dose were incubated at 37 degrees C for 180 min in solutions of pH 1.2 (gastric pH condition) and pH 6.8 (enteric pH condition), with and without the presence of carbohydrates, which were added to observe the effects on food adsorption. The adsorption ratio of miglitol to carbon spheres was 13.6% and 0% in pH 1.2 solution and 86.4% and 5.0% in pH 6.8 solution without and with the presence of carbohydrates, respectively. Thus, the adsorption ratio was higher in pH 6.8 solution. Adsorption of miglitol to calcium polystyrene sulfonate was nearly the same, 15.0-21.9%, at both pH. The adsorption ratio of miglitol to sodium polystyrene sulfonate was 43.4% and 45.5%, respectively, in pH 1.2 solution without and with carbohydrates. In the pH 6.8 solutions, however, the respective adsorption ratios were low (5.2% and 11.3%). Miglitol did not adsorb to cholestyramine, sevelamer hydrochloride or colestimide under any pH condition examined. The above results suggest that miglitol adsorbs to carbon spheres and polystyrene sulfonic acid cation exchange resins. However, considering that miglitol is taken just before eating and thus exists in gastointestinal fluids together with food, and that the site of its effect is the upper small intestine, the interactions between miglitol and these adsorbents will most likely not be a problem.     

The effect of colestipol on digitoxin plasma levels.

The effect of colestipol (colestipol hydrochloride; U-26 597 A), a copolymer of tetraethylenepentamine and epichlorhydrine, on plasma digitoxin levels has been investigated. Recently, it has been stated that colestipol decreases the enterohepatic circulation and the plasma half-life of digitoxin. Colestipol was administered to 11 patients having a digitoxin plasma level which is generally accepted to be above the therapeutic range (greater than 40 ng/ml). The elimination rate of digitoxin measured by serial radioimmunoassay in these colestipol treated patients was compared with the elimination rate of digitoxin in 11 patients not treated with colestipol. The results of this study did not demonstrate a significant difference in the mean (+/- S.D.) digitoxin plasma half-life between the colestipol treated (6.3 +/- 1.3 days) and the non-colestipol treated patients (6.8 +/- 1.0 days).     

In vitro investigation of sodium diclofenac adsorption on sucralfate

Adsorption of sodium diclofenac was investigated in the presence of sucralfate--a cytoprotective agent preventing gastropathy, adverse effect of diclofenac. Evaluation of adsorption was performed by means of a static method in vitro taking into account pH of the environment, temperature, concentration of the investigated agents and the form of sucralfate. Findings obtained prove that sodium diclofenac is adsorbed on sucralfate in all investigated pH ranges and the capability of sucralfate binding depends on its form, temperature and environmental pH. The highest binding was observed at pH 5.0 in the presence of sucralfate, which at this pH has the form of a suspension, while the lowest--at pH 1.5 in the presence of sucralfate in the form of paste. Low values of adsorption temperature of diclofenac as well as the relationship between the level of its adsorption and environmental pH are the dominating factors pointing to the physical and exothermic adsorption.     

Adsorption of d-Nal(2) 6LHRH,a decapeptide,onto glass and other surfaces

Adsorption patters of aqueous solutions of d-Nal(2) ⁶LHRH onto glass, plastic, tubing, syringes and filters were characterized. Effects of ionic species, inert proteins and amino acids on the extent of adsorption onto glass surfaces were also studied. Among the different additives, the phosphate ion at 0.1 M concentration and the acetate ion at 0.16 M concentration, both at pH 5, were the most effective in preventing adsorption onto glass. Siliconization of the glass surface did not inhibit adsorption suggesting that adsorption was not solely due to ionic amine-silanol binding. Adsorption to filters and syringes varied depending on the brand of filters and syringes used, whereas adsorption onto plastic bottles and tygon tubing was minimal.     

Determination of trimetazidine HCl by adsorptive stripping square-wave voltammetry at a glassy carbon electrode.

The adsorptive and electrochemical behavior of trimetazidine hydrochloride on a glassy carbon electrode were investigated in acetate buffer solution by using cyclic and square-wave voltammetry. Cyclic voltammetric studies indicated the oxidation of trimetazidine hydrochloride at the electrode surface through a single two-electron irreversible step and fundamentally controlled by adsorption. The solution condition and instrumental parameters were optimized for the determination of the authentic drug using adsorptive square wave stripping voltammetry. Trimetazidine hydrochloride gave a sensitive adsorptive oxidative peak at 0.750 V (vs. Ag/AgCl). The oxidation peak was used to determine authentic trimetazidine hydrochloride concentration in the range 5.0 x 10(-8)-5.0 x 10(-6) M with a detection limit of 2.0 x 10(-8) M. The procedure was successfully applied for assay of trimetazidine hydrochloride in the tablet dosage form (Vastarel). A mean recovery of 94.7% with a relative standard deviation (R.S.D.) of 0.88% was obtained. Applicability to assay the drug in urine samples was illustrated. The peak current was linear with the drug concentration in the range 17-85 microg per ml urine. The detection limit was 1.7 microg ml(-1) urine.     

In vitro adsorption of mebeverine hydrochloride onto kaolin and its relationship to pharmacological effects of the drug in vivo

The in vitro uptake of mebeverine hydrochloride from an initial drug concentration of 0.25–4.25 or 0.2–3.6 g% w/v onto kaolin 5.0 g% w/v at pH 1.8 or 7.5, respectively, at 37 °C was represented by a double-layered adsorption isotherm. The calculated data were in accordance with a Langmuir adsorption isotherm for an initial drug concentration up to 2.1 or 2.0 g% w/v when a monolayer was formed at pH 1.8 or 7.5, respectively. The adsorption process is pH dependent, and is affected by the electrolyte concentration and valency. The amount of the drug desorbed (mg% w/v) by washing with different elution media at 37 °C followed the sequence 0.1 M hydrochloric acid>0.1 M magnesium chloride>0.1 M sodium chloride>simulated intestinal fluid. The results obtained from this study indicate that two mechanisms, ion exchange and physical adsorption, were involved in the uptake of mebeverine hydrochloride by kaolin. The presence of different concentrations of kaolin with the tablets or capsules of the drug, adversely affected the release rate. The in vivo and in vitro studies on guinea pig ileum showed that the presence of kaolin in a mixture with mebeverine hydrochloride did not affect to any significant level the inhibiting effect of the musculotropic drug on carbachol-induced contractions in the isolated guinea pig ileum. In vivo studies showed similar results for barium chloride as well.     

In-vitro adsorption studies of isoniazid.

In-vitro experiments were performed to investigate the extent of adsorption of isoniazid to activated charcoal and locally produced activated carbon black (N220) and to explore the effect of varying pH on this adsorption. The results of the study indicated that activated charcoal and activated carbon black adsorbed isoniazid effectively. Adsorption was dependent upon the quantity of charcoal used. With charcoal quantity at 0.5 g, adsorption was virtually completed within 60 min. The mean or composite adsorption capacity of activated charcoal and activated carbon black (microgram ml-1 of charcoal) were 325 and 278, respectively. The result of adsorption isotherms indicated no change in binding capacity of the drug from solutions of different pH.     

Controlled release of terbinafine hydrochloride from pH sensitive poly(acrylamide/maleic acid) hydrogels

Adsorption and controlled release of terbinafine hydrochloride (TER-HCl) to and from pH sensitive poly(acrylamide/maleic acid) (P(AAm/MA)) hydrogels were investigated. P(AAm/MA) hydrogels were prepared by irradiating the ternary mixtures of AAm/MA/and water by gamma-rays at ambient temperature. Antifungal drug, TER-HCl containing hydrogels, at different drug to polymer ratios, was prepared by direct adsorption method. The influence of MA content in the gel on the adsorption capacities of hydrogel and the effect of pH on the releasing behavior of TER-HCl from gel matrix were investigated. Terbinafine adsorption capacity of hydrogels are found to increase from 2 to 38 mg TER-HCl per g dry gel with increasing amount of MA in the gel system. In vitro drug release studies in different buffer solutions show that the basic parameters affecting the drug release behavior of hydrogel are the pH of the solution and MA content of hydrogel.     

Loading of Tetanus Toxoid to Biodegradable Nanoparticles from Branched Poly(Sulfobutyl-Polyvinyl Alcohol)-g-(Lactide-Co-Glycolide) Nanoparticles by Protein Adsorption: A Mechanistic Study

Purpose. Mucosal delivery of vaccine-loaded nanoparticles (NP) is an attractive proposition from an immunologic perspective. Although numerous NP preparation methods are known, sufficient antigen loading of NP remains a challenge. The aim of this study was to evaluate adsorptive loading of NP with a negatively charged surface structure using tetanus toxoid (TT) as a model vaccine. Methods. Blank NP, consisting of poly(sulfobutyl-polyvinyl alcohol)-g-(lactide-co-glycolide), as well as poly(lactide-co-glycolide) NP were prepared by a solvent displacement technique. The use of polymers with different degrees of substitution resulted in NP with different negative surfaces charges. Adsorption of TT to NP was performed varying to NP surface properties, protein equilibrium concentration, and loading conditions. Results. The protein adsorption was controlled by NP surface properties, and maximum TT adsorption occurred at highly negatively charged NP surfaces. Results from isothermal titration calorimetry and -potential measurement suggest an adsorption process governed by electrostatic interactions. The adsorption followed the Langmuir isotherm in the concentration ranges studied. TT withstood this gentle loading procedure in a nonaggregated, enzyme-linked immunoabsorbant assay-active form. Conclusions. The results demonstrate that negatively charged NP consisting of poly(sulfobutyl-polyvinyl alcohol)-g-(lactide-co-glycolide) are suitable for adsorptive loading with TT and may have potential for mucosal vaccination.