[Show abstract][Hide abstract]ABSTRACT: The present study aimed to evaluate the suitability of Smopex-102 cation-exchange fiber for the separation of acidic and basic model drugs from biological fluids (e.g. serum) prior to chromatographic analysis. In addition, the interactions of the drugs with the fiber were studied. The study found that basic antidepressant model drugs bound to a considerably greater extent than acidic drugs to poly(acrylic acid) (PAA) grafted Smopex-102 cation-exchange fiber from 25 mM HEPES buffer (pH 7.0) and spiked serum. Drug binding from serum decreased except for acidic drugs due to drug distribution between serum proteins and cation-exchange fiber. Electrostatic interactions were possibly the most important factors affecting drug binding to the fiber. Basic drugs were released most effectively from the fiber by using acetic acid (mean released amount 123.7 +/- 36.3% and mean absolute recovery 95.4 +/- 23.8%). Results demonstrated that the cation-exchange fiber evaluated might be a potential material for separating basic drugs from protein-free and proteinaceous (e.g. serum) liquid solutions for subsequent monitoring and evaluation. However, the drug release solution and release time must be optimized more precisely in order to validate described sample preparation method for each basic drug.
Full-text available · Article · Feb 2009 · Pharmazie
[Show abstract][Hide abstract]ABSTRACT: This study investigated the influence of pH of adsorption medium and co-adsorptive metal cations for the adsorption of potassium
(K+) and magnesium (Mg2+) ions onto poly (vinylidene fluoride) grafted poly(acrylic acid) (PAA-PVDF) membrane. At pH 4.8, the adsorption of potassium
and magnesium was minimal, because of nearly non-dissociated carboxylic acid groups of PAA-chains, but adsorption increased
with increasing ion concentration. The interaction of the studied cations between PVDF-PAA membranes increased considerably
at pH 7.0 the dissociation of carboxylic acid groups of PAA. The addition of ionic substances (calcium (Ca2+) and sodium (Na+) to the adsorption medium reduced the adsorption of potassium and magnesium onto the membrane, because of co-adsorption.
Divalent calcium reduced more effectively than univalent sodium the adsorption of potassium and magnesium onto the membrane.
In conclusion, co-adsorbing ions reduced the adsorbed amount of potassium and magnesium ions due to binding competition. The
percentual adsorbed values suggest that adsorption affinity of studied ions onto the PVDF-PAA membrane followed the order
Na+ < K+ < Mg2+ < Ca2+. The effect of metal cations on drug adsorption from biological fluids needs research in the future, because e.g. PVDF-PAA
membrane has been used in drug separation processes.
Full-text available · Article · Jan 2009 · Journal of Polymer Research
[Show abstract][Hide abstract]ABSTRACT: Isolation of acidic and basic model drugs by using pH sensitive poly(acrylic acid) grafted poly(vinylidene fluoride) (PAA-PVDF) cation-exchange membrane from biological fluids was reported. Effects of drug charge and lipophilicity on adsorption were also investigated. In the present study, basic model drugs adsorbed to a considerably greater extent onto the membrane than acidic drugs. Albumin was not adsorbed onto the membrane. Results of our study exposed, that electrostatic interactions between positively charged basic drug and negatively charged PVDF-PAA membrane were the most important factor affecting drug adsorption onto the membrane. Adsorption of acidic and basic drugs onto the PVDF-PAA membrane was not related to drug lipophilicity. The results of present study demonstrated that basic drugs adsorbed extensively onto the membrane, but albumin did not, proposing that PAA-PVDF membrane may be suitable for isolating basic drugs from proteinaceous biological fluids (i.e. serum) for subsequent monitoring and evaluation.
Full-text available · Article · Oct 2007 · European Journal of Pharmaceutics and Biopharmaceutics
[Show abstract][Hide abstract]ABSTRACT: The influence of charge and lipophilicity of acidic and basic model drugs on their adsorption onto poly(N,N-dimethyl aminoethyl methacrylic acid) grafted poly(vinylidene fluoride) (DMAEMA-PVDF) membranes was evaluated. The effect of serum proteins (albumin, IgG) and hormones (cortisol, free thyroxine (T(4)F) and thyrotropin (TSH)) on drug adsorption was also studied. Acidic model drugs (antiepileptics and benzodiazepies) adsorbed to a greater extent onto the membrane from Hepes buffer at ionic strength of 25mM and pH 7.0 than basic drugs (antidepressants) did. Adsorption of acidic model drugs was based on electrostatic interactions between positively charged tertiary amino groups of DMAEMA side-chain and acidic negatively charged drug. Albumin diminished the adsorption of drugs from serum onto the membrane. Lipophilicity was related to the adsorption of acidic model drugs from serum onto the membrane. The degree of grafting had the greatest effect on adsorption of lipophilic drugs, but no influence was observed on adsorption of hydrophilic drugs. The present results showed that acidic drugs and albumin adsorbed onto the membrane, which suggests that the PVDF-DMAEMA membrane may be suitable for separating acidic drugs from protein-free substances for subsequent monitoring and evaluation.
Article · Jul 2007 · International Journal of Pharmaceutics
[Show abstract][Hide abstract]ABSTRACT: The effect of environmental ionic strength on the rate of drug release from a cation exchange membrane was evaluated. Cationic propranolol-HCl, timolol, sotalol-HCl, atenolol and dexmedetomidine-HCl and neutral diazepam were adsorbed onto a porous poly(vinylidene fluoride) (PVDF) membrane that was grafted with bioadhesive poly(acrylic acid) chains (PAA-PVDF). Despite its porosity, the PAA-PVDF membrane acted as a cation exchange membrane. The release of adsorbed drug from the PAA-PVDF membrane was investigated by using a USP rotating basket apparatus. Adsorption of cationic drugs onto the PAA-PVDF membrane tended to increase with increasing lipophilicity of the drug. A decrease in the ionic strength of the adsorption medium increased the amount of the cationic drugs adsorbed onto the membrane, but had no effect on diazepam adsorption. The release of cationic drugs from the PAA-PVDF membrane was greatly affected by the ionic strength of both the adsorption medium and the dissolution medium, while ionic strengths did not affect diazepam release. Our results suggest that the ionic strength of both the adsorption and dissolution media substantially affects the release rate of a drug that has been adsorbed onto the ion exchange membrane, primarily via electrostatic interactions, while ionic strength has no effect on the release of a drug which has been adsorbed onto the membrane via non-electrostatic forces.
[Show abstract][Hide abstract]ABSTRACT: The influence of pH, ionic strength and the concentration of albumin in the adsorption medium as well as the charge and lipophilicity of a model drug on their adsorption onto poly(acrylic acid) grafted poly(vinylidene fluoride) (PAA–PVDF) membranes was evaluated. The PAA–PVDF membrane is a responsive porous polymer membrane that we have studied for controlled drug delivery. Sodium salicylate (anionic), flunitrazepam (neutral), primidone (neutral), desipramine (cationic) and thioridazine (cationic) were used as model drugs. The extent of drug adsorption was dependent on pH. Drug adsorption was enhanced by the dissociation of the grafted PAA chains and by a positive charge and a high lipophilicity of the drug. Increasing the ionic strength of the medium retarded the adsorption of the cationic drugs. Interestingly, the present results showing that drugs are adsorbed onto the membrane while albumin is not adsorbed onto the membrane suggest that the PAA–PVDF membrane may be suitable for separating drugs from proteinaceous substances for subsequent monitoring and evaluation.
Article · Dec 1999 · European Journal of Pharmaceutical Sciences
[Show abstract][Hide abstract]ABSTRACT: Ion exchange resins have several applications in pharmacy for controlled or sustained release of drugs. In the present study, effects of the ionic strengths of adsorption medium and dissolution medium on drug adsorption onto and release from a acrylic acid grafted poly(vinylidene fluoride) (PAA-PVDF) were studied. Despite their porosity, PAA-PVDF membranes act reasonable well as cation exchange membranes. It was observed, that ionic strength of adsorption medium, degree of grafting and concentration of propranolol-HCl in adsorption medium affect propranolol-HCl adsorption onto the membrane. The fluxes of smaller molecules (MW < 500) across the membrane decreased with ionic strength of buffer solution, whereas the fluxes of the large molecules (FITC-dextran, MW 4400) increased with ionic strength. Release rate of adsorbed propranolol-HCl from the membrane into phosphate buffer was greatly affected by ionic strength of adsorption medium. These results can be explained by a cation exchange process between membrane and cations present in the buffer solution and swelling behavior of the grafted PAA chains.
Article · Feb 1999 · International Journal of Pharmaceutics
[Show abstract][Hide abstract]ABSTRACT: Poly(N-isopropylacrylamide) (poly(NIPAAm)) is a temperature sensitive polymer, which has been used in the development of thermally controlled devices. In the present study, poly(NIPAA)m grafted poly(vinylidene fluoride) (PVDF) membranes were prepared by an irradiation method and fluxes of model compounds across the various grafted membranes were measured. The effectiveness of various grafted membranes to control drug fluxes by temperature was studied using FITC-dextrans (molecular weights 4400–50 600) and mannitol as model compounds. Also, the effect of environmental conditions on the LCST of the membrane was evaluated. The fluxes of bigger molecules across a temperature sensitive, porous poly(NIPAA)m–PVDF membranes were effectively controlled by temperature, environmental ionic strength and degree of grafting of the membrane, while flux of the smaller molecules was not controlled thermally even at high degree of membrane grafting. These result indicates that the studied membranes are useful in controlling the permeation of high molecular weight compounds such as polynucleotides, peptides and proteins.
Article · Apr 1998 · International Journal of Pharmaceutics
[Show abstract][Hide abstract]ABSTRACT: Porous ion exchange membranes have potential applications for drug delivery systems. Permeability of these membranes can be controlled by environmental factors like pH and ionic strength but also the drug properties have an important role in the permeation process. In this paper the influence of the drug charge, lipophilicity and molecular weight on the diffusional drug flux is demonstrated. The membranes under study were poly(acrylic acid) (PAA) grafted porous poly(vinylidene fluoride) (PVDF) membranes which are cation selective due to the partial ionization of carboxyl groups in grafted PAA chains. At low pH the membrane pores are open and the drugs can diffuse through the membrane quite easily. However, at pH 7 the grafted chains partially block the pores and the diffusional flux of bigger drug molecules (Mw9400) decreases five orders of magnitude and also the flux of smaller molecules is clearly reduced. When the influence of the drug charge on the diffusion of the drugs across the membranes was studied, it turned out that the PAA-PVDF membranes facilitate the transport of cationic drugs and repel anionic ones. The presented mathematical model, based on Donnan drugs equilibrium and measured transport number data, predicted the observed trends reasonably well.
Article · Feb 1998 · Journal of Controlled Release