Influence of different parameters on drug release from hydrogel systems to a biomembrane model. Evaluation by differential scanning calorimetry technique (original) (raw)
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European Journal of Pharmaceutical Sciences, 2008
Hydrogels Dimyristoylphosphatidylcholine Differential scanning calorimetry Drug release a b s t r a c t Inulin has been derivatized with methacrylic anhydride (MA) and succinic anhydride (SA) to obtain a methacrylated/succinilated derivative (INU-MA-SA) able to produce a pH sensitive hydrogel after UV irradiation. The hydrogel was characterized and loaded with diflunisal (10.4, 17 and 24%, w/w) chosen as a model drug. The drug release from INU-MA-SA-based hydrogel to a biomembrane model made by unilamellar vesicles of dimyristoylphosphatidylcholine (DMPC) was investigated at pH 4.0 and 7.4 by differential scanning calorimetry (DSC)
Thermochimica Acta, 2004
A comparative study on the ability of various polymers to interact with a biomembrane model was carried out by differential scanning calorimetry (DSC). The investigated samples were a water soluble polymer, the ␣,-polyaspartylhydrazide (PAHy) and its derivatives containing polyethylene glycol (PEG 2000 ) (sample PAHy-PEG 2000 ), or hexadecylamine (C 16 ) (sample PAHy-C 16 ) or both compounds (sample PAHy-PEG 2000 -C 16 ). Some samples are able to arrange themselves as micellar structures and to interact potentially with the membrane surface so as to favor the release of the drug near the target membrane and consequently to improve drug adsorption processes. First, the interaction of all polymers with a biomembrane model made of multilamellar vesicles of mixed (80:20, mol:mol) dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidic acid (DMPA), has been studied (pH 7.4), then the interaction of Ketoprofen (KPF) as free drug or released from PAHy-C 16 micelles with the same biomembrane model has been investigated. Differential scanning calorimetry appears to be a suitable technique to follow the interaction of all prepared samples as well as the transfer kinetics of a drug from PAHy-C 16 micelles to a biomembrane model. The drug release kinetics, from PAHy-C 16 micelles, was compared with the transfer of free drug (after dissolution from a solid form) by evaluating their effects on the thermotropic behavior of DMPC/DMPA multilamellar vesicles.
Characterisation and controlled drug release from novel drug-loaded hydrogels
European Journal of Pharmaceutics and Biopharmaceutics, 2008
Hydrogel based devices belong to the group of swelling controlled drug delivery systems. Temperature responsive poly(N-isopropylacrylamide)-poly(vinylpyrrolidinone) random copolymers were produced by free radical polymerisation, using 1-hydroxycyclohexylphenyketone as an ultraviolet-light sensitive initiator, and poly(ethylene glycol) dimethacrylate as the crosslinking agent (where appropriate). The hydrogels were synthesised to have lower critical solution temperatures (LCST) near body temperature, which is favourable particularly for 'smart' drug delivery applications. Two model drugs (diclofenac sodium and procaine HCl) were entrapped within these xerogels, by incorporating the active agents prior to photopolymerisation. The properties of the placebo samples were contrasted with the drug-loaded copolymers at low levels of drug integration. Modulated differential scanning calorimetry (MDSC), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and atomic force microscopy (AFM) were used to investigate the influence of the drugs incorporated on the solid-state properties of the xerogels. MDSC and swelling studies were carried out to ascertain their effects on the LCST and swelling behaviour of the hydrated samples. In all cases, drug dissolution analysis showed that the active agent was released at a slower rate at temperatures above the phase transition temperature. Finally, preliminary in vitro cytotoxicity evaluations were performed to establish the toxicological pattern of the gels.
Journal of Applied Polymer Science, 2012
Poly(N-isopropylacrylamide) (PNIPAM) hydrogels were simply prepared by free radical polymerization in different methanol-water mixture. A scanning electron microscopy study revealed that the freeze-dried hydrogels were macroporous. The swelling ratios in water at 20 C of the resulting hydrogels followed the order: X 0.43 >X 0.21 >X 0.76 % X 0.57 >X 0.31 >X 0.13 >X 0.06 >X 0 , where X m denotes a gel prepared in a methanol-water mixture with m mole fraction of methanol (x m ). Below the lower critical solution temperature, the swelling ratio values of all of the hydrogels gradually decreased with the increase in the temperature. The complete collapse of the PNIPAM chain of all the gels occurred at about 38 C, whereas the same was observed at about 35 C for the conventional gel prepared in water. The swelling ratio values of all the PNIPAM gels in the methanol-water mixtures with different x m values at 20 C passed through a minimum in the cononsolvency zone. The deswelling rates of the hydrogels decreased in the following order: X 0.43 > X 0.31 > X 0.21 > X 0.57 > X 0.76 % X 0.13 > X 0.06 > X 0 . The reswelling rates of these hydrogels decreased in the following order: X 0 > X 0.31 > X 0.06 % X 0.13 > X 0.76 > X 0.57 > X 0.21 > X 0.43 . The release rates of the Tramadol Hydrochloride drug at 37 C from the drug-loaded hydrogels were almost same for all of the hydrogels. V C 2012 Wiley Periodicals, Inc. J Appl Polym Sci
Colloids and Surfaces B: …, 2007
Release of calcein and griseofulvin (GRF) from control (gels in which solutes are dissolved in) and liposomal gels was studied using agaroseassisted immobilization as a technique to separate gels from drug-receptor compartments. Liposomes composed of phosphatidylcholine (PC) or distearoyl-glycero-PC and cholesterol (DSPC/Chol), and incorporating calcein or GRF were prepared by thin film hydration. After cleaning the liposomes they were dispersed in different hydrogels (carbopol 974 [1, 1.5 or 2% (w/w)], hydroxylethyl-cellulose (HEC) [4% (w/w)], or a mixture of the two), and release of calcein or GRF was followed by fluorescence or photometric technique, respectively. Results show that calcein release from liposomal gels is slower compared to control gels, and can be further retarded by using rigid-membrane liposomes (faster release from PC-liposome compared to DSPC/Chol-liposome gels). Additionally, calcein release is not affected by the lipid amount loaded (in the range from 2 to 8 mg/ml), therefore solute loading can be controlled according to needs.
To Evaluate and Study the Swelling and Drug Release Behavior of Poly (N-Vinyl-2-Pyrrolidone) Gel
The drug loading and drug release efficiency of the P (N-vinyl-2-pyrrolidone) hydrogel was evaluated using the ketotifen as model drugs. The hydrogel was cut into small discs (3 mm thickness and diameter) and immersed in the solutions of the ketotifen for three days to achieve the maximum (equilibrium) swelling. The hydrogel immersed in 0.1 N HCl and phosphate buffers (pH 6.8) showed the 31.828 % and 29.783 % loading of the ketotifen by weight of the dried hydrogel, respectively that was not significantly difference (p was greater than 0.05). However, the slow swelling behavior of the hydrogel in the acidic medium was observed in the absence of the drug. The method of analysis of ketotifen using U.V-visible spectrophotometer and HPLC was developed for the analysis of these components in the dissolution medium. The methods were linear (r = 0.9967) over the range of 0.1 to 10 µg.ml for ketotifen using U.V Visible spectrophotometer and 2 1 HPLC respectively. The precision, accuracy and reproducibility of the methods were in an agreeable range to analyze the samples obtained from the dissolution medium. The various parameters for the methods of analysis of the ketotifen using spectrophotometer and HPLC methods were validated. The linearity of the method using UV Visible spectrophotometer and HPLC were (r = 0.9967). The release of ketotifen from the P (N-vinyl-2-2 pyrrolidone) hydrogel under acidic condition was only 10 % of the drug released in about 72 hours and followed Higuchi model and drugs were released through Fickian diffusion. The data was best fitted in the Higuchi model (R = 0.9566) indicating the drug release followed Fickian diffusion. The application of the 2 Korsmeyer's equation showed that the release of ketotifen release from the hydrogel disc followed the Fickian diffusion. Under basic conditions (pH 6.8), it was observed that the in-vitro release of ketotifen from hydrogel disc GS2 best fitted to the Hixon-Crowell (0.9917) indicating the erosion and dissolution of hydrogel. As the value of (n) for the GS2 was 1.2634, it indicating that the release of ketotifen from hydrogel disc followed non-Fickian super case II release. Under mixed conditions (for the first two hours in acidic condition (pH 0.1N HCl) and then for the rest of time at (pH 6.8), it was found that the in-vitro release of ketotifen from hydrogel loaded disc GS3 best fitted to the Higuchi model (0.9821) indicating the drug release followed Fickian diffusion. The value (0.9216) of release exponent "n" obtained with Korsmeyer's-Pappas equation suggested that drug release from GS3 formulation followed anomalous transport.
Polymers for Advanced Technologies, 2004
N-Isopropylacrylamide/itaconic acid copolymeric hydrogels were prepared by irradiation of the ternary mixtures of N-isopropylacrylamide/itaconic acid/water by c-rays at ambient temperature. The dependence of swelling properties and phase transitions on the comonomer concentration and temperature were investigated. The hydrogels showed both temperature and pH responses. The effect of comonomer concentration on the uptake and release behavior of the hydrogels was studied. Methylene blue (MB) was used as a model drug for the investigation of drug uptake and release behavior of the hydrogels. The release studies showed that the basic parameters affecting the drug release behavior of the hydrogels were pH and temperature of the solution.
Biocompatibility and drug release behavior of spontaneously formed phospholipid polymer hydrogels
Journal of Biomedical Materials Research Part A, 2007
Hydrogels containing 2-methacryloyloxyethyl phosphorylcholine (MPC) moieties were formed from aqueous solutions with water-soluble MPC polymers with carboxylic acid and alkyl groups because of hydrogen bonding formation. To investigate the biocompatibility and drug release behavior of the hydrogels, we used random-and block-type carboxylic acid MPC polymers, such as poly [MPC-co-methacrylic acid (MA)] (rPMA), poly[MPC-co-4-(2methacryloyloxyethyl) trimellitic acid (MET)] (rPMT), poly (MA-block-MPC-block-MA) (bPMA) and poly(MET-block-MPC-block-MET) (bPMT), and alkyl MPC polymers, such as poly[MPC-con -butyl methacrylate] (PMB) and poly(MPCco-benzyl methacrylate) (PMBz). We investigated the biocompatibility of the spontaneously formed MPC polymer hydrogels by a hemolysis test and an in vivo injection test. The random MPC polymers having carboxylic acid groups expressed more hemolytic activity compared to the block polymers. The results of the in vivo injection test also indicated low biocompatibility of the carboxylic acid polymers especially at high concentration. The alkyl MPC polymers, the PMB and PMBz showed excellent biocompatibility in both hemolysis and in vivo injection test. However, the hydrogels, the rPMA/PMB hydrogel (rABgel) and the rPMT/ PMBz hydrogel (rTZgel) lowered the hemolytic activity of elemental polymers, the rPMA and rPMT. Thus, suppression of the ionization of the carboxylic acid groups is necessary for biocompatibility. We also investigated the drug release behavior with attention to the interaction between the polymer and the drugs. The release behavior of a relatively lowmolecular-weight hydrophilic drug, 5-fluorouracil, did not depend on the structure of the polymers. The higher-molecular-weight drugs, ketoprofen and indomethacin, were released faster from the block polymer hydrogel than the random polymer hydrogel, the rABgel, while the highestmolecular-weight drug, doxorubicin, was released faster from the random polymer hydrogel. A probable reason for this is the difference in the molecular structure; that is, the separated hydrophilic and hydrophobic sections in the block polymers constructed pathways where a drug can diffuse. In addition, the rTZgel suppressed the release of a drug with a large number of aromatic rings probably because of the stacking effect. The results of the compression test also suggested the existence of the stacking effect between the rTZgel and the drugs. Based on these results, control of drug release is possible by selecting a reservoir with an appropriate chemical structure to interact with the drug. For example, release of a relatively linear-structured drug with less aromatic rings can be suppressed in the rABgel rather than in the rTZgel. Thus, it can be concluded that if the ionization is suppressed, these MPC polymer hydrogels can be used as a material for a drug reservoir that can be selected according to the drug.
Drug release with simultaneous dimensional changes from a new copolymeric hydrogel
Polymer, 1994
The diffusional behaviour of sodium salicylate (SSA) from a new chemically crosslinked copolymeric hydrogel of 2-hydroxyethyl methacrylate with N, N'-dimethyl-N-methacryloyloxyethyl-N-(3-sulfopropyl)ammonium betaine is reported. The drug release into water was effected under sink conditions and the kinetics at 310 K were followed by continuous measurement of conductivity. A modified form of Fick's second law has been derived to take into account the dimensional changes of copolymer during drug release, which were measured photographically. The procedure was used to evaluate the diffusion coefficient D s for transport of SSA into water. The value of D s = 4.4 x 10-11 m 2 s-1 yielded over a range of drug loading is smaller than the load-dependent values obtained when allowance is not made for dimensional changes. The procedure has also been used to determine the diffusion coefficient for water into polymer.
Hemijska industrija, 2012
The aim of this paper is to propose equations for the diffusion of drugs for investigated drug/hydrogel systems using the parameters affecting the transport of drug through poly-(2-hydroxyethylmethacrylate/itaconic acid) (P(HEMA/IA)), poly(2-hydroxyethylacrylate/itaconic acid) (P(HEA/IA)), and poly(2-hydroxyethylmethacrylate/poly(alkyleneglycol) (meth)acrylates) (P(HEMA/BIS)) copolymeric hydrogels. Different monomer types, as well as the variable content of some components in hydrogel composition (the amount of ionizable comonomer (IA) and different type of nonionic poly(alkyleneglycol) (meth)acrylates), ultimately defined the pore size available for drug diffusion. The hydrogels synthesized ranged from nonporous to microporous, based on the classification in accordance to the pore size, and could be classified as hydrogels that contain ionic groups and hydrogels without ionic groups. The drugs selected for this study are bronchodilators-theophylline (TPH), fenethylline hydrochloride (FE), and antibiotic cephalexin (CEX). Results of in vitro drug release tests defined the release systems based on the drug type, as well as the type of hydrogel used. The diffusion coefficient of drugs and the restriction coefficient, λ, defined as the ratio of solute to "pore" radius (r s /r ζ ) that describes the ease of drug release from the gels, were used as factors that govern the release process.