• Journal of Pharmaceutical Investigation
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• v.26 no.2
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• pp.119-124
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• 1996

To develop oral controlled release dosage forms, ionic interactions between polymers and drugs were evaluated. Hydroxypropylmethyl cellulose and carboxymethylene were used as model nonionic and ionic polymers, respectively. 5-fluorouracil, propranolol-HCl and sodium salicylate were selected as model nonionic, cationic and anionic, respectively. Polymer-drug mixtures were compressed into tablets and drug release kinetics from these tablets were determined. Drug release from the tablets made of the nonionic polymer was not affected by the charge of drugs, rather, was regulated by the solubility of drugs in different pH releasing media. However, drug release kinetics were significantly affected when drug-polymer ionic interactions exist. Enhanced drug release was observed from anionic drug-anionic polymer tablets due to ionic repulsion, whereas drug release was retarded in cationic drug-anionic polymer tablets owing to ionic attractive force. Therefore, the results suggested that the polymer-drug interactions are important factors in designing controlled release dosage forms.

• Journal of Pharmaceutical Investigation
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• v.19 no.4
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• pp.179-183
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• 1989

Drug release experiments were performed based on pH-sensitive swelling behaviors of polymethacrylic acid. 5-Fluorouracil as a nonionic model drug revealed release patterns depending solely on pH-dependent swelling kinetics of polymethacrylic acid. In contrast, release of propranolol hydrochloride as a cationic model drug was significantly affected by ionic drug-polymer interaction as well as the swelling kinetics. Accordingly, a zero-order release pattern was obtained at pH 7, which was distinguished from the general matrix type drug release pattern.

• Biotechnology and Bioprocess Engineering:BBE
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• v.6 no.5
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• pp.326-331
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• 2001

With the aim of developing of pH-sensitive controlled drug release system, a poly(Llysine) (PLL) based cationic semi-interpenetrating polymer network (semi-IPN) has been synthesized. This cationic hydrogel was designed to swell at lower pH and de-swell at higher pH and therefore be applicable for achieving regulated drug release at a specific pH range. In addition to the pH sensitivity, this hydrogel was anticipated to interact with an ionic drug, providing another means to regulate the release rate of ionic drugs. This semi-IPN hydrogel was prepared using a free-radical polymerization method and by crosslinking of the polyethylene glycol (PEG)-methacrylate polymer through the PLL network. The two polymers were penetrated with each other via interpolymer complexation to yield the semi-IPN structures. The PLL hydrogel thus prepared showed dynamic swelling/de-swelling behavior in response to pH change, and such a behavior was influenced by both the concentrations of PLL and PEG-methacrylate. Drug release from this semi-IPN hydrogel was also investigated using a model protein drug, streptokinase. Streptokinase release was found to be dependent on its ionic interaction with the PLL backbones as well as on the swelling of the semi-IPN hydrogel. These results suggest that a PLL semi-IPN hydrogel could potentially be used as a drug delivery platform to modulate drug release by pH-sensitivity and ionic interaction.

• YAKHAK HOEJI
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• v.41 no.1
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• pp.22-29
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• 1997

Poloxamer-poly (acrylic acid) (PAA) interpenetrating polymer networks (IPNs) were prepared via matrix polymerization of acrylic acid with poloxamer prepolymer. The equilibrium s welling of poloxamer/PAA IPNs was determined in various pH medium. The swelling of poloxamer/PAA IPNs was more affected by pH difference compared with the swelling of homo PAA gel due to protonation and deprotonation of the PAA network, followed by reversible formation and dissociation of the interpolymer complex due to hydrogen bonding between acidic hydrogens and ether oxygens. Nonionic/anionic/cationic drugs were incorporated into IPN matriceds as a model drug and their release behavior was studied. Nonionic, drug revealed release patterns depending solely on pH dependent swelling kinetics. In contrast, the release of ionic drugs was significantly affected by ionic drug-polymer interaction as well as the swelling kinetics.

• Journal of Pharmaceutical Investigation
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• v.21 no.3
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• pp.149-153
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• 1991

Polyethylene oxide (PEO)-polymethacrylic acid (PMAA) interpenetrating polymer networks (IPN) were synthesized via radical polymerization of PMAA and simultaneous crosslinking of PEO using triisocyanate. The equilibrium swelling of PEO-PMAA IPN was determined at different pHs. The swelling of PEO-PMAA IPN, ranged from 20% to 90%, was more sensitive than that of homo polymer PMAA gel This is probably due to protonation and deprotonation of the PMAA network and interpolymer complex formation between PEO and PMAA. Several model drugs were loaded into the IPN matrices and the release mechanisms were investigated. The release of nonionizable drugs such as ftorafur and prednisolone was controlled by swelling of the matrices. However, he release of propranolol, positively charged drug, was more affected by the ionic interaction between the drug and PMAA newtork, and the interpolymer complexation.

• Journal of Biomedical Engineering Research
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• v.9 no.1
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• pp.73-78
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• 1988

The polymer electrolyte complex hydrogels consisting of poly (methacrylic acid) and poly (4-vinylpyrridine) were formed and 5-flurouracil and pilocarpine drugs were loaded on their hydrogels. Cumulative 5-FU released from PEC hydrogel was affected by the degree of loading and release rate of 5-FU was followed by the monolithic type. Cumulative pilocarpine released from PEC hydrogel increased by ionic interaction between cationic pilocarpine and anionic PMA. Release rate showed the zero order after burst effect.

• Journal of Pharmaceutical Investigation
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• v.32 no.4
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• pp.327-330
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• 2002

Alginate based polymeric matrices were designed for controlled release and stabilization of cefaclor in gastrointestinal fluid. Cefaclor is known to be acid stable and subjected to be degraded at neutral and alkaline pHs. In order to achieve an effective release profile of cefaclor in gastrointestinal tract, a particular strategy in dosage form design should be required from the view point of maintaining its activity. The amphiphilic nature of cefaclor allowed its controlled release using ionic polymers based on ionic interaction between the drug and polymers. The thrust of this study was to develop a technique that delivers cefaclor keeping effective release rate in the intestinal tract. Considering the fast degradation of cefaclor in the intestinal fluid, the matrices were designed to release surplus amount of cefaclor. The alginate based matrices demonstrated increase in release rate in the simulated intestinal fluid, which was favorable to compensate the degraded portion of cefaclor. In addition, stabilization of cefaclor in the intestinal fluid was obtained by employing citric acid that provides an local acidic environment. The matrices might be valuably used for the development of an oral cefaclor dosage form.