• 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.

• Journal of Pharmaceutical Investigation
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• v.35 no.6
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• pp.453-460
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• 2005

4-Aminopyridine (AP) is a potassium channel blocker used in the treatment of neurological disorders such as multiple sclerosis and Alzheimer disease. AP‘s window of therapeutic effect appears to correlate with its plasma halflife (3.5 hours). It demonstrates pH-dependent solubility because of a weakly basic drug. In addition, the resulting release from conventional matrix tablets decreases with increasing pH-milieu of the gastrointestinal tract. The aim of this study is to design sustained release matrix tablet containing AP, overcoming this problem. $Eudragit^{\circledR}$ L 100 (EuL) and sodium alginate were used in an effort to achieve pH independent drug release. The effect of sodium alginate and EuL on drug release from matrix tablet was investigated. The drug release behavior from the different tablets was analyzed by $t_{20%},\;t_{40%},\;t_{60%}$, The exponential diffusion coefficient n, kinetic constant K were calculated according to the Korsmeyer-Peppas equation. The drug release from matrix tablets prepared with sodium alginate was decreased with increasing the content of sodium alginate in pH 7.4 while there is no significant difference in pH 1.2. The exponent n values were determined to be approximately 0.5 and 0.8 respectively, in both pH 1.2 and 7.4. These values indicate diffusion-based anomalous mechanism and erosion-based anomalous mechanism, respectively. The drug release from sodium alginate matrix tablets prepared with solid dispersion of EuL containing drug showed a slow drug release in an acidic medium and a more fast drug release in phosphate medium, compared with sodium alginate matrix tablets prepared with physical mixture. These results may be attributed to the gel forming ability of sodium alginate and pH dependent solubility of EuL. Therefore, sustained-release AP matrix tablets using sodium alginate and EuL were successfully prepared.

• Carbon letters
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• v.10 no.3
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• pp.208-212
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• 2009

Alginate-chitosan blend containing coconut-based activated carbon was prepared as a drug delivery carrier in order to improve the loading and releasing capacity of the drug. The activated carbon was incorporated as effective adsorbent for drug due to the extremely high surface area and pore volume, high adsorption capacity, micro porous structure and specific surface activity. Alginate-chitosan blend containing coconut-based activated carbon showed the sustained release for a longer period. Alginate-chitosan blend showed higher release of drug as the pH increased and higher release of drug as the content of chitosan decreased due to the pH-dependent solubility of blend components.

• Journal of Pharmaceutical Investigation
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• v.24 no.3
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• pp.139-144
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• 1994

The effect of some formulation variables on the release rate of famotidine, a $H_2$ receptor antagonist, from cellulose matrices containing hydroxypropylcellulose (HPC) in different ratios and types was investigated. The effects of tablet shape and compression pressure on dissolution rate of famotidine were studied. And the effect of the pH of dissolution media was also studied. Increase in the ratio of polymer to drug decreased the release rate of famotidine. Increase of the polymer viscosity also decreased the release rate. The release rate of famotidine was dependent on the pH of dissolution media. The release rate of drug was not much dependent on the compression pressure but dependent on the tablet shape and/or surface area. Consequently, the release rate of famotidine can be modified by changing the HPC contents, types of polymers with different viscosity grades or using appropriate fillers.

• 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.

• 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.

• Archives of Pharmacal Research
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• v.12 no.2
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• pp.88-93
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• 1989

In order to obtain some informations about the effect of molecular weight on the release rate of drug from drug carrier, two types of poly-L-glutamic acid (PLGA)-cytarabine (ara-C) conjugates, PLGA-ara-C:I and PLGA-ara-C:II, were synthesized using two types of PLGA having different average molecular weight, 43,000 and 77,800, respectively. The PLGA-ara-C conjugates were synthesized by mixed anhydride method and found to be covalently linked. Both types of conjugates charged negatively at biological pH. The pH-dependent release rate of ara-C was observed in both cases, and the release rate was accelerated in basic, acidic conditions (the k values were 0.015 $day^{-1}$ at pH 7.0, 0.024 $day^{-1}$ at pH 5.0, and 0.059 $day^{-1}$ at pH 9.0 in the case of PLGA-ara-C:I) and in the presence of pretense. The time required for the release of 16.5% of ara-C from PLGA-ara-C:I were 8 hr and 144 hr in the presence and absence of protease, respectively. Although both types of conjugates showed similar drug substitution ratio, they showed different release rates. Between the two types of conjugates, PLGA-ara-C:II showed the faster release rate (0.030 vs 0.042 $day^{-1}$ in pH 7.4 phosphate buffer solution at $37^{\circ}C$) and the smaller activation energy for the release of drug (12.5 vs 7.7 Kcal/mol) than PLGA-ara-C:I. The characteristic effect of molecular weight on the release rates of PLGA-ara-C conjugates suggests that the drug release rate might be effectively controlled over a prolonged period of time by the combined use of the different types of PLGA-ara-C conjugates having different molecular weights.

• Archives of Pharmacal Research
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• v.28 no.8
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• pp.983-987
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• 2005

Hydrogels composed of glycidyl methacrylate dextran (GMD) and poly(acrylic acid, PM) were prepared by UV irradiation method for colon-specific drug delivery. GMD was synthesized by coupling of glycidyl methacrylate to dextran in the presence of 4-(N,N-dimethylamino)pyridine. GMD was photo-polymerized by ammonium peroxydisulfate as initiating system in phosphate­buffered solution (0.1 M, pH 7.4). And then, acrylic acid monomer was added and subsequently heat-polymerized by 2,2'-azobisisobutyronitrile as an initiator. The hydrogels exhibited high swelling ratio (about 20) at $37^{\circ}C$, and showed a pH-dependent swelling behavior. In addition, the swelling ratio of the hydrogel was remarkably enhanced to about 45 times in the presence of dextranase at pH 7.4. The swelling-deswelling behavior proceeded reversibly for the GMD/PM hydrogels between pH 2 and pH 7.4. Release of 5-aminosalicylic acid from the GMD/PAA hydrogels was evaluated in simulated gastrointestinal pH fluids in the absence or presence of dextranase. We concluded that the hydrogels prepared could be used as a dual-sensitive drug carrier for sequential release in gastrointestinal tract.

• Journal of Pharmaceutical Investigation
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• v.19 no.3
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• pp.145-154
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• 1989

Methyl methacrylate-butyl methacrylate copolymer (MMBM)-povidone (PVP) films were investigated as a potential topical drug delivery system for the controlled release of econazole nitrate as a model drug. The effect of changes in film composition, drug concentration, film thickness, pH and temperature of release medium on the in vitro release of econazole nitrate were studied. The release rate constant was found to be increased with increasing povidone content in dry films. Drug release followed zero-order kinetics in the initial stage and then release rate increased gradually with time, espicially in the films having larger proportions of PVP. The release rate was found to be dependent on drug content, film thickness, the pH and temperature of release medium. Antimicrobial test showed that microbial growth was inhibited markedly with increasing proportions of PVP in films. Also drug content and film thickness affected the antimicrobial activity.

• Journal of Pharmaceutical Investigation
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• v.23 no.4
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• pp.213-216
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• 1993

${\kappa}-Carrageenan$, an anionic polysaccharide, was employed in tablet formulations and its function as a drug release sustaining agent was investigated. Tablets composed of ${\kappa}-carrageenan$ and hydroxypropyl methylcellulose were fabricated by using direct compression method. Lactose and sodium alginate were utilized as controls for ${\kappa}-carrageenan$. Drug release experiments performed at pHs 1.2 and 7.4 revealed that ${\kappa}-carrageenan$ retains pH-dependent sustained release effects due to its anionic characteristics. Also, the ionic interaction between ${\kappa}-carrageenan$ and drugs exerted significant affects on drug release kinetics. ${\kappa}-Carrageenan$ was found out to be a useful additive for sustained release tablet formulations.