• Journal of Pharmaceutical Investigation
• /
• 제26권2호
• /
• pp.119-124
• /
• 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
• /
• 제19권4호
• /
• pp.179-183
• /
• 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.

• 한국고분자학회:학술대회논문집
• /
• 한국고분자학회 2006년도 IUPAC International Symposium on Advanced Polymers for Emerging Technologies
• /
• pp.180-180
• /
• 2006

A novel preparation method for core/shell nanoparticles with protein drug-loaded lipid core was designed and characterized. The lipid core is composed of lecithin and protein drug and the polymeric shell is composed of Pluronics (poly (ethylene oxide)-poly (propylene oxide)-poly(ethylene oxide) triblock copolymer, F-127 For the application of core/shell nanoparticles as a protein drug carrier, lysozyme and Vascular Endothelial Growth Factor (VEGF) were loaded into the core/shell nanoparticles by electrostatic interaction and the drug release pattern was observed by manipulating the polymeric shell.

• Biotechnology and Bioprocess Engineering:BBE
• /
• 제6권5호
• /
• pp.326-331
• /
• 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.

• Macromolecular Research
• /
• 제15권6호
• /
• pp.547-552
• /
• 2007

Water soluble polymer, poly(vinyl pyrrolidone) was chosen to conjugate with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(succinyl) (N-succinyl DPPE) to make a new drug delivery system. PVP with an amine group (amino-PVP) was polymerized by free radical polymerization. The amine group of amino-PVP was conjugated with the carboxylic group of N-succinyl DPPE. The resultant conjugate could form nanoparticles in the aqueous solution; these nanoparticles were termed a lipid-polymer system. The critical aggregation concentration was measured with pyrene to give a value of $1{\times}10^{-3}g/L$. The particle size of the lipid-polymer system, as measured by DLS, AFM and TEM, was about 70 nm. Lipophilic component in the inner part of the lipid-polymer system could derive the physical interaction with hydrophobic drugs. Griseofulvin was used as a model drug in this study. The loading efficiency and release profile of the drug were measured by HPLC. The loading efficiency was about 54%. The release behavior was sustained for a prolonged time of 12 days. The proposed lipid-polymer system with biodegradable and biocompatible properties has promising potential as a passive-targeting drug delivery carrier because of its small particle size.

• Journal of Pharmaceutical Investigation
• /
• 제41권1호
• /
• pp.45-50
• /
• 2011

Nonclassical pathway of crystallization has been utilized to modify the properties and morphologies of inorganic and organic/inorganic materials. In here, the polymer-directed crystallization method has been applied to the pharmaceutical active ingredient to assess the applicability for as a particle engineering tool. The polymer-directed crystallization was successful to modifying the crystal size, habit and morphology, but it was not effective to discover the novel polymorphs of Sibutramine (SB). SB was selected as a model drug and polyacrylic acid (PAA), polyethylene imine (PEI) and chitosan (CHI) were added as a crystallization pathway modifier. SB was crystallized via drowning crystallization using methanol or ethanol as a solvent and water as a non-solvent. The significant interactions between polymer and the drug were confirmed by measuring the solubility of the drug in presence of polymer during the crystallization. The crystal forms of SB are characterized by X-ray diffraction (XRD), scanning electron microscope (SEM) and optical microscope (OM). The polymer-directed crystallization seems to be able to modify the crystal properties of pharmaceutical active ingredient, which is critical in determining the bioavailability, processability, and stability.

• Journal of Pharmaceutical Investigation
• /
• 제21권3호
• /
• pp.149-153
• /
• 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.

• 약학회지
• /
• 제41권1호
• /
• pp.22-29
• /
• 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
• /
• 제24권4호
• /
• pp.257-263
• /
• 1994

The interpenetrating polymer networks (IPNs) of polyacrylic acid (PAA)-polyethylene glycol (PEG) were synthesized via crosslinking of PEG and simultaneous free radical polymerization of PAA. The equilibrium swelling of the IPNs matrices, ranged from 40% to 95%, was varied to a great extent as compared with PAA homopolymer due to the interpolymer interaction between PAA and PEG. The drug release kinetics of drug loaded matrices was significantly affected by the charge of drugs as well as interpolymer complexation.

• Journal of Pharmaceutical Investigation
• /
• 제38권2호
• /
• pp.111-117
• /
• 2008

To overcome the solubility of poorly water-soluble drug, the formation of solid dispersion using a spray-dryer with polymeric material, that can potentially enhance the dissolution rate extend of drug absorption was considered in this study. $Eudragit^{(R)}$ E100 as carrier for solid dispersion is acrylate copolymer that soluble in acidic buffer solutions (below pH 5.0). It was used to increase dissolution of atorvastatin calcium as a water-insoluble drug in acidic environments. In this study, a spray-dryer was used to prepare solid dispersion of atorvastatin calcium and $Eudragit^{(R)}$ E100 for purpose of improving the solubility of drug. Atorvastatin calcium and $Eudragit^{(R)}$ E100 were dissolved in ethanol and spray-dryed. DSC and XRD were used to analyze the crystallinity of the sample. It was found that atorvastatin calcium is amorphous in the $Eudragit^{(R)}$ E100 solid dispersion. FT-IR was used to analyze the salt formation by interaction between atorvastatin calcium and $Eudragit^{(R)}$ E100. Comparative dissolution study exhibited better dissolution characteristics than the commercial drug ($Lipitor^{(R)}$) as control. The dissolution rate of atorvastatin calcium was markedly increased in solid dispersion system in simulated gastric juice (pH 1.2). This study proposed that this solid dispersion system improved the bioavailability of poorly water-soluble atorvastatin calcium.