• Journal of Pharmaceutical Investigation
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• v.26 no.4
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• pp.263-271
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• 1996

Sulconazole nitrate(SCN), an imidazole derivative which has been effective in the treatment of dermatophytosis, tinea versicolor and candidiasis, was formulated as a gel containing drug, poloxamer 407, ethanol and propylene glycol. The resulting SCN gels were evaluated with respect to their viscosity, drug release rate, skin permeation rate. The apparent viscosity of SCN gel increased in proportion to poloxamer 407, drug and propylene glycol concentration. In case ethanol was added, the apparent viscosity decreased. The drug release rate of SCN gel increased in proportion to temperature and ethanol concentration. But the drug release rate decreased as the concentration of poloxamer 407 increased. The increase of drug concentration induced nonlinear increase of drug release rate. When propylene glycol was added at the level of 10%, the drug release rate increased but from 15% it decreased. The skin permeation rate decreased in high concentration of poloxamer 407. The skin permeation rate of SCN gel containing 15% ethanol increased about twice than that of gel without ethanol. The increase of drug concentration induced nonlinear increase of skin permeation rate. When propylene glycol was added at the level of 10%, the skin permeation rate increased but from 15% it decreased.

• Archives of Pharmacal Research
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• v.18 no.3
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• pp.183-188
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• 1995

Polymeric reinforcement and coatings of alginate beads were carried out to control the release rate of drug from alginate beads. A poorly water-soluble ibuprofen (IPF) was selected as a model drug. A commercially available $Eudragit^{\circledR}$ RS100 was also used as a polymer. Effects of polymeric contents, the presence of plasticizers and amount of drug loading on the release rate of drug were investigated. The release rate of drug from alginate beads in the simulated gastric fluid did not occur within 2 h but released immediately when dissolution media were switched to the simulated intestinal fluid. No significant difference of release rate from polymer-reinforced alginate bead without plasticizers was observed when compared to plain (simple) beads. However, the release rate of drug from polymer-reinforced alginate beads was further sustained and retarded when aluminium tristearate (AT) as a plasticizer was added to polymer. However, polyethylene glycol 400 (PEG400) did not change the release rate of drug from alginate beads although PEG400 was used to improve dispersion of polymer and sodium alginate, and plasticize $Eudragit^{\circledR}$ RS100 polymer. The presence of plasticizer was crucial to reinforce alginate gel matrices using a polymer. As the amount of drug loading increased, the release rate of drug increased as a result of decreasing effects of polymer contents in matrices. The significantly sustained release of drug from polymer-coated alginate beads occurred as the amount of polymer increased because the thickness of coated membrane increased so that cracks and pores of the outer surface of alginate beads could be reduced. The sustained and retarded action of polymer-reinforced and coated beads may result from the disturbance of swelling and erosion (disintegration) of alginate beads. From these findings, polymeric-reinforcement and coatings of alginate gel beads can provide an advanced delivery system by retarding the release rate of various drugs.

• Archives of Pharmacal Research
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• v.21 no.6
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• pp.645-650
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• 1998

The dual drug-loaded alginate beads simultaneously containing drug in inner and outer layers were prepared by dropping plain (single-layered) alginate beads into $CaCl_2$ solution. The release characteristics were evaluated in simulated gastric fluid for 2 h followed by intestinal fluids thereafter for 12 h. The surface morphology and cross section of dual drug-loaded alginate beads was also investigated using scanning electron microscope (SEM). The poorlv water-soluble ibuprofen was chosen as a model drug. The surface of single-layered and dual drug-loaded alginate beads showed very crude and roughness, showing aggregated particles, surface cracks and rough crystals. The thickness of dual drug-loaded alginate beads surrounded by outer layer was ranged from about 57 to 329mcm. The distinct chasm between inner and outer layers was also observed. In case of single-layered alginate bead, the drug was not released in gastric fluid but was largely released in intestinal fluid. However, the release rate decreased as the reinforcing $Eudragit^{\circledR}$ polymer contents increased. When the plasticizers were added into polymer, the release rate largely decreased. The release rate of dual drug-loaded alginate beads was stable in gastric fluid for 2 h but largely increased when switched in intestinal fluid. The drug linearly released for 4 h followed by another linear release thereafter, showing a distinct biphasic release characteristics. There was a difference in the release profiles between single-layered and dual drug-loaded alginate beads due to their structural shape. However, this biphasic release profiles were modified by varying formulation compositions of inner and outer layer of alginate beads. The release rate of dual drug-loaded alginate beads slightly decreased when the outer layer was reinforced with $Eudragit^{\circledR}$ RS1OO polymers. In case of dual drug-loaded alginate beads with polymer-reinforced outer layer only, the initial amount of druc released was low but the initial release rate (slope) was higher due to more swellable inner cores when compared to polymer-reinforced inner cores. The current dual drug-loaded alginate beads may be used to deliver the drugs in a time dependent manner.

• 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.

• Journal of Pharmaceutical Investigation
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• v.19 no.2
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• pp.99-107
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• 1989

In order to develop a pediatric liquid preparation with sustained release properties, dextromethorphan hydrobromide (DEXT) was complexed with strong cation exchange resin (CG 120) and the-complex was coated with Eudragit RS using a phase separation method by non-solvent addition. The effect of pH, ionic strength of the release medium and drug/resin ratio on the release rate of DEXT was studied. The release rate of free drug from the uncoated complex, and coated complexes with 9.5 and 18.5% Eudragit RS in artificial gastric juice were measured. The release rate from the uncoated complex was faster with higher pH, higher ionic strength of the release medium and higher drug/resin ratio. The release rate from the coated complex could be controlled by the amount of coating material, and the surface after release did not rupture into.

• 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.35 no.3
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• pp.157-163
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• 2005

The pellets with multiple drug release system (MDRS) of Diltiazem. HCl which consist of immediate drug release layer, drug reservoir layer and controlled release rate membrane, were prepared by using CF-Coater. As main factors for more effective MDRS of Diltiazem. HCl, ethylcellulose was used for the controlling drug release rate, and diethylphthalate was used for plasticizer, respectively. In vitro evaluation study was performed by comparative dissolution test between our test MDRS and reference Diltiazem. HCl preparation. The physical tests were performed using FT-IR and SEM. In vivo evaluation was also performed by observing the behavior of a plasma drug concentration after oral administration. The bioavailability was determined by analyzing the blood sample after oral administration to healthy, male volunteers once a day. As a result, there were no significant differences in bioequivalence parameters $(AUC_{\infty},\;C_{max},\;t_{1/2})$ between two systems. It might be concluded that our MDRS of Diltiazem. HCl could be an alternative delivery system to reference drug preparation.

• Macromolecular Research
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• v.12 no.1
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• pp.71-77
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• 2004

We have synthesized various types of poly(ethylene glycol) (PEG)-ibuprofen conjugates by nucleophilic substitution of bromo-terminated PEG with ibuprofen-Cs salt. The conversion of the terminal hydroxyl groups to bromo-termini was quantitative, as was the drug conjugation process, which suggests that the present synthetic method is very useful for the preparation of PEG-based prodrugs from pharmaceuticals having carboxyl functionalities. The drug-release behavior of the prodrugs was examined in both phosphate buffer (PBS, pH 7.4) and rat plasma. From the drug-release behavior in PBS, we determined that each prodrug has high storage stability. The drug-release rate was observed to be much faster in rat plasma than in buffer solution as a result of the acceleration effect provided by enzymes present in the plasma. The drug-release rate in rat plasma depends on the degree of molecular aggregation of the prodrugs, which can be changed effectively by the nature of their spacer groups or by the use of Pluronic as the polymer carrier.

• Journal of Pharmaceutical Investigation
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• v.21 no.4
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• pp.237-245
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• 1991

Matrix type silicone rubber devices were designed for long-term implantable drug delivery system. Release controlling agents (RCA), i.e., polypropylene glycol, polyethylene glycol, were employed to control drug release from the devices. The release rate of drug from RCA dispersed silicone matrices was mainly dependent on hydrophilicity-hydrophobicity of drug and RCA. In the case of hydrophilic drug, the release from the RCA dispersed matrix was regulated by swelling kinetics. Especially when the relatively hydrophobic polypropylene glycol was used, swelling control mechanism induced zero-order release kinetics. Whereas, the release of hydrophobic drug was resulted from partition mechanism. The effect of RCA was to increase drug diffusivity.

• Journal of Pharmaceutical Investigation
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• v.28 no.1
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• pp.51-57
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• 1998

Tetracycline lyogel ointment consisting of hydroxy ethyl cellulose(HEC) in glycerin and Eudragit RS 100 in triacetin were prepared and then release characteristic were investigated. The physical properties of lyogel ointment such as viscosity, particle size and microscopic structures were also evaluated. The microscopic structures showed that lyogel particles containing drug were dispersed in the triactin solution. The release rate of drug from lyogel ointment as a function of HEC was not changed. However the release rate was significantly decresed when the amount of Eudragit RS 100 and triacetin in lyogel ointment was increased. The viscosity and weight fraction in external phase of lyogel ointment influenced the release rate. The current studies suggest that the release rate of drug can be controlled by changing of lyogel ointment compositions.