• Archives of Pharmacal Research
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• v.15 no.2
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• pp.162-168
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• 1992

Release characteristics of five different types of hydrophilic albumin microspheres (HAM) containing different ratios of methotrexate-albumin (MTX-HSA) conjugates to free MTX: 1 : 0 (HAMC), 3 :1 (HAMC 3F), 1 :1 (HAMCF), 1:3 (HAMCF3) and 0 : 1 (HAMF) were investigated in the absence or presence of protease using dissolution tester. In all the HAMs studied except HAMC, the MTX was released bi-exponentially in the absence of protease; an initial fast release period up to approximately 6h, and thereafter the release rate was very much slower. The fast release of MTX from the HAMs (such as HAMC3F, HAMCF, HAMCF3 and HAMF) at the initial phase in probably due to the release of "physically associated" MTX from the core of the HAMs. The initial rate constants were 7.2, 8.7, 8.5 and 5.9 times greater than the second rate constants for HAMF, HAMCF3, HAMCF and HAMC3F, respectively. MTX release from HAMC was very slow and mono-phasic. It was at most 2.2% of the total entrapped amount by 24 h. The protease accelerated the release of MTX from the HAMs. The percentages of MTX released from HAMs up to 24 h were 100, 89.0, 75.0, 66.0 and 61.0% for HAMF, HAMCF3, HAMCF, HAMC3F and HAMC, respectively in the presence of protease and the corresponding values in the absence of protease were 30.2 19.0, 10.0, 6.5 and 2.2%, respectively. In vitro release of MTX in the presence of protease varied according to the ratios of MTX-HSA conjugates to MTX; the data set from HAMF, HAMCF3 and HAMCF fits better to monophasic first-order profile more adequately than to zero-order profile, that of HAMC3 monophasic first-order, and that of HAMC to bi-phasic zero-order. Above results suggested that zero-order release rate can be achieved by adjusting the ratio of MTX-HSA conjugates to MTX in the preparation of HAMs such as HAMC3F.as HAMC3F.

• Journal of Pharmaceutical Investigation
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• v.29 no.4
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• pp.343-348
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• 1999

The purpose of this study is to prepare the controlled release adhesive patch containing naproxen. Pressuresensitive adhesive (PSA)-type patch was fabricated by casting of polyisobutylene (PIE.) and mineral oil in toluene. Membrane-controlled release (MCR)-type patch was prepared by the attachment of the controlled release membrane on the PSAtype patch. The membrane was mainly composed of Eudragit, polyethylene glycol(PEG) and glycerin. The drug release profile and skin permeation test with various patches were evaluated in vitro. The release of naproxen from PIE-based PSAtype patch with various loading doses fitted Higuchi's diffusion equation. However, the permeation of naproxen through hairless mouse skin from PSA-type patch followed zero-order kinetics. In MCR-type patch, thickness of controlled release membrane affected on the drug release rate highly. In the composition of membrane, the release rate was decreased as the ratio of Eudragit increased. The drug release from the MCR-type patch followed zero order kinetics. The permeation of naproxen through hairless mouse skin from MCR-type patch showed lag time for the intial release period and didn't fit the zero-order kinetics

• Journal of Pharmaceutical Investigation
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• v.21 no.1
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• pp.1-10
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• 1991

Hydrogels containing ketoprofen were prepared by adding NaOH or $Ca(OH)_2$ solution to Eudragit L, S and Eudispert hv at various concentration. And xerogels were prepared by drying hydrogels. On the other hand, organogels containing ketoprofen were prepared by mixing Eudragit L or S and propylene glycol. Effects of polymer content and base on drug release were investigated using KP V dissolution method. The release rate of ketoprofen from Eudragit L & S hydrogel decreased with increasing in polymer content. And the drug release rate from cal. hydroxide based gels were more decreased than that from sod. hydroxide based gels. At pH 7.2 dissolution medium, e release of ketoprofen from Edispert hv hydrogel followed apparent zero order kinetics. The release of ketoprofen from xerogel involved in simultaneous absorption of water and desorption of ketoprofen via a pH-dependant swelling controlled mechanism. The release of ketoprofen from Eudragit S organogels followed apparent zero order kinetics, providing strong evidence for a surface erosion mechanism.

• Journal of Pharmaceutical Investigation
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• v.23 no.4
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• pp.207-211
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• 1993

Reservoir type devices were designed for long-term implantable drug delivery system. The reservoir type device was prepared with the polymethacrylic acid gel coated with polyurethane membrane. Release controlling agent (RCA) were employed to control drug release from devices via generation of micropores in the membranes. The polyurethane membrane functioned as a rate controlling barrier. The drug release pattern of hydrogel demonstrated zero order kinetics. The release rate of drugs could be regulated by varying hydrophobicity/hydrophilicity and content of the RCA, as well as the thickness of the polyurethane membrane. The release of drugs from this system was governed by pore mechanism via simple diffusion and osmotic pressure.

• Archives of Pharmacal Research
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• v.8 no.1
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• pp.7-14
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• 1985

Membrane-coated tablet of isonicotinic acid hydrazide (INAH) which releases INAH at the zero-order kinetics was deveoped. It consisted of a soluble tablet core surrounded by a porous membrane which controls the diffusion rate. Tablet cores were prepared by compressing granules of INAH and polyvinyl chloride (PVC) dissolved in methyl ethyl ketone in which micronized sucrose were suspended. Diffusion rate of INAH from the tablet through the membrane was constant until the loaded INAH in the core was almost released. The rate was independent of pH of the dissolution medium. Water-soluble sucrose particles behaved as a poreproducing material in the water-insoluble PVC film coat. The pH independency of the rate was probably due to the high solubility of INAH in the water of wide pH range. The diffusion rate of INAH could be controlled by chnaging the composition of the membrane or the coat weight. This membrane-coated INAH tablet seemed to be a powerful candidate for the controlled release drug delivery system (DDS) of INAH or other highly watersoluble drugs.

• 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.

• Archives of Pharmacal Research
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• v.13 no.2
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• pp.151-160
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• 1990

In order to develop a controlled-release oral drug delivery system (DDS) which sustains the plasma acetaminophen (AAP) concentration for a certain period of time, microporous membrane-coated tablets were prepared and evaluated in vitro. Firstly, highly water-soluble core tablet of AAP were prepared with various formulations by wet granulation and compression technique. Then the core tablets were coated with polyvinychloride (PVC) in which micronized sucrose particles were dispersed. Effect of formula compositions of core tablets and coating suspensions on the pharmaceutical characteristics such as drug release kinetics and membrane stability of the coated tablets was investigated in vitro. AAP was released from the coated tablets as a zero-order rate in a pH-independent manner. This independency of AAP release to pH change from 1.2 to 7.2 is favorable for the controlled oral drug delivery, since it will produce a constant drug release in the stomach and intestine regardless of the pH change in the GI tract. Drug release could be extended upto 10 h according to the coating condition. The release rate could be controlled by changing the formula compositions of the core tablets and coating suspensions, coat weight per each tablet, and especially PVC/sucrose ratio and particle size of the sucrose in the coating suspension. The coated tablets prepared in this study had a fairly good pharmaceutical characteristics in vitro, however, overall evaluation of the coated tablet should await in vivo absorption study in man.

• Journal of Pharmaceutical Investigation
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• v.22 no.3
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• pp.205-210
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• 1992

In order to develop a controlled-release oral drug delivery system (DDS) of theophylline (TP), microporous membrane-coated tablets were prepared and evaluated in vitro and in vivo. Rapidly water-soluble core tablets of TP (300 mg) were prepared by wet granulation and compression technique, Then the core tablets were spray-coated with polyvinylchloride (PVC) in which micronized sucrose particles were dispersed. Effect of formula compositions of coating suspensions on the pharmaceutical characteristics such as membrane strength and dissolution was investigated in vitro. The membranes remained unbroken in pH 1.2 buffer at $37^{\circ}C$ at least for 2 hours after the disintergration test. TP was released from the coated-released tablets at a zero-order rate over 8 hours. The release at pH 1.2 and 4.0 was similar in rate but a little more rapid than that at pH 6.8. The coated tablets were administered to three healthy male volunteers and their saliva profiles of TP were compared with those from the commercial sustained release TP tablets such as Slobid and Asconthin. Saliva TP concentrations from the coated tablets were successfully sustained over 48 hours after the dosing and were comparable to those of the commercial sustained-release tablets. The membrane-coating technique is very simple and does not need any sophisticated equipments. In this respect, the membrane-coated tablets may be superior to the commercial sustained-release tablets and this technique is worth adopting by the pharmaceutical industries.

• Polymer(Korea)
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• v.25 no.3
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• pp.334-342
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• 2001

Gentamicin sulfate (GS)-loaded poly(3-hydroxybutyrate-co-3-hydroxyvalerate)(PHBV) devices were prepared for controlled-release of antibiotics. In this study, the effects of thickness, hydroxyvalerate (HV) content, initial drug-loading ratio, and additive content on the release profile have been investigated. The morphology of devices was examined with scanning electron microscope (SEM) before and after in vitro release; their highly porous surface and cross-sectional were observed. It could be suggested that device would be affected by the packing of the HV and additive content, which would depend on their structure. A high performance liquid chromatography (HPLC) was used to detect and quantify the release of GS from the device. The drug release from all the devices showed biphasic release patterns, and some matrices released the incorporated antibiotic throughout 30 days with a near zero-order release rate. The release patterns were shown to be changed by altering the thickness, copolymer ratio, and additive content.

• 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.