• 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.

• Macromolecular Research
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• v.17 no.7
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• pp.464-468
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• 2009

Gelatin nanoparticles derived from bovine or porcine have been developed as various types of drug delivery system, and they need to be cross-linked to maintain their physicochemical properties in aqueous environments. Although gelatin is a widely used material in pharmaceutical industries, the safety issue of animal-origin gelatins, such as transmissible mad cow disease and anaphylaxis, remains to be solved. The purpose of this study was to prepare type A gelatin (GA) nanoparticles by modified, two-step, desolvation method and compare the toxicity of the resulting GA nanoparticles with recombinant human gelatin (rHG) nanoparticles. The GA nanoparticles were characterized, and drug loading and release pattern were measured. FITC-BSA, a model protein, was efficiently loaded in the nanoparticles and then released in a biphasic and sustained release pattern without an initial burst. In particular, the cell viability of the GA nanoparticles was less than that of the rHG nanoparticles. This finding suggests that rHG nanoparticles should be considered as an alternative to animal-origin gelatin nanoparticles in order to minimize the safety problems.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.292.1-292.1
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• 2003

Purpose. To develop a new heterodisperse 650mg acetaminophen HPMC matrix tablet with biphasic sustained release profiles. Methods. Hydroxypropylmethylcellulose(HPMC) matrix tablets were prepared by wet-granulating drug with other excipients, followed by direct compression of the dried granule mixtures into tablet using a rotary tablet machine. (omitted)

• Macromolecular Research
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• v.11 no.4
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• pp.283-290
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• 2003

Organic drugs including aspirin, omeprazole, and naproxen with three different levels of octanol/water partition coefficient were examined for their release behavior from the amphiphilic PCL-b-PEO-b-PCL (PCEC) matrix. Scanning electron micrograph (SEM) of PCEC illustrated a well defined two-phase morphology consisted of dispersed poly(ethylene oxide) (PEO) domain and continuous polycaprolactone (PCL) phase. Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) experiments veri tied that three model drugs are dissolved as a molecular dispersion in PCEC matrix. The release of hydrophilic aspirin closely followed the water absorption profile of the matrix indicating that its major fraction is present in PEO domain. However, substantial amount of aspirin present in less hydrophilic region displayed discontinuous biphasic release pattern. In the case of omeprazole with intermediate hydrophobicity consistent release behavior was observed for a period of 24 hrs after the rapid liberation of ca. 10% of the drug presumably partitioned in PEO phase. It was ascribed to the fact that the progressive hydration of PCEC matrix gradually increased the chance of drug/water exposure to compensate the exhaustion of device. Naproxen with the highest octanol/water distribution coefficient among three model drugs exhibited a limited release of 35% for 24 hrs. Finally, hydroxypropyl methylcellulose phthalate (HPMCP)/PCEC blend matrix demonstrated an accelerated and quantitative release of hydrophobic naproxen by generating high porosity and thereby expanding polymer/water interface.

• Macromolecular Research
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• v.10 no.5
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• pp.246-252
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• 2002

In order to the development of the delivery device of long-acting local anesthetics for postoperative analgesia and control of chronic pain of cancer patient, fentnyl-loaded poly (L-lactide-co-glycolido) (PLGA, molecular weight, 5,000 g/mole; 50 : 50 mole ratio by lactide to glycolide) microspheres (FMS) were studied. FMS were prepared by an emulsion solvent-evaporation method. The influence of several preparation parameters such as initial drug loading, PLGA concentration, emulsifier concentration, oil phase volume, and fabrication temperature has been investigated on the fentanyl release profiles. Generally, the drug showed the biphasic release patterns, with an initial diffusion followed by a lag period before the onset of the degradation phase, but there was no lag time in our system. Fentanyl was slowly released from FMS over 10 days in vitro with a quasi-zero order property. The release rate increased with increasing drug loading as well as decreasing polymer concentration with relatively small initial burst effect. From the results, FMS may be a good formulation to deliver the anesthetic for the treatment of chronic pain.

• 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.

• Polymer(Korea)
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• v.25 no.6
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• pp.884-892
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• 2001

Biodegradable wafers were prepared with poly (L-lactide-co-glycolide) (50 : 50 mole ratio of lactide to glycolide, molecular weight:5000 g/mole) by direct compression method for the sustained release of nifedipine to investigate the possibility of the treatment of hypertension. PLGA wafers were prepared by altering initial drug/polymer loading ratio, wafer thickness, and hydroxypropyl methylcellulose (HPMC) content. These wafers showed new zero-order release patterns for 11 days, and various biphasic release patterns could be obtained by altering the composition of wafers such as addition of matrix binder as HPMC to the PLGA wafer to reduce release rate of initial phase. The onset of polymer mass loss only occured after 4 days and about 40% of mass loss was observed after 11 days nifedipine release. This system had advantages in terms of simplicity in design and obviousness of drug release rate and may be useful as an implantable dosage form.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.17 no.9
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• pp.228-234
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• 2016

The aim of this study was to develop pharmaceutical dosage forms with a bi-phasic drug using a double extrusion approach. Hot melt extrusion was performed using a co-rotating twin-screw extruder. The. 1st melt extrusion was performed using polymer with a relatively higher Tg, such as HPMC and the 2nd melt extrudate was obtained using the 1st extrudate and polymers with a lower Tg, such as HPMC-AS and PEO. In addition, the formulation with all the content in the same proportion as the double extudate was produced using single extrusion for comparison. Physical characterization was performed on the formulations employing differential scanning calorimetry (DSC). In vitro release tests were studied using a USP Type-I apparatus at $37{\pm}0.5^{\circ}C$ and 100 rpm. The similarity factor (f2) was also used to check the difference statistically. The DSC results indicated that the crystallinity of ibuprofen was changed to an amorphous state after extrusion in both double and single melt extrusion. Double melt extrudate with ibuprofen showed the desired release in acidic media (pH 1.2) in the first two hours and basic (pH 6.8) during six hours. Double melt extrudate with glimepiride showed faster release in 60 min of over 80%, whereas the single extrudate with glimepiride showed retarded release due to the interaction with HPMC. The similarity factor(f2) value was 28.5, which demonstrates that there were different drug release behavior between the double and single extrusion. Consequently, the double melt extrudated formulation was robust and gave the desired drug release pattern.

• Biomolecules & Therapeutics
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• v.25 no.4
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• pp.452-459
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• 2017

In this study, the effect of particle size of genistein-loaded solid lipid particulate systems on drug dissolution behavior and oral bioavailability was investigated. Genistein-loaded solid lipid microparticles and nanoparticles were prepared with glyceryl palmitostearate. Except for the particle size, other properties of genistein-loaded solid lipid microparticles and nanoparticles such as particle composition and drug loading efficiency and amount were similarly controlled to mainly evaluate the effect of different particle sizes of the solid lipid particulate systems on drug dissolution behavior and oral bioavailability. The results showed that genistein-loaded solid lipid microparticles and nanoparticles exhibited a considerably increased drug dissolution rate compared to that of genistein bulk powder and suspension. The microparticles gradually released genistein as a function of time while the nanoparticles exhibited a biphasic drug release pattern, showing an initial burst drug release, followed by a sustained release. The oral bioavailability of genistein loaded in solid lipid microparticles and nanoparticles in rats was also significantly enhanced compared to that in bulk powders and the suspension. However, the bioavailability from the microparticles increased more than that from the nanoparticles mainly because the rapid drug dissolution rate and rapid absorption of genistein because of the large surface area of the genistein-solid lipid nanoparticles cleared the drug to a greater extent than the genistein-solid lipid microparticles did. Therefore, the findings of this study suggest that controlling the particle size of solid-lipid particulate systems at a micro-scale would be a promising strategy to increase the oral bioavailability of genistein.

• Journal of Pharmaceutical Investigation
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• v.34 no.3
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• pp.185-192
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• 2004

The objective of this study was to evaluate the effects of surfactant type and concentration upon dissolution rates of carbamazepine from an immediate-release tablet. The dissolution media used in this study were aqueous solutions containing 0.1-2% sodium lauryl sulfate, cetyltrimethylammonium bromide, or polysorbate 80. The solubility of carbamazepine in the dissolution media was determined at first. A dissolution study was then conducted by using the USP dissolution apparatus II (paddle method) with an agitation rate of 75 rpm. Aliquots of the dissolution media were taken at predetermined time intervals, and the amount of carbamazepine dissolved was measured spectrophotometrically at 285 nm. The dissolution data obtained were fitted into a biphasic exponential equation with four parameters. Excellent correlations were observed between the experimental data and the theoretical ones predicted by the equation. This equation permitted the calculation of $T_{50%}$ (the time required for dissolving 50% of carbamazepine) under various experimental conditions. Differentiation of the equation also led to the attainment of dissolution rates at dissolution time points. The addition of a surfactant to an aqueous solution led to increasing the solubility of carbamazepine by 3- to 12-folds, depending upon its type and concentration. This event also resulted in enhancing the magnitude of a sink condition during the dissolution study. As a result, the dissolution rate of carbamazepine was affected by the aqueous surfactant concentration in a proportional manner. Subsequently, $T_{50%}$ values declined rapidly, as the surfactant concentration increased. Such effects were observed in decreasing order of sodium lauryl sulfate, cetyltirmethylammonium bromide, and polysorbate 80. These results clearly demonstrated that it was possible to tailor a dissolution rate and $T_{50%}$ of carbamazepine by manipulating the type and concentration of a surfactant. Relevant information would be beneficial to setting up dissolution specifications for poorly water-soluble drug products.