• Biomaterials and Biomechanics in Bioengineering
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• v.1 no.1
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• pp.13-25
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• 2014

In the current study, a drug-eluting stent coated with biodegradable polymers and sirolimus was developed by using an ultrasonic nanocoater and characterized in aspects of surface smoothness and coating thickness. In addition, in vitro release profiles of sirolimus by changing top coating layer with different biodegradable polymers were investigated. Smooth surfaces with variable thickness could be fabricated by optimizing polymer concentration, flow rate, nozzle-tip distance, gas pressure, various solvents and ultrasonic power. Smooth surface could be generated by using volatile solvents (acetone, chloroform, and methylene chloride) or post-treating with solvent vapor. Coating thickness could be controlled by varying injection volume or polymer concentration, and higher concentration could reduce the coating time while obtaining the same thickness. The thickness measurement was the most effectively performed by a conventional cutting method among three different methods that were investigated in this study. Release profiles of sirolimus were effectively controlled by changing polymers for top layer. PLGA made the release rate 3 times faster than PDLLA and PLLA and all top layers prevented burst release at the initial phase of profiles. Our results will provide useful and informative knowledge for developing drug-eluting stents, especially coated with biodegradable polymers.

• Journal of Pharmaceutical Investigation
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• v.41 no.4
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• pp.217-225
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• 2011

The aim of this work was to prepare porous osmotic pump tablets for controlled delivery of Aceclofenac. Aceclofenac solid dispersion was prepared to improve the solubility by using the drug - carrier (Mannitol) ratio of 1:1. The osmotic pump tablets were prepared using the solid dispersed product of Aceclofenac. The formulation contains potassium chloride as osmotic agent, cellulose acetate as semipermeable membrane, poly ethylene glycol (PEG 4000) as pore former and sodium lauryl sulphate (SLS) as solubility enhancer. The formulations were designed by the general factors such as osmotic agent and pore former. All formulations were evaluated for various physical parameters and, the in vitro release studies were conducted as per USP. The drug release kinetic studies such as zero order, first order, and Higuchi and Korsmeyer peppas were determined and compared. All the formulations gave more controlled release compared to the marketed tablet studied. Numerical optimization techniques were applied to found out the best formulation by considering the parameter of in vitro drug release kinetics and dissolution profile standards. It was concluded that the porous osmotic pump tablets (F7) composed of Aceclofenac solid dispersion/Potassium chloride/Lactose/Sodium lauryl sulphate/Magnesium Stearate (400/40/95/10/5, mg/tab) and coating composition with Cellulose acetate/ PEG 4000 (60/40 %w/w) is the most satisfactory formulation. The porous osmotic pump tablets provide prolonged, controlled, and gastrointestinal environment-independent drug release.

• Journal of Pharmaceutical Investigation
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• v.35 no.6
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• pp.445-451
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• 2005

As a selective ${\alpha}_{1A}-adrenoreceptor$ antagonist, tamsulosin has been used clinically for urinary obstructed patients with benign prostatic hyperplasia. The single and multi-layered pellets containing tamsulosin hydrochloride were prepared in an effort to control the drug release, avoiding dose-dependent side effects of tamsulosin hydrochloride upon oral administration. The drug release from multi-layered pellets was substantially controlled, compared with single layered pellets. The drug release from coated pellets with single or multi layer was affected by the nature of coating agent, the percentage of coating level and the presence of hydrophilic material in coating layer. In conclusion, the controlled release oral delivery system using multi-layered pellet is very useful for tamsulosin hydrochloride, resulting in improvement of patient compliance and therapeutic drug levels for a longer period of time.

• Polymer(Korea)
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• v.31 no.4
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• pp.329-334
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• 2007

Osmotic pellet system, which is one of the oral drug delivery systems, has been developed to improve manufacturing process, reduce product cost and other problems of osmotic tablet systems. Osmotic pellet is consisted of water swellable seed layer, drug layer, and membrane layer. Among them, the membrane layer plays an important role in a control of the drug release. In this work, we examined the effect of ratio for Eudragit RL and RS on the drug release behavior. Osmotic pellet with nifedipine as a model drug was easily obtained in a good yield by fluidized bed coater. Osmotic pellet showed round morphology with a range of size $1300{\sim}1500\;{\mu}m$. In the experiment of nifedipine release, the release amount increased with the increase of the ratio of Eudragit. This is due to the fact that Eudragit RL contains more hydrophilic quaternary ammonium group than Eudragit RS. Additionally, the release amount was retarded with increasing the membrane thickness. There are no differences in the release amount measured at the different pH 1.2, 6.5, 6.8, and 7.2. In conclusion, it was found that the drug release from osmotic pellets depended on the composition ratio and coating thickness of membrane layer.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.16 no.11
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• pp.7549-7554
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• 2015

The aim of this study was to develop gastric retentive bi-layered tablet using floating drug delivery technique. Metformin was selected as a model drug due to its narrow absorption window as well as very highly water solubility. These properties of metformin led to be difficult controlling the drug release. The bi-layered tablet was prepared with bi-layered compression machine to minimize interference between floating part and controlling part. The tablet weight, appearance and hardness were evaluated after compression process. The times of 'time to floating' and 'Floating duration' were tested for floating ability and drug release study was also carried out to understand drug release behavior. Furthermore, the drug release of bi-layered tablet was compared with marketed metformin tablet with sustained release pattern (Glucopharge XR$^{(R)}$).The floating ability and drug release behaviors were well controlled by changing amounts of $NaHCO_3$ (floating substance) and hydroxypropyl methylcellulose (HPMC; release control material). Bi-layered tablet had 13s of time to float, over 10h of floating duration and very similar drug release behavior compared with Glucopharge XR$^{(R)}$($f_2$: 89.6). Consequently, the bi-layered tablet with floating ability was successfully prepared and these properties can maximize the efficacy of metformin.

• Korean Journal of Clinical Pharmacy
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• v.1 no.1
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• pp.23-30
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• 1991

The sustained-release beads containing terbutaline sulfate (TBS) were prepared by rotogranulation method. The drug was dusted on the non-pareil seeds in a CF-granulator. The sustained-release beads were obtained by coating the active beads with ethylcellulose or $Eudragits^{(R)}$, using in any case the same granulator employed for active beads preparation. The release characteristics of sustained-release beads were examined in vitro by rotating basket method applied to $Bricanyl^{(R)}$ durules which is a sustained-release TBS matrix tablet. The release of terbutaline from the beads in vitro was first-order, and the release rate was dependent on both the coat weight ratio and membrane hydrophilicity. Both surfaces of the beads before and after dissolution were smooth. The drug release pattern from the beads could be thought the diffusion through the polymer membrane. The release rate and the surface of the beads stored for 3 years at room temperature were the same with those of the initial beads.

• Macromolecular Research
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• v.17 no.9
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• pp.709-713
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• 2009

The aim of this study was to develop novel intestinal specific drug delivery systems with pH sensitive swelling and drug release properties. The carboxyl group of ibuprofen was converted to a vinyl ester group by reacting ibuprofen and vinyl acetate as an acylating agent in the presence of catalyst. The glucose-6-acrylate-1, 2, 3, 4-tetraacetate (GATA) monomer was prepared under mild conditions. Cubane-1, 4-dicarboxylic acid (CDA) linked to two 2-hydroxyethyl methacrylate (HEMA) group was used as the crosslinking agent (CA). Methacrylic-type polymeric prodrugs were synthesized by the free radical copolymerization of methacrylic acid, vinyl ester derivative of ibuprofen (VIP) and GATA in the presence of cubane cross linking agent. The structure of VIP was characterized and confirmed by FTIR, $^1H$ NMR and $^{13}C$ NMR spectroscopy. The composition of the cross-linked three-dimensional polymers was determined by FTIR spectroscopy. The hydrolysis of drug polymer conjugates was carried out in cel-lophane membrane dialysis bags, and the in vitro release profiles were established separately in enzyme-free simulated gastric and intestinal fluids (SGF, pH 1 and SIF, pH 7.4). The detection of a hydrolysis solution by UV spectroscopy at selected intervals showed that the drug can be released by hydrolysis of the ester bond between the drug and polymer backbone at a low rate. Drug release studies showed that increasing the MAA content in the copolymer enhances the rate of hydrolysis in SIP. These results suggest that these polymeric prodrugs can be useful for the release of ibuprofen in controlled release systems.

• Bulletin of the Korean Chemical Society
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• v.35 no.5
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• pp.1333-1336
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• 2014

Expanded polytetrafluoroethylene (ePTFE) grafts have been used as vascular access for many patients suffering from end stage renal disease. However, the vascular graft can cause significant clinical problems such as stenosis or thrombosis. For this reason, many studies have been performed to make drug eluting graft, but initial burst is major problem in almost drug eluting systems. Therefore we used biodegradable polymer to reduce initial burst and make sustained drug delivery. The ePTFE grafts were dipped into a paclitaxel-dissolved solution and then PLGA-dissolved solution was passed through the lumen of ePTFE. We analyzed whether the dose of paclitaxel is enough and the loading amount of PLGA on ePTFE graft increases according to the coating solution's concentration. Scanning electron microscope (SEM) images of various concentration of PLGA showed that the porous surface of graft was more packed with PLGA by tetrahydrofuran solution dissolved PLGA. In addition, in vitro release profiles of Ptx-PLGA graft demonstrated that early burst was gradually decreased as increasing the concentration of PLGA. These results suggest that PLGA coating of Ptx loaded graft can retard drug release, it is useful tool to control drug release of medical devices.

• Journal of Pharmaceutical Investigation
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• v.41 no.6
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• pp.347-354
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• 2011

Repeated oral administration of loxoprofen can induce many side effects such as gastric disturbances and acidosis. Therefore, we considered alternative routes of administration for loxoprofen to avoid such adverse effects. The aim of this study was to develop an ethylene-vinyl acetate (EVA) matrix system containing a permeation enhancer for enhanced transdermal delivery of loxoprofen. The EVA matrix containing loxoprofen was fabricated and the effects of drug concentration, temperature, enhancer and plasticizer on drug release were studied from the loxoprofen-EVA matrix. The solubility of loxoprofen was highest at 40% (v/v) PEG 400. The release rate of drug from drug-EVA matrix increased with increased loading dose and temperature. The release rate was proportional to the square root of loading dose. The activation energy (Ea), which was measured from the slope of log P versus 1000/T, was 5.67 kcal/mol for a 2.0% loaded drug dose from the EVA matrix. Among the plasticizer used, diethyl phthalate showed the highest release rate of loxoprofen. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the greatest enhancing effect. In conclusion, for the enhanced controlled transdermal delivery of loxoprofen, the application of the EVA matrix containing plasticizer and penetration enhancer could be useful in the development of a controlled drug delivery system.

• Journal of Microbiology and Biotechnology
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• v.9 no.1
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• pp.50-55
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• 1999

To develop a new form of controlled release dosage for administering for indomethacin (IND), two formulations of IND-loaded nanoparticles were designed based on polysaccharide (guar) derivatives. Nanoparticles prepared by the dialysis method were characterized with respect to morphology, size distribution, drug content, and in vitro drug release. Morphological studies by scanning electron microscopy (SEM) indicated that guar acetate (GA) nanoparticles were spherical in shape and had a smooth surface. The particle size distributions of formulation I (40mg of GA) and formulation II (80mg of GA) were shown to be $250.78\pm185.13nm$ and $718\pm145.90nm$ in distilled water ($20$^{\circ}C$), respectively. The drug loading efficiencies of nanoparticles were approximately 26% and 31% for formulations I and II, respectively. The differential scanning calorimetry (DSC) results indicated that the IND was perfectly distributed within GA nanoparticles. We also found, from the X-ray diffractometry analysis, that a decrease in the degree of crystallinity of the drug occurred in the nanoparticles. No changes between the original IND and the released IND from GA nanoparticles were detected by FT-IR. Using guar acetate, it is possible to design nanoparticles which allow the controlled release of IND over an extended period of time.