• Design & Manufacturing
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• v.18 no.3
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• pp.1-8
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• 2024

Macular degeneration is a disease that damages the macula, the center of the retina, and is one of the three major eye diseases along with glaucoma and diabetic retinopathy. The optic nerve and most of the photoreceptor cells are located here, and since this is where images of objects are formed, it is the most important area for vision. The main symptom of macular degeneration is the inability to clearly distinguish the shape of objects or the inability to distinguish colors and light and dark. It is also a serious eye disease that causes black spots in the center of the field of vision. However, it is difficult to distinguish it from the form of vision loss due to presbyopia, so early diagnosis is often missed. The most common treatment for macular degeneration is antibody injection therapy. This treatment requires regular injections once every 1-2 months. When receiving antibody injection therapy, the fear of having to inject directly into the eye and the cost of long-term repeated procedures are a great burden to patients. To overcome these problems, special sustained-release formulations using drug delivery systems are being developed. Since the release speed and release time of the drug can be controlled, the number of times the drug is administered can be drastically reduced. However, the implant (Ø 0.46×6.0mm), which is a sustained-release agent, is manufactured by mixing biodegradable resin (PLGA) and therapeutic agent in a ratio of 4:6, so it is very brittle and there is a high risk of implant damage during handling. In order to safely insert the implant into the eye, a transport device that can be driven with controlled force is required. Therefore, in this study, the lever operating force was measured and analyzed to determine the influence of factors according to the cross-sectional thickness and shape of the linkage produced through injection molding as well as the post-process.

• Journal of Pharmaceutical Investigation
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• v.34 no.5
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• pp.401-406
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• 2004

To develop an intravenous delivery system of all-trans retinoic acid (ATRA) for the cancer therapy, poly(L-lactic acid) nanoparticles were prepared and characterized. Emulsification-solvent evaporation method was chosen to prepare submicron sized nanoparticles. Spherical nanoparticles less than 200 nm in diameter with narrow size distribution were prepared, and the entrapment efficiency of drug was more than 95%. The endothermic peak at $183^{\circ}C$ and X-ray crystallographic peak of ATRA appeared in the nanoparticle system, suggesting the inhibition of crystallization of ATRA by polymer adsorption during the precipitation process. ATRA was released at $37^{\circ}C$ for 60 days and the release rate was dependent on the concentration of drug incorporated in the nanoparticles. While ATRA was unstable in the light, it was very stable at $4^{\circ}C$. These results suggest the usefulness of PLA nanoparticles as a sustained and prolonged release carrier for ATRA.

• Journal of Pharmaceutical Investigation
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• v.36 no.4
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• pp.245-251
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• 2006

The novel microsphere blending and multiple emulsion method by single process was tried to prepare sustained release microspheres which release a physiologically active substance for long periods of time. A drug was separately dissolved in each of two or more oils containing biodegradable polymers to give the primary oil phases. The primary oil phases were dispersed in single aqueous phase in succession. From the drug-dispersed solution, the organic solvent was removed to produce microspheres. The accelerated drug release from the microsphere formulation prepared by single process through the multiple emulsion method was very similar to a physical blending of separately prepared microspheres using the same polymers. But long term release was not same. In this study, leuprorelin acetate loaded poly(lactide-co-glycolide) microsphere formulation for one-month delivery was developed by the multi-emulsion method followed by solvent extraction/evaporation method.

• Macromolecular Research
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• v.15 no.7
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• pp.623-632
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• 2007

Thermosensitive nanoparticles were prepared via the self-assembly of two different $poly({\varepsilon}-caprolactone)$-based block copolymers of poly(N-isopropylacrylamide)-b-$poly({\varepsilon}-caprolactone)$ (PNPCL) and poly(ethylene glycol)-b-$poly({\varepsilon}-caprolactone)$ (PEGCL). The self-aggregation and thermosensitive behaviors of the mixed nanoparticles were investigated using $^1H-NMR$, turbidimetry, differential scanning microcalorimetry (micro-DSC), dynamic light scattering (DLS), and fluorescence spectroscopy. The copolymer mixtures (mixed nanoparticles, M1-M5, with different PNPCL content) formed nano-sized self-aggregates in an aqueous environment via the intra- and/or intermolecular association of hydrophobic PCL chains. The microscopic investigation of the mixed nanoparticles showed that the critical aggregation concentration (cac), the partition equilibrium constants $(K_v)$ of pyrene, and the aggregation number of PCL chains per one hydrophobic microdomain varied in accordance with the compositions of the mixed nanoparticles. Furthermore, the PNPCL harboring mixed nanoparticles evidenced phase transition behavior, originated by coil to the globule transition of PNiPAAm block upon heating, thereby resulting in the turbidity change, endothermic heat exchange, and particle size reduction upon heating. The drug release tests showed that the formation of the thermosensitive hydrogel layer enhanced the sustained drug release patterns by functioning as an additional diffusion barrier.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.43 no.2
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• pp.165-174
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• 2017

This study reports a synthesis of an amphiphilic linear block copolymer consisting of a hydrophobic poly (lactide) (PLA) block and a hydrophilic hyperbranched polyglycerol (hbPG) block, PLA-b-hbPG. Simple chemical modification of the hbPG block with 4-hydroxycinnamic acid (CA) led to a photo-crosslinkable block copolymer, PLA-b-hbPG-CA. Nanosized micelles of the block copolyemrs were used as drug carriers for sustainable release. The hbPG shell made of a small molecular weight hbPG block showed excellent hydrophilicity, which can minimize in vivo toxicity. The UV-crosslinked PLA-b-hbPG-CA micelles loaded with drugs colud be served as a drug delivery carrier for its biocompatibility and self-assembled structures.

• Journal of Pharmaceutical Investigation
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• v.37 no.3
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• pp.193-196
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• 2007

This study aimed to evaluate and develop $Eudragit^{(R)}$-coated pellets based on the dissolution using the paddle method. As coating materials, two types of $Eudragit^{(R)}$ were applied to obtain either sustained release form or fast released form. The dissolution test was carried out in phosphate buffer solution (pH 6.5) at $37^{\circ}C$, 100 rpm. In order to develop a sustained release preparation containing felodipine, a comparative dissolution study was done using commercial product as a control. The dissolution at 30 min of felodipine from $Eudragit^{(R)}$ RS or RL-coated pellets were 0.96% and 99.65, respectively. The weight ratio of $Eudragit^{(R)}$ RL pellets to RS pellets altered the dissolution rate, but did not optimize the dissolution rate. However, the sustained dissolution of felodipine from pellets was optimized by varying the coating ratios of $Eudragit^{(R)}$ RS. It is suggested that the coating ratio of pellets is the main factor which controls dissolution rate. Taken together, $Eudragit^{(R)}$ RS 30D-coated pellets showed the most comparable dissolution rate pattern to commercial product, $Splendil^{(R)}$. This sustained release pellets for oral delivery system of felodipine was simply manufactured, and drug release behavior was highly reproducible.

• Journal of Pharmaceutical Investigation
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• v.32 no.3
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• pp.185-190
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• 2002

To improve the solubility of poorly water-soluble drug and to develop a sustained release tablets, the need for the technique, the formation of solid dispersion with polymeric materials that can potentially enhance the dissolution rate and extent of drug absorption was considered in this study. The 1:1, 1:4, and 1:5 solid dispersions were prepared by spray drying method using PVP K30, ethanol and methylene chloride. The dissolution test was carried out at in phosphate buffer solution at $37^{\circ}C$ in 100 rpm. Solid dispersed drugs were examined using differential scanning calorimetry and scanning electron microscopy, wherein it was found that felodipine is amorphous in the PVP K30 solid dispersion. Felodifine SR tablets were prepared by direct compressing the powder mixture composed of solid dispersed felodipine, lactose, Eudragit and magnesium stearate using a single punch press. In order to develop a sustained-release preparation containing solid dispersed felodipine, a comparative dissolution study was done using commercially existing product as control. The dissolution rate of intact felodipine, solid dispersed felodipine and its physical mixture, respectively, were compared by the dissolution rates for 30 minutes. The dissolution rates of felodipine for 30 minutes from 1:1, 1:4, 1:5 PVP K30 solid dispersion were 70%, 78% and 90%. However, dissolution rate offelodipine from the physical mixture was 5% of drug for 30 minutes. Our developed product Felodipine SR Tablet showed dissolution of 17%, 50% and 89% for 1, 4, and 7 hours. This designed oral delivery system is easy to manufacture, and drug releases behavior is highly reproducible and offers advantages over the existing commercial product. The dissolution rate of felodipine was significantly enhanced, following the formation of solid dispersion. The solid dispersion technique with water-soluble polymer could be used to develop a solid dispersed felodipine SR tablet.

• KSBB Journal
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• v.11 no.6
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• pp.676-680
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• 1996

The characteristics of controlled drug release were studied for a biodegradable drug delivery system. A biodegradable chitosan matrix was prepared after swelling chitosan with 10%-acetic acid and adding sulfadiazine. The release behavior of sulfadiazine from the chitosan matrix was studied using the Higuchi's diffusion controlled model in phosphate buffer solutions of pH 7.4 and pH 1.2. The drug release time was delayed by increasing the content of sulfadiazine. The drug release at pH 7.4 was more delayed than that at pH 1.2. The reason is that chitosan has greater swelling abilities at low pH than at high pH. The apparent release rate constant(K) increased as the concentration of drug increased. In shoat, the formulation the biodegradable chitosan matrix to suppress the burst effect of drug release mechanism, which led to a sustained release pattern.

• Journal of Pharmaceutical Investigation
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• v.36 no.2
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• pp.109-114
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• 2006

Biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles were developed for sustained delivery of water-soluble macromolecules. PLGA nanoparticles were fabricated by spontaneous emulsification solvent diffusion method generating negatively charged particles and heterogeneous size distribution. As a model drug, blue dextran was encapsulated in PLGA nanoparticles. In addition, nanoparticles were also prepared with varying ratio of poloxamer 188 (P188) and poloxamer 407 (P407), and coating with poly(vinyl alcohol) (PVA). Then, the particle size, zeta potential and encapsulation efficiency of nanoparticles containing blue dextran were studied. In vitro release of blue dextran from nanoparticles was also investigated. The surface and morphology of nanoparticles were characterized by scanning electron microscopy (SEM). In case of nanoparticles prepared with PLGA, P407, and different organic solvents, particle size was in the range of $230{\sim}320\;nm$ and zeta potentials of nanoparticles were negative. The SEM images showed that ethyl acetate is suitable for the formulation of PLGA nanoparticles with good appearance. Moreover, ethyl acetate showed higher encapsulation efficiency than other solvents. The addition of P188 to formulation did not affect the particle size of PLGA nanoparticles but altered the release patterns of blue dextran from nanoparticles. However, PVA, as a coating material, altered the particle size with increasing the PVA concentration. The nanoparticles were physically stable in the change of particle size during long-term storage. From the results, the PLGA nanoparticles prepared with various contents of poloxamers and PVA, could modulate the particles size of nanoparticles, in vitro release pattern, and encapsulation of water-soluble macromolecules.

• Journal of Pharmaceutical Investigation
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• v.31 no.2
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• pp.101-106
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• 2001

Alginate-chitosan (anion-cationic polymeric complex) was prepared to control the release rate of silver sulfadiazine (AgSD). Na-alginate (2%) solution containing AgSD was gelled in $CaCl_2$ solution. The gel beads formed were immediately encapsulated with chitosan (CS). The gel matrix and membrane were then reinforced with chondroitin-6-sulfate (Ch6S). Release rate of AgSD from the gel matrix was investigated by placing alginate beads in the sac of cellulose membrane simmered in HEPES-buffer solution. The concentration of AgSD released was analyzed by UV at 264 nm. Incorporation capacity of AgSD in Ca-alginate gel was more than 90%. Alginate-Ch6S-CS could control the release rate of AgSD. The amount of AgSD release was dependent on the AgSD loading dose. Incorporation of tripolyphosphate (polyanionic crosslinker) onto the alginate-Ch6S-CS bead increased the release rate of AgSD. Collagen-coating had no influence on the AgSD release rate. Alginate-Ch6S-CS beads with a sufficiently high AgSD encapsulation were capable of controlling the release of the drug over 10 days. In summary, alginate-Ch6S-CS beads could be used as a sustained delivery for AgSD and provide local targeting with low silver toxicity and patient discomfort.