• Journal of Pharmaceutical Investigation
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• 제30권3호
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• pp.207-211
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• 2000

The objective of this work is to investigate the effect of molecular weight of poly(ethylene oxide) (PEO) and release medium on the release of nifedipine (NP) from PEO tablets containing NP and to get some mechanistic insights into the release of NP. The tablets containing NP were prepared by direct compression, using a flat-faced punch and die. The molecular weights of PEOs used were 200K, 900K, 2000K and 7,000K. The release kinetics were studied for 24 hours in aqueous ethanol solution, using a dissolution tester at $36.5^{\circ}C$ and 100 rpm. Drug release rate increased, as the concentration of ethanol in the dissolution medium increased, due to the increased solubility of NP. As the molecular weight of PEO increased, release rate decreased, due to the slower swelling and dissolution of PEO. The power values obtained by fitting data to the power law expression $(M_t/M_{\infty}=kt^n)$ indicated that, at low ethanol concentration, the release of NP is governed by anomalous diffusion. However, as the ethanol concentration increases, diffusional release becomes to prevail over anomalous or zero-order release. Overall, these results provided some insights into the release of NP from PEO tablet.

• Journal of Pharmaceutical Investigation
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• 제32권3호
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• pp.199-207
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• 2002

In order to develop a sustained release formulation of bovine somatotropin (BST), which has been used to increase the body weight of oxen or the milk production of dairy cows, poly(D,L-lactide-co-glyceride)(PLGA) microspheres were made by W/O/W multiple emulsification method and solvent extraction method. Physical properties including particle size, drug entrapment, drug release, protein denaturation, and in vivo body weight increase in rats were characterized. The size of the microspheres was increased as the molecular weight of PLGA increased. When Span 65 and stearic acid during preparation were added, the size was decreased but the amount of surface protein was increased, resulting in a high loading efficiency, with fast release of BST from the microspheres. Aggregation or fragmentation of BST by SDS-PAGE during microsphere preparation and drug release study was not observed. Body weight of Sprague-Dawley's male rats was significantly increased after subcutaneous administrations of BST-loaded PLGA microspheres. There was a good correlation between in vivo weight gain and in vitro release rate of microspheres. PLGA microspheres with a high surface protein ratio could be a good candidate for the sustained delivery of BST.

• Journal of Pharmaceutical Investigation
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• 제28권4호
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• pp.275-282
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• 1998

In order to develop a desirable in vitro release which correlates well with in vivo bioavailability, hollow type suppository containing Propranolol HCl(PPH) powder in the cavity and conventional type suppository with dispersed PPH in the base were prepared. Polyvinyl alcohol (PVA) hydrogel as a base and PPH as a model drug were used for the preparation of suppository. The rates of drug release from the suppositories were studied by Paddle method, Muranish method, Dialysis tubing method and Rotating dialysis cell method. The release profiles from suppositories using the four different release tests were compared. After a rectal administration in rat, the mean $C_{max}$ of hollow type suppository was significantly lower than that of conventional type, but $T_{max}$, $AUC_{0{\to}12}$ and MRT of hollow type were significantly higher 1.6 times, 1.2 times and 1.9 times than those of conventional type, respectively. The computer program was used to simulate plasma concentration from in vitro released amounts of drug and in vivo pharmacokinetic parameters. Based on comparison of the simulated bioavailability from computer program with experimental bioavailability in rat we have found out in vitro release test which correlates well with in vivo bioavailability. Our results have shown the best correlation between in vitro release and in vivo bioavailability in PPH-PVA hydrogel hollow type suppository for the paddle method and conventional type suppository for the rotating dialysis cell method. In this work we propose that PPH-PVA hydrogel suppository shows in vitro-in vivo correlation. This data should help to optimize the formulation of the drug and provide a basis for quality control procedures.

• Archives of Pharmacal Research
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• 제26권1호
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• pp.34-39
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• 2003

The traditional Asian medicinal herb, roots of Astragalus (A.) membranaceus (Leguminosae), is used for many purposes, some of which are purported to stimulate the release of growth hormone in vivo. Extracts of A. membranaceus were tested to determine whether they stimulate the release of growth hormone in rat pituitary cell culture. A. membranaceus was extracted sequentially with 80% ethanol (fraction A), n-hexane (fraction B); the test compound from the herbal extraction was isolated using silica gel column chromatography and was identified with spectral data. Test compound was also extracted by traditional boiling water methods. Induction of growth hormone in pituitary cell culture was conducted with isolated compounds and extracted fractions of A. Radix (dried roots of A. membranaceus). The fraction A was not active in the rat pituitary cell culture, but the fraction B derived from the ethanol fraction stimulated the release of growth hormone in culture. Six compounds from fraction B (1-6) were isolated and identified previously. The compounds 1,2-benzendicarboxylic acid diisononylester (1), $\beta$-sitosterol (2), and 3-Ο-$\beta$-D-galactopyranosyl-$\beta$-sitosterol (5) did not induce growth hormone release in the culture. Formononetin (3), 9Z, 12Z-octadecadienoic acid (4), stigmast-4-en-6$\beta$-o1-3-one (6) and 98-E, a mixture of 1'-9, 12-octadecadienoic acid (Z,Z)-2',3'-dihydroxy-propylester (7) and 1'-hexadecanoic acid-2',3'-dihydroxy-propylester (8) stimulated the release of growth hormone in the rat pituitary cell culture significantly compared to the control. In conclusions, four compounds isolated from extracts of A. Radix induced growth hormone release in the rat pituitary cell culture. The 98-E isolate was the most active inducer of growth hormone release.

• Archives of Pharmacal Research
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• 제28권8호
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• pp.983-987
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• 2005

Hydrogels composed of glycidyl methacrylate dextran (GMD) and poly(acrylic acid, PM) were prepared by UV irradiation method for colon-specific drug delivery. GMD was synthesized by coupling of glycidyl methacrylate to dextran in the presence of 4-(N,N-dimethylamino)pyridine. GMD was photo-polymerized by ammonium peroxydisulfate as initiating system in phosphate­buffered solution (0.1 M, pH 7.4). And then, acrylic acid monomer was added and subsequently heat-polymerized by 2,2'-azobisisobutyronitrile as an initiator. The hydrogels exhibited high swelling ratio (about 20) at $37^{\circ}C$, and showed a pH-dependent swelling behavior. In addition, the swelling ratio of the hydrogel was remarkably enhanced to about 45 times in the presence of dextranase at pH 7.4. The swelling-deswelling behavior proceeded reversibly for the GMD/PM hydrogels between pH 2 and pH 7.4. Release of 5-aminosalicylic acid from the GMD/PAA hydrogels was evaluated in simulated gastrointestinal pH fluids in the absence or presence of dextranase. We concluded that the hydrogels prepared could be used as a dual-sensitive drug carrier for sequential release in gastrointestinal tract.

• Journal of Pharmaceutical Investigation
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• 제16권1호
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• pp.12-17
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• 1986

Etilefrine hydrochloride was microencapsulated with ethylcellulose by phase separation method to develop a sustained release dosage form. The results of dissolution test carried out with various microcapsules showed that the drug release was decreased with increasing the particle size of microcapsules at a constant core to wall ratio, and with decreasing the core to wall ratio. Also ethylcellulose 50 cps and fast stirring rate (900 rpm) was better in decreasing the drug release than ethylcellulose 22 cps and slow stirring rate (300 rpm), respectively.

• International Journal of Precision Engineering and Manufacturing
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• 제9권2호
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• pp.81-83
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• 2008

The Rapid Prototyping (RP) technology has advanced in many application areas. In this research, two different types, cylinder and scaffold, of implantable Drug Delivery System (DDS) were fabricated using Nano Composite Deposition System (NCDS), one of the RP systems. The anti-cancer drug (5-fluorouracil, 5-FU), biodegradable polymer (PLGA(85: 15)), and bio ceramic (Hydroxyapatite, HA) were used to form drug-polymer composite material. Both types of DDS were evaluated in vivo environment for two weeks. For evaluation, the cumulative drug release and shape stability were measured. Test results showed that the scaffold DDS provide higher cumulative drug release and has better stability than cylinder DDS.

• Macromolecular Research
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• 제11권4호
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• pp.207-223
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• 2003

For last five years, we are developing the novel local drug delivery devices using biodegradable polymers, especially polylactide (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) due to its relatively good biocompatibility, easily controlled biodegradability, good processability and only FDA approved synthetic degradable polymers. The relationship between various kinds of drug [water soluble small molecule drugs: gentamicin sulfate (GS), fentanyl citrate (FC), BCNU, azidothymidine (AZT), pamidronate (ADP), $1,25(OH)_2$ vitamin $D_3$, water insoluble small molecule drugs: fentanyl, ipriflavone (IP) and nifedipine, and water soluble large peptide molecule drug: nerve growth factor (NGF), and Japanese encephalitis virus (JEV)], different types of geometrical devices [microspheres (MSs), microcapsule, nanoparticle, wafers, pellet, beads, multiple-layered beads, implants, fiber, scaffolds, and films], and pharmacological activity are proposed and discussed for the application of pharmaceutics and tissue engineering. Also, local drug delivery devices proposed in this work are introduced in view of preparation method, drug release behavior, biocompatibility, pharmacological effect, and animal studies. In conclusion, we can control the drug release profiles varying with the preparation, formulation and geometrical parameters. Moreover, any types of drug were successfully applicable to achieve linear sustained release from short period ($1{\sim}3$ days) to long period (over 2 months). It is very important to design a suitable formulation for the wanting period of bioactive molecules loaded in biodegradable polymers for the local delivery of drug. The drug release is affected by many factors such as hydrophilicity of drug, electric charge of drug, drug loading amount, polymer molecular weight, the monomer composition, the size of implants, the applied fabrication techniques, and so on. It is well known that the commercialization of new drug needs a lot of cost of money (average: over 10 million US dollar per one drug) and time (average: above 9 years) whereas the development of DDS and high effective generic drug might be need relatively low investment with a short time period. Also, one core technology of DDS can be applicable to many drugs for the market needs. From these reasons, the DDS research on potent generic drugs might be suitable for less risk and high return.

• 약학회지
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• 제31권1호
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• pp.25-32
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• 1987

The effect of loading dose, plasticiser and PVA molecular weight on naproxen release from hydrophilic polymer matrix was examined. Hydrophilic polymer matrix was prepared with PVA and PVP by adding glycerine as plasticiser. The release of naproxen from polymer matrix was determined in phosphate buffer medium. The release rate of naproxen from the polymer matrix increased as drug loading dose and plasticiser percentage increased. Raproxen released from the polymer matrix showed the time square root kinetics. Without changing the release-pattern, the release rate of naproxen could not be changed by varying molecular weight of PVA. Linearly released time range increased as drug loading dose increased, whereas decreased as plasticiser percentage increased up to 30%.

• Journal of Pharmaceutical Investigation
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• 제24권3호spc1호
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• pp.33-39
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• 1994

We have studied the effect of loading amount and particle size on the rate of release of 5-fluorouracil (5-FU) from ethylene-vinyl acetate (EVA) matrix. Release rate increased as the loading amount and particle size increase. We also studied the effect of additives (lactose and algin) on the rate of release of 5-FU. Both algin and lactose promoted the rate of release. The ability to increase the rate is in the order of algin>lactose>5-FU. Scanning electron microscope study clearly shows that large cavities and cracks are created. The results imply that, by the proper combinations of the amount of the additive, $EVA_c$ and drug, the rate of drug release can be modulated over a wide range of values.