• Archives of Pharmacal Research
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• v.12 no.3
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• pp.191-195
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• 1989

The release of progesterone from monolithic devices composed of different ratios of polyethylene oxide (PEO; mw 20, 000) and hydrophobic polydimethylsiloxane was investigated. Water soluble PEO soaked into the polymer provided controlled release of progesterone. The release rate of progesterone could be controlled by varying the contents of PEO and progesterone in soaking solution. The progesterone release rate from silicone devices increased as the content of PEO in devices increased, while it decreased as the content of PEO in soaking solution increased. The release rate may be made by simple alterations of geometry of devices controlled swelling and the change in the physical structure of polymer network. Hydrophobic polydimethylsiloxane containing PEO and progesterone can provide a contraceptive material for prolonged release of progesterone.

• Journal of Biomedical Engineering Research
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• v.28 no.4
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• pp.484-493
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• 2007

Two polymeric prodrugs of PGE1 (prodrugs IVg and PNg) were newly synthesized. The drug conjugation proceeded in quantitative yield without decomposition of PGE1 to PGA1. With two types conjugates, PEG-PGE1 and PN-PGE1 with different spacer groups, we first discovered a possibility of slow release of PGE1 in blood circulatory system. PGE1 is conjugated with PEG and PN through the long alkylene spacers, and their availability as polymeric prodrugs is evaluated. Their drug-releasing behavior was examined both in phosphate buffer (pH=7.4) and rat plasma. Each prodrug was known to be highly stabile in the buffer solution. The drug-releasing rate became much faster in rat plasma than in the buffer solution due to the acceleration by the plasma enzymes. The drug-release was found to reach a plateau in rat plasma because the released PGE1 or its derivatives may be captured or decomposed by the plasma proteins. The slower drug-releasing rate of pro drug PNg in rat plasma is reasonably attributed to the molecular aggregation due to the hydrophobic bonding between the PGE1 moieties and spacers.

• Archives of Pharmacal Research
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• v.23 no.4
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• pp.367-373
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• 2000

Cholic acid, conjugated with amine-terminated poly(W-isopropylacrylamide) (abbreviated as CA/ATPNIPAAm), was synthesized by a N, N'-dicyclohexyl carbodiimide (DCC)-mediated coupling reaction. Self-assembled CA/ATPNIPAAm micelles were prepared by a diafiltration method in aqueous media. The CA/ATPNIPAAm micelles exhibited a lower critical solution temperature (LCST) at $31.5^{\circ}C$. Micelle sizes measured by photon correlation spectroscopy (PCS) were approximately 31.6 $\times$$\times$ 5.8 nm. The CA/ATPNIPAAm micelles were spherical and their thermal size transition was observed by transmission electron microscope (TEM). A fluorescence probe technique was used for determining the micelle formation behavior of CA/ATPNIPAAm in aqueous solutions using Pyrene as a hydrophobic Probe. The critical micelle concentration (CMC) was evaluated as $8.9{\times}0^{-2}$ g/L. A drug release study was performed using indomethacin (IN) as a hydrophobic model drug. The release kinetics of IN from the CA/ATPNIPAAm micelles revealed a thermo-sensitivity by the unique character of poly(N-isopropylacrylamide) i.e. the release rate was higher at $25^{\circ}C$ than at $37^{\circ}C$.

• Journal of Pharmaceutical Investigation
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• v.26 no.4
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• pp.299-308
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• 1996

In order to develop the controlled release of a drug from the suppsitories, in vitro drug release and in vivo absorption in rabbits were investigated. Various suppository forms with hollow cavities, into which drugs in the form of fine powder or solid dispersion system(SDS) could be placed, were utilized. The polyvinyl alcohol(PVA) hydrogel as a base, and propranolol HCl(PPH) as a model drug were employed. In vitro drug dissolution studies showed that the dissolved amounts(%) of PPH from PPH-methylcellulose(MC)-SDS and PPH-ethylcellulose(EC)-SDS reached 100% and 63% in 4.5-hours, respectively. In the relative strength test for PVA hydrogel, PVA hydrogel became harder and more rigid when the number of freezing-thawing cycles and the ratio of PVA 2000 were increased. In vitro drug release profile revealed that the release rate(%) of PPH from PPH-EC-SDS and PPH-MC-SDS hollow type suppositories were sustained. The release amount(%) of PPH from PPH-EC-SDS hollow type suppositories was not affected by storage time, but since the use of hydrophilic MC made PPH diffuse into the hydrogel after it absorbed the water of base, the various release patterns were appeared as the storage time went by. In vivo absorption experiments with rabbits showed that PPH-EC-SDS(PPH : EC=1:3) hollow type suppository delayed the absorption of PPH, significantly. The $C_{max}$, $AUC_{0{\rightarrow}8}$ and MRT of PPH powder hollow type suppository were $196.37{\pm}5.63\;ng/ml$, 1105.26 ng/ml/min and 8.66 min, respectively. The $C_{max}$, $AUC_{0{\rightarrow}8}$ and MRT of PPH-EC-SDS(PPH : EC=1:3) were $91.30{\pm]14.14\;ng/ml$, 554.69 ng/ml/min, 235.99 min, respectively.

• Polymer(Korea)
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• v.27 no.5
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• pp.449-457
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• 2003

The purposes of this work were the producing of a biodegradable poly($\varepsilon$-caprolactone) (PCL) / poly(ethylene oxide) (PEO) microcapsule and the analyzing of form and features for the manufacturing conditions which could be observed in a prospective drug delivery systems through drug release. The effects of emulsifier, emulsifier concentration, and stirring rate for the diameter and form of the microcapsules were observed using image analyzer and scanning electron microscope. The role of interfacial adhesion between PCL/PEO and drug was determined by contact angle measurements, and the drug release test of the microcapsules was characterized by UV/vis. spectra. As a result, the microcapsules were made in spherical fonns with a mean particle size of 170 nm∼68 $\mu$m. And the work of adhesion between water and PCL/PEO increased with increasing the content of PEO, probably due to the increased the hydrophilicity. It was also found that the drug release rate from the microcapsules significantly increased with increasing the content of PEO, which could be also attributed to the increasing of the hydrophilic groups or the degree of adhesion force at interfaces.

• 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.

• Journal of Biomedical Engineering Research
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• v.8 no.2
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• pp.135-144
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• 1987

Polyamide microcapsules were designed for a sustained drug release. As a model, riboflavin was e no apsulated in polyamide microcapsules. Polyamide microcapsules were prepared from thiamines and acid bichlorides by the interfacial polycondensation reaction. The diamines used in ttlis works were ethylenediamine and 1, 6-hexamethylenediamine. Sebacoylchloride and teruphthaloylchloride were employed as acid bichlorides. The following parameters were studied; the release of several kinds of polyamide microcapsules , the various concentrations of diamines and acid dichlorides ; the various concentrations of surfactants : the various pH range of sink solution during the dissolution test. The release amount of riboflavin from aromatic polyamide micrcapsule was higher than that of aliphatic polyamide microcapsule The release rate of riboflavin from the polyamide microcapsule was decreased with increase of concentration of thiamines, arid dichlorides and surfactants which is used for preparing polyamide microcapsule. Release riboflavin from polyamide microcapsule was lower at pH 7 than pH 2 in sink-solution for dissolution test.

• Journal of Pharmaceutical Investigation
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• v.19 no.4
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• pp.195-202
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• 1989

In attempt to improve the chemotherapeutic activity of adriamycin, adriamycin-entrapped HSA microspheres were prepared and investigated by the various in vitro experiments. The shape, surface characteristics and size distribution of HSA microspheres are observed by scanning electron microscopy. The in vitro drug release, albumin matrix degradation by protease of HSA microspheres were studied. The shape of HSA microspheres were spherical and the surface was smooth and compact. The size of HSA microspheres ranged from 0.4 to $2.5\;{\mu}m$ and have average diameters of 0.5 to $0.7\;{\mu}m$. The size distribution of HSA microspheres prepared by ultrasonication was mainly affected by albumin concentration and heating time in the process of hardening. In in vitro, almost all adriamycin was released from HSA microspheres for 8 hr. Analysis of the resulting adriamycin release profiles demonstrated that adriamycin is released from the microspheres in two distinct steps, a fast phase (until 30 min) followed by a much slower sustained release phase. Drug release, which is due to diffusion, was depended on the rate of matrix hydration. Drug release was largely affected by albumin concentration and heating temperature during the process of hardening. Albumin matrix degradation of HSA microspheres was affected by heating temperature and albumin concentration. Higher temperature and longer times generally produce harder, less porous, and slowly degradable microspheres.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.282-282
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• 1996

The purpose of this study was to prepare the nifedipine dry elixir (NDE) and coated nifedipine dry elixir (CNDE) containing nifedipine ethanol solution for improving the dissolution rate and bioavailability of nifedipine. NDE containing nifedipine and ethanol in wall materials of dextrin was prepared using a spray-dryer and then NDE was coated with eudragit acrylic resin to make CNDE. Shape and size of the NDE and CNDE were monitored by scanning electron micrograph and laser particle size analyzer In vitro dissolution tests were performed in simulated gastric and intestinal fluid. Bioavailability of NDE and CNDE were compared with drug powder suspension and commercial soft capsule after oral administration of the preparations to rats. NDE and CNDE are spherical in shape. Cross-sectional view of dry elixirs indicates the large inter cavity containing ethanolic drug solution in shell. Geometric mean diameter of NDE and CNDE is about 6.64 and 8.70 $\mu\textrm{m}$, respectively. Drug dissolution rate within first 5 min from NDE increased dramatically irrespective of dissolution medium. However, CNDE showed a particularly retarded dissolution rate in pH 1.2 simulated gastric fluid compared with NDE. The bioavailability of nifedipine in the NDE was increased dramatically compared with drug powder suspension. CNDE reduced initial burst-out plasma peak compared with NDE. CNDE as a sustained release delivery system could reduce the initial burst-out plasma peak due to controlling the release rate of nifedipine from NDE and maintain the effective plasma level over a longer period within therapeutic window with enhanced bioavailability of nifedipine.

• Journal of Pharmaceutical Investigation
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• v.25 no.2
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• pp.153-161
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• 1995

Alginic acid is a hydrophilic , colloidal polysaccharide obtained from cell wall of seaweed or brown algae and has a broad range of applications. Alginlc acid becomes alginate gel bead due to its cation-induced gelation. Dried alginate beads can be reswollen according to environmental pH. The purpose of this paper is to explore the possible applicability of alginate beads as an oral controlled release system of ibuprofen. In this experiment ibuprofen was incorporated in alginate beads and alginate beads were treated with various methods. Ibuprofen release from alginate beads in phosphate buffer (pH 7.4) was laster than in distilled water and dilute HCl. The release of ibuprofen was more sustained in bead than simple mixture and coprecipitate of ibuprofen and sodium alginate. The dissolution rate of ibuprofen was decreased in using of bead that hardened with formaldehyde. The dissolution rate of the drug from the bead was the fastest in 12 hour dried beads, 1.5%-sodium alginate concentration and 1%-calcium chloride concentration. Sodium alginate bead can be used as a sustaind release drug delivery system of water-insoluble drugs.