• Macromolecular Research
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• 제16권3호
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• pp.189-193
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• 2008

Thermal cross-linking method of poly(vinyl alcohol) (PVA) using poly(acrylic acid) (PAA) was carried out on PVA/PAA hydrogels. The level of gelation was measured in the PVA/PAA hydrogels with various PAA contents. The swelling behavior at various pHs showed that the swelling kinetics and water contents of the PVA/PAA hydrogels reached equilibrium after 30 h, and the time to reach the equilibrium state decreased with increasing PAA content in the hydrogel. The water content increased with increasing pH of the buffer solution. The permeation and release of the drug were tested using indomethacin as a model drug. The permeated and released amounts of the drug increased with decreasing the PAA content because of the low free volume in the hydrogel due to the higher cross-linking density. The kinetic profile of drug release at various pHs showed that all samples reached the equilibrium state within the 5 h.

• Journal of Pharmaceutical Investigation
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• 제37권4호
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• pp.211-216
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• 2007

The bark of Alnus japonica has been used for the treatment of fever, hemorrhage and diarrehea in oriental traditional medicine. Recently, it was revealed that the diarylheptanoids from the bark of Alnus japonica possess anti-inflammatory activity and are expected to be applicable for atopic dermatitis. In this study, oregonin, one of major active components in the bark of Alnus japonica, was developed in the form of semisolid formulations for topical delivery. Oregonin was incorporated into four ointment bases: O/W cream, W/O cream, hydrophilic ointment and lipophilic ointment. Oregonin release from all formulation prepared was evaluated. Franz cell method and immersion method were employed to characterize the release patterns of drug from each formulation based on solvent availability. O/W cream showed a better release profile than the other formulations when evaluated with Franz cell method with an order of O/W cream, hydrophilic ointment, W/O cream and lipophilic ointment. In the immersion method, hydrophilic ointment showed the greatest release rate at times 1 hour exceeding compared to other bases with an order of hydrophilic ointment, O/W cream, W/O cream and lipophilic ointment. Hydrophilicity and solvent availability of formulation seems to significantly influence the release rate of oregonin from ointment bases. In this study, we successfully characterized the oregon in ointment and found that o/w cream is a promising formulation for the topical delivery of oregonin.

• Journal of Pharmaceutical Investigation
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• 제38권2호
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• pp.105-110
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• 2008

Indapamide (4-chloro-N-(2-methyl-1-indolinyl)-3-sulfamoyl-benz-amide) is an oral antihypertensive diuretic agent indicated for the treatment of hypertensive. The diuretic and natriuretic effects are mainly due to the structure of o-chlorobenzenesulfonamide. The objective of this study was to formulate sustained release indapamide granules and assess their formulation variables. Granules were prepared by fluid bed coating method and consist of drug layer and membrane layer. The granules were coated with HPC and ethyl cellulose along with plasticizer dibuthyl sebacate. The release of indapamide depended on the type of Eudragit such as RS and NE 30 D used in the formulation controlled release layer. These results obtained clearly suggest that the sustained release oral delivery system for indapamide could be designed with satisfying drug release profile approved.

• Journal of Pharmaceutical Investigation
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• 제27권4호
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• pp.323-329
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• 1997

Ipriflavone is non-hormonal antiosteoporotic drug which inhibits bone resorption by reducing recruitment and/or differentiation of osteoclasts, and stimulates proliferation and differentiation of osteoblast, and also enhances calcitonin secretion in the presence of estrogen. Although some kinds of immediately-released preparation of ipriflavone are available in commercial market, in present study, we tried to formulate sustained-release tablet using coating method with hydrophobic and hydrophilic coating materials. In vitro dissolution test was applied to evaluate sustained-release patterns of several test preparations (Test tablet A, B and C) designed using different preparation method or different compositions. From the results of dissolution test, test tablet A which showed suitable dissolution profile was selected as the candidate of new product. Pharmacokinetic evaluation of test drug, ipriflavone sustained-release tablets, was conducted in 6 beagle dogs weighing $11.5{\pm}0.5\;Kg$ compared with $Theobon^{\circledR}$ tablet, immediately-released tablet (Kukjae Pharm. Co.) as reference drug. Two products were randomly administered to 6 beagle dogs, and after 1 week, cross-over study was conducted. From the present study, AUC and $T_{max}$ of test product were significantly different from those of reference product (p<0.05), respectively$(AUC\;:\;3646.28{\pm}472.56\;vs\;3646.28{\pm}472.56\;ng{\cdot}hr/ml,\;T_{max}\;:\;4.33{\pm}1.03\;vs\;1.42{\pm}0.38\;hr)$. But $C_{max}$ was not significantly different between two products (p>0.05) $(\;512.52{\pm}48.18\;vs\;443.97{\pm}140.53\;ng/ml)$. From the results of pharmacokinetic evaluations, it was noted that absorption amount of test product was increased, but absorption rate was delayed and $C_{max}$ of two products were not changed. And it was concluded that redesign of the sustained-release preparation which has a lower content of iprifavone rather than test tablet A must be considered.

• Journal of Pharmaceutical Investigation
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• 제32권2호
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• pp.103-106
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• 2002

A method that describes the determination of the in vitro release of ketoprofen from gels was suggested. The experimental system of the method consists of a Franz diffusion cell, which contains a pH 7.4 phosphate buffer as a receptor medium, and a $70\;{\mu}m$ mesh woven nylon membrane as a diffusion barrier. Under the given condition of the system, the diffusion of ketoprofen across the membrane was rapid enough that the apparent release profile of ketoprofen obtained from the present method could represent the release of the drug from gel preparations. The release of ketoprofen in the present method was reproducible, and the rate increased in proportion to the concentration of ketoprofen in the gel. These suggest that the present method is applicable to the quality evaluation of gel preparations containing ketoprofen.

• Bulletin of the Korean Chemical Society
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• 제32권3호
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• pp.867-872
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• 2011

For the prolonged delivery and sustained release rates of low molecular weight drugs, poly(lactic-co-glycolic acid) (PLGA) microparticles containing the drug SKL-2020 have been investigated. On increasing polyvinyl alcohol (PVA) concentration (from 0.2% to 5%), the size of microparticles decreased (from $48.02{\mu}m$ to $10.63{\mu}m$) and more uniform size distribution was noticeable due to the powerful emulsifying ability of PVA. A higher drug loading (from 5% to 20%) caused a larger concentration gradient between 2 phases at the polymer precipitation step; this resulted in decreased encapsulation efficiency (from 34.19% to 25.67%) and a greater initial burst (from 61.71% to 70.05%). SKL-2020-loaded PLGA microparticles prepared with different fabrication conditions exhibited unique release patterns of SKL-2020. High PVA concentration and high drug loading led to an initial burst effect by rapid drug diffusion through the polymer matrix. Since PLGA microparticles enabled the slow release of SKL-2020 over 1 week in vitro and in vivo, more convenient and comfortable treatment could be facilitated with less frequent administration. It is feasible to design a release profile by mixing microparticles that were prepared with different fabrication conditions. By this method, the initial burst could be repressed properly and drug release rate could decrease.

• 폴리머
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• 제28권4호
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• pp.335-343
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• 2004

카뮤스틴 (1,3-bis(2-chloroethy1-nitrosourea, BICNU)은 뇌종양 치료를 위하여 임상적으로 사용되는 약물로 짧은 생물학적 반감기를 가지고 있어 장기방출에 적합하지 않다. 하지만, poly(D,L-lactide-co-glycolide) (PLGA)는 벌크 분해 특성으로 인해 약물의 장기방출에 유용하며, PLGA의 유도체인 글리콜라이드 단량체는 독성이 없고 PLGA와 유사한 생분해성을 가지고 있어 BICNU의 방출조절에 이용된다. 이 실험에서 BICNU를 함유한 PLGA 웨이퍼는 일반적인 직접압축법에 의해 제조한 후 BICNU의 방출거동과 웨이펴의 분해속도를 전자주사현미경, 핵자기공명장치 그리고 젤투과크로마토그래피를 통해 관찰하였다. 또한, 글리콜라이드 단량체의 함량변화에 따른 다중층 웨이퍼를 제조하여 단일층 웨이퍼와의 방출거동을 비교하였다. 이러한 결과들로부터 BICNU를 함유한 PLGA 웨이퍼의 약물방출은 BICNU와 글리콜라이드 단량체의 함량이 증가할수록 증가하였고, 다중층 웨이퍼에서 외부층의 글리콜라이드 단량체와 BICNU가 약물방출 거동과 분해속도에 영향을 미친다는 것을 확인하였다.

• 폴리머
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• 제26권5호
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• pp.691-700
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• 2002

항암제가 함유된 생분해성 고분자 디바이스를 이용한 국소전달요법은 종양 부위에 고농도로 약물을 전달시킬 수 있는 이유로 약물의 효율성을 증가시킬 수 있다. 1,3-bis(2-chloroethyl)-1-nitro-sourea (BCNU, carmustine)는 뇌종양 치료를 위하여 가장 일반적으로 사용되는 화학요법적 약물이다. 표적 부위까지 항암제를 효과적으로 전달하기 위한 이식제의 설계는 중요한 인자이다. 본 연구에서 약물의 방출경향을 조절하기 위해서 생분해성 웨이퍼의 첨가제와 다양한 제형 변화로부터 BCNU의 방출패턴을 조사하였다. 각각 3.85, 10, 20 및 30%의 BCNU를 함유한 PLGA 웨이퍼를 다양한 형태(직경 3, 5 및 10 mm, 두께 0.5, 1 및 2 mm)로 직접 압축성형법에 의해 제조하였다. 생체외 방출실험에서 BCNU 함유 PLGA 웨이퍼로부터 약물 방출거동은 웨이퍼의 포기 약물 함유량, 무게, 직경, 두께, 부피, 표면적 및 PLGA 분자량뿐만 아니라 첨가제의 종류와 같은 다양한 변수로 조절했다. 웨이퍼로부터 약물의 방출은 BCNU 함유량 및 염화나트륨 (NaCl)과 폴리엔비닐피롤리돈 (PVP)이 증가할수록 촉진되었다. 또한, BCNU가 함유된 PLGA 웨이퍼의 무게와 형태변화에 대한 조사를 통하여 다양한 기하학적 인자들과 첨가제의 효과를 고찰하였다.

• Macromolecular Research
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• 제16권5호
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• pp.418-423
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• 2008

Poly[(R)-3-hydroxy butyrate] (PHB) and methoxy poly(ethylene glycol) (mPEG) were conjugated by the transesterification reaction with tin(II)-ethylhexanoate (Sn(Oct)-II) as a catalyst. Hydrophobic PHB and hydrophilic mPEG formed an amphiphilic block copolymer which was formed with the self-assembled polymeric micelle in aqueous solution. In this study, we tried to determine the optimum ratio of hydrophobic/hydrophilic segments for controlled drug delivery. The particle size and shape of the polymeric micelle were measured by atomic force microscopy (AFM) and transmission electron microscopy (TEM). Their size were 61-102 nm with various block ratios. Griseofulvin was loaded in the polymeric micelle as a hydrophobic model drug. The loading efficiency and release profile were measured by high performance liquid chromatography (HPLC). The model drug in our system was constantly released for 48 h.

• 약학회지
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• 제39권2호
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• pp.185-192
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• 1995

Flurbiprofen, one of potent nonsteroidal antiinflammatory drugs, has several systemic side effects due to dose dumping effect following oral administration of its conventional solid dosage forms. To reduce these side effects and to sustain therapeutic concentration of the drug, matrix tablets of flurbiprofen were prepared and evaluated for sustained release from the tablets. The matrix tablets of flurbiprofen were prepared with Eudragit, Pluronic, (anhydrous) lactose and colloidal silicon dioxide employing two different preparation methods, wet granulation and direct compression. The dissolution rates of the tablets were evaluated using KP 2 method. Formulation factors that affected dissolution rates of flurbiprofen were the type and content of Eudragit, the type and content of Pluronic, and the tablet preparation method. Several formulations of the matrix tablets showed dissolution patterns close to the simulated profile using pharmacokinetic parameters of flurbiprofen.