• Journal of Pharmaceutical Investigation
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• v.37 no.2
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• pp.95-99
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• 2007

To develop topical nitroglycerin (NTG) preparation far chronic anal fissure treatment, the release rate of NTG should be controlled carefully. For this, microemulsion was prepared from the phase diagram construction with Cremophor ELP, ethanol and Labrafil $M1944CS^{(R)}$ and the topical gel was prepared by dispersing NTG containing microemulsion into hydrophilic polymers. in viかo release characteristics were evaluated with Franz diffusion cell using cellulose membrane and compared with control hydrogels. The release rate of NTG was followed $1^{st}$ order kinetics and, when comparing the NTG release from control hydrogel with that from the microemulsion-based hydrogel, the NTG release rate was controlled by the content of polymers within continuous phase and the concentration of dispersed phase.

• Journal of Pharmaceutical Investigation
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• v.35 no.3
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• pp.207-224
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• 2005

The objective of this study was to explore the principles of SUPAC-SS and its regulatory application in handling postapproval changes to nonsterile semisolid dosage forms. The types of postapproval changes that SUPAC-SS described were modifications in formulation (components and composition), batch size, manufacturing equipment & process, and the site of manufacturing. SUPAC-SS defined the levels of postapproval changes and what chemistry, manufacturing, and control tests should be conducted for each change level. The guidance also specified several occasions the manufacturers should perform in vitro release test (Franz cell diffusion test) and/or in vivo bioequivalence test. Finally, SUPAC-SS classified appropriate filing forms to be used in supporting postapproval changes. It was crystal clear that SUPAC-SS helped maintain the safety and quality of approved semisolid dosage forms when they were subject to certain postapproval changes. The availability of SUPAC-SS made contributions to reducing regulatory burdens of the industry, as well as expediting the postapproval process of regulatory agencies. This study also shed light on the background of relevant pharmaceutical sciences that the SUPAC-SS guidance adopted. Finally, the KFDA and the industry were strongly urged to implant a similar guidance in handling postapproval changes to semisolid dosage forms available in the Korean marketplace.

• Journal of Pharmaceutical Investigation
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• v.35 no.1
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• pp.7-16
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• 2005

Gardeniae Fructus is consisted of geniposide and it's derivatives. For the purpose of treatment of skin disease, geniposide and hydrolyzed products (HP) of Gardeniae Fructus were studied on skin permeation and cross1inking with biological tissue. The hydrolyzed products (HP) and active ingredients of Gardeniae Fructus were identified and investigated about skin permeability. Genipin has provided low cytotoxic cross1inking reagents and formed stable and biocompatible crosslinked products. The permeation enhancing effects of geniposide and genipin under the hydrolyzed products of cream and hydrogel preparations were tested using Franz type diffusion cell and the skin of hairless mouse. The remaining proportions of geniposide and genipin were measured in the hydrolyzed products of cream and hydrogel preparations. The crosslinking of epidermic and endodermic tissue with genipin under the hydrolyzed prodcuts of cream and hydrogel preparation was observed using light microscopy. Increased absorption ratio of the skin of hairless mouse about genipin was higher than that of geniposide. Loads at break, tensile strengths and skin permeation rate of the hydrolyzed products (HP) of cream and hydrogel preparations were higher than the nonhydrolyzed products (NHP). The hydrolyzed products (HP) of cream and hydrogel of Gardeniae Fructus Extracts were proper preparations and crosslinking agents to increase the transdermal absorption with epidermic and endodermic tissue.

• YAKHAK HOEJI
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• v.44 no.6
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• pp.595-600
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• 2000

Transdermal delivery of ketorolac tromethamine, a potent non-narcotic analgesic, through human cadaver skin was investigated in vitro. A mixture of ethanol/water (40/60) containing 0, 1, 3, 5, and 8 (w/v)% L-menthol were used as a vehicle and penetration enhancer respectively. The permeation of ketorolac through human cadaver skin from saturated drug solution was evaluated at $37^{\circ}C$ with modified Franz diffusion cell. The in vitro skin flux and lag time were $1.23\;{\pm}\;0.11\;{\mu}g/cm^2{\cdot}hr$ and $5.56\;{\pm}\;0.34\;hr$, respectively. The cumulative amount of penetrated ketorolac containing L-menthol in ethanol/water (40/60) binary system was increased by the following order; 3%, 5%, 8%, 1%, 0%, and the lag time was decresed by the following order; 3%, 5%, 8%, 0%, 1%. The results suggested that a potential use of 3% L-methol is an effective penetration enhancer of ketorolac tromethamine through the human cadaver skin.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.29 no.1
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• pp.169-184
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• 2003

비타민 C(L-ascorbic acid)는 강한 항산화성, 피부에 대한 높은 안전성으로 인해 피부의 노화방지, 미백, 주름 개선 등의 기능성 화장품 원료로써 많은 관심이 있는 물질이지만, 화학적으로 매우 불안정하여 쉽게 산화, 분해되므로 화장품 제형으로 포함시키는데 곤란한 문제가 있다. 본 연구에서는 비타민 C 의 안정성에 대한 단점을 보완하기 위하여 생체 및 피부 친화성이 우수한 무기물을 사용하여 비타민 C 를 캡슐화(encapsulation)한 분말상의 유-무기 복합물질 Vitabrid-C 를 합성하고, 이를 함유하는 피부 미백용 트윈케익 파우더를 개발하였다. 우선 Vitabrid-C 는 수용액상에서 비타민 C 를 수화된 산화아연(ZnO)으로 1 차 캡슐화하여 나노입자를 형성시키고, 그 표면을 실리카(silica)나노 입자로 한번 더 코팅하여 표면의 껍질이 다공특성을 갖는 분말을 제조함으로써 완성하였다. 이렇게 제조된 Vitabrid-C는 순수 비타민 C 에 비해 우수한 안정성을 보였으며, 캡슐 내 비타민 C 가 서서히 방출되는 서방특성을 발휘하였다. 또한 Vitabrid-C는 입자의 크기가 미세하고 균일하여 트윈케익 처방에 용이하게 적용할 수 있었다. Vitabrid-C와 순수 비타민 C의 생화학적 동등성에 대한 평가는 tyrosinase 억제능(L-DOPA oxidase 억제) 및 DPPH항산화 실험을 통하여 비교하였다. 트윈 케익 처방에 적용된 Vitabrid-C 에서 비타민 C 의 피부 투과경향을 Franz diffusion cell 법을 이용하여 확인하였다 또한 Vitabrid-C가 포함된 트윈케익을 건강한 피부를 가진 25 세 이상되는 여성의 전박에 색소 침착을 유도한 후 피부색 개선 효과 평가를 통해 임상적 효능을 평가하였다.

• Archives of Pharmacal Research
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• v.29 no.5
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• pp.412-417
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• 2006

Triamcinolone acetonide (TA) is a corticosteroid that is used in the systemic and topical treatment of many inflammatory diseases. In this study, a phonophoretic drug delivery system was designed to enhance the TA permeability and the influence of ultrasound was examined. In order to establish the transdermal delivery system for TA, a hydrophilic carbopol gel containing TA was prepared after adopting phonophoresis. A permeation study through mouse skin was performed at $37^{\circ}C$ using a Franz diffusion cell, and the ultrasound treatment was carried out for 10 h. The level of TA permeation through the skin was evaluated under various ultrasound conditions including the frequency (1.0, 3.0 MHz), intensity (1.0, $2.5W/cm^2 $), and duty cycle (continuous, pulse mode) using a 0.5% TA gel. The highest permeation was observed under the ultrasound treatment conditions of low frequency, high intensity, and in continuous mode.

• Archives of Pharmacal Research
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• v.19 no.6
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• pp.435-440
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• 1996

The effect of benzalkonium chloride on skin permeability of partially modified antisense phosphorothioate oligonucleotides (PS-ODN), which are designed as scar formation inhibitor, was investigated using Franz Diffusion Cell. When the concentration ratio of PS-ODN-quarternary ammonium salt complex is more than 1:100, the apparent partition coefficient (APC) of each complex was increased in the following order; tetraphenyl phosphonium chloride (TPP) < cetyltrimethyl ammonium bromide(CTAB) < benzalkonium chloride (BZ). The permeability of PS-ODN through the rat skin increased in the presence of BZ. The fluxs of PS-ODN with BZ were increased by addition of Pluronic F 68 or Triton X-100 to phosphate buffered saline (PBS), respectively. When the mole ratio of PS-ODN to BZ is 1:10, the fluxs penetrated of PS-ODN with BZ was greatest. The increase of the permeability in the presence of BZ might be due to the formation of lipophilic ion-pair complex between PS-ODN and BZ. By regulation of mole ratio of PS-ODN to BZ, the development of topical dosage forms using PS-ODN as scar formation inhibitor will be possible with minimal systemic exposure.

• Journal of Pharmaceutical Investigation
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• v.28 no.1
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• pp.43-50
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• 1998

Niosomes are vesicles formed from synthetic non-ionic surfactants, offering an alternative to chemically unstable and expensive liposomes as a drug carrier. Non-ionic surfactant and cholesterol mixture film leads to the formation of vesicular system by hydration with sonication method. The formation of niosome was ascertained by negative staining of TEM. The entrapment efficiency of niosomal suspension was gradually increased with increasing the ratio of cholesterol to surfactant. It was found that the niosome with 6 : 4 (polyoxyethylene 2-cetyl ether: cholesterol) ratio was more stable than those with other ratios. The topical application of acyclovir(ACV) in the treatment of herpes simplex virus type 1(HSV-1) skin disease has a long history. There are an increasing number of reports, however, in which topical ACV therapy is not as effective as oral administration. Lack of efficacy with topical ACV has been hypothesized to reflect the inadequate delivery of drug to the skin. We investigated the permeation of niosome containing $[^{3}H]ACV$ in hairless mouse skin using Franz diffusion cell model. Permeation coefficient(P) of aqueous ACV was $6.7{\times}10^{-4}\;(cm/hr)$ and that of ACV in niosome was $23.4{\times}10^{-4}\;(cm/hr)$, suggesting about 3.5 times increase in the transdermal permeation.

• Archives of Pharmacal Research
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• v.21 no.5
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• pp.503-507
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• 1998

Percutaneous absorption and model membrane variations of melationin (MT) in aqueous-based propylene glycol and $2-hydroxypropyl-{\beta}-cyclodextrin $vehicles were investigatted. the excised hairless mouse skin (HMS) and two synthetic ethylene vinyl acetate (EVA) and microporous polyethylene (MPE) were selected as a model membrane. the solubility of MT was determined by phase equilibrium study. the vertical $Franz{\circledR}$ type cell was used for diffusion study. The concentration of MT was determined using reverse phse HPLC system. The MT solubility was the highest in a mixture of PG and $2-HP{\beta}CD$. The percutaneous absorption of MT through excised HMS increased as the solubility increased. However, the permeability coefficient decreased and then slightly increased in mixture of PG and $2-HP{\beta}CD$. On the other hand, both flux and permeability coefficient through EVA membrane decreased as the solubility increased. No MT was detected over 12 h after starting diffusion through MPE membrane. The flux of MT was dependent on the type of membrane selected. Flux of MT was greatest in excised HMS followed by EBA and MPE membrane. Flux of MT through EVA membrane was 5-20 times lower when compared to excised HMS. Interestingly, volumes of donor phase when MPE membrane was used, significantly increased during the study period. the HMS might be applicable to expect plasma concentration of MT in human subjects based on flux and pharmacokinetic parameters as studied previously. the current studies may be applied to deliver MT transdermally using aqueous-based vehicles and to fabricate MT dosage forms.

• Polymer(Korea)
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• v.36 no.4
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• pp.420-426
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• 2012

In this study, we prepared polymer micelles containing quercetin and rutin, known as antioxidants, using poly(${\varepsilon}$-caprolactone)-b-poly(ethylene glycol), and evaluated in vitro skin permeation of the active materials. Quercetin and rutin loaded micelles were characterized by DSC (differential scanning calorimetry), HPLC (high performance liquid chromatography) and DLS (dynamic light scattering) measurements. The particle size of the polymer micelles increased in a concentration dependent manner (0.5~2.0% PCL-b-PEG). The Zeta potential of quercetin and rutin loaded micelles remained constant. To evaluate the skin penetration of PCL-b-PEG micelles, Franz diffusion cell experiment was performed. The aqueous solutions of quercetin and rutin were used as the control groups. Quercetin and rutin loaded PCL-b-PEG micelles showed more efficient skin permeation than the control groups. Safety assessment (patch test) of quercetin and rutin loaded PCL-b-PEG micelles on skin was performed to test application possibility of the polymer micelles to cosmetics. Any adverse symptoms were not observed.