• Journal of Pharmaceutical Investigation
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• 제22권2호
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• pp.77-96
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• 1992

In recent years intranasal administration of drugs has received great attention as a convenient and efficent method of drug delivery because of its potential to improve the systemic effect of substances with a poor oral bioavailability. In addition to offering advantages such as rapid absorption, fast onset of action and avoiding the first -pass effect, it provides for delivery of drugs from very lipophilic drugs such as steroids to polar and hydrophilic drugs such as peptides and proteins. However, little is still known about the nature of various barriers existing in the nasal mucosae as well as mechanism by which these molecules are absorbed. This review article therefore intends to discuss nasal physiology, experimental methods and evaluation of absorption from the nasal cavity, factors influencing nasal absorption, mechanism of nasal absorption, approaches to improve the residence time and to obtain the sustained-release effect of intranasally administered drugs, promoters and mechanism for the enhancement of nasal absorption, Several examples for intranasal delivery of various systemically effective drugs will be reviewed and illustrated. Drug metabolism in the nasal mucosae and problems associated with intranasal administration of drugs will be also discussed.

• Journal of Pharmaceutical Investigation
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• 제40권6호
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• pp.321-332
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• 2010

Growing interest in the nasal route as a drug delivery system calls for a reliable in vitro model which is crucial for efficiently evaluating drug transport through the nasal cells. Various in vitro cell culture systems has thus been developed to displace the ex vivo excised nasal tissue and in vivo animal models. Due to species difference, results from animal studies are not sufficient for estimating the drug absorption kinetics in humans. However, the difficulty in obtaining reliable human tissue source limits the use of primary culture of human nasal epithelial cells. This shortage of human nasal tissue has therefore prompted studies on the "passage" culture of nasal epithelial cells. A serially passaged primary human nasal epithelial cell monolayer system developed by the air-liquid interface (ALI) culture is known to promote the differentiation of cilia and mucin gene and maintain high TEER values. Recent studies on the in vitro nasal cell culture systems for drug transport studies are reviewed in this article.

• Archives of Pharmacal Research
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• 제17권2호
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• pp.57-59
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• 1994

The effect of sodium taurodihydrofusidate (STDHF) on drug permeation across nasal mucosa was studied in vitro using Ussing type diffusion chamber. Disodium cromoglicate (DSCG, M.W.5123) and fluorescein isothiocyanate-dextran (FD) of different molecular wieghts (M.W. 4400-71200) were used as model drugs. Pemeation profiles of DSCG and FDs showed a typical pseudo steady-state curve with short lag time. The pemeability coefficient of FD (M.W. 9400) sigmodially increased with increasing STDHF concentration. It also enhanced the DSCG pemeation. Interestingly the enhancement efficacy was independent of molecular weight of penetrants.

• Journal of Pharmaceutical Investigation
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• 제22권4호
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• pp.251-266
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• 1992

A major problem with the peptide-based drugs is that these drugs must generally be administered by injection. Therefore, there is considerable research interest in alternative routes of delivery, such as buccal, nasal, gastrointestinal route and etc. Site-specific drug delivery to the colon, as an alternative to parenteral drug delivery, is of interest for the delivery of peptide-based drugs as well as the delivery of low molecular weight drugs for the treatment of colonic disease, This review describes some considerations of colon-specific drug delivery using hydrogels.

• Journal of Pharmaceutical Investigation
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• 제40권spc호
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• pp.33-43
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• 2010

Hyaluronic acid (HA) is a biodegradable, biocompatible, non-toxic, non-immunogenic and non-inflammatory linear polysaccharide, which has been used for various medical applications including arthritis treatment, wound healing, ocular surgery, and tissue augmentation. Because of its mucoadhesive property and safety, HA has received much attention as a tool for drug delivery system development. It has been used as a drug delivery carrier in both nonparenteral and parenteral routes. The nonparenteral application includes the ocular and nasal delivery systems. On the other hand, its use in parenteral systems has been considered important as in the case of sustained release formulation of protein drugs through subcutaneous injection. Particles and hydrogels by various methods using HA and HA derivatives as well as by conjugation with other polymer have been the focus of many studies. Furthermore, the affinity of HA to the CD44 receptor which is overexpressed in various tumor cells makes HA an important means of cancer targeted drug delivery. Current trends and development of HA as a tool for drug delivery will be outlined in this review.

• Journal of Pharmaceutical Investigation
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• 제22권3호spc1호
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• pp.1-15
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• 1992

• Journal of Pharmaceutical Investigation
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• 제36권6호
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• pp.363-369
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• 2006

Granisetron is a selective 5-HT3 receptor antagonist that is used therapeutically for the prevention of vomiting and nausea associated with emetogenic cancer chemotherapy. Although this drug is commercially available for intravenous and oral dosage, there is a need for intranasal delivery formulations in specific patient populations in which the use of these dosage forms may be unfeasible and/or inconvenient. A rapid and specific high-performance liquid chromatography method with mass spectrometric detection(LC-MS) was developed and validated for the analysis of granisetron in plasma after nasal administration in rats. This method has been validated for concentrations ranging from 5 to 1000 ng/ml with simple treatment. This technique has high level reproducibility, accuracy, and sensitivity. The method described was found to be suitable for the analysis of all samples collected during preclinical pharmacokinetic investigations of granisetron in rats after nasal administration. This study was aimed to investigate the feasibility of nasal delivery of granisetron for the elimination of vomiting. The effects of osmolarity, dosage volume at the same dose and applied dose on the nasal absorption of granisetron in rats were observed. No significant difference in the effect of osmolarity and dosage volume at the same dose was observed. As the applied dose of granisetron in nasal formulation increased, the absorption increased linearly. Based on these results it appears that only the applied dose(drug mass) determines the nasal absorption of granisetron. The bioavailability of granisetron on nasal administration of 4 mg/kg appeared to be comparable to that of intravenous administration of the same dose. These results suggest that granisetron can be efficiently delivered nasally and the development of nasal formulation will be feasible.

• Biotechnology and Bioprocess Engineering:BBE
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• 제6권4호
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• pp.212-230
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• 2001

Recent advances in recombinant DNA technology have resulted in development of many new protein drugs. Due to the unique properties of protein druges, they have to be delivered by parenteral injection Although delivery of protein drugs by other routes, such as pulmonary and nasal routes, has shown some promises, to date most protein drugs are administered by par-enteral routs. For long-term delivery of protein drugs by parenteral administration, they have been formulated into biodegradable microspheres. A number of microencapsulation methods have been developed, and the currently used microencapsulation methods are reviewed here, The microen-capsulation methods have been divided based on the method used. They are: solvent evapora-tion/extraction; phase separation (coacervation);spray drying; ionotropic gelation/polyelectrolyte complexation; interfacial polyumerization and supercritical fluid precipitation. Each method is de-scribed fro its applications, advantages, and limitations.

• Journal of Pharmaceutical Investigation
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• 제25권4호
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• pp.353-363
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• 1995

The purpose of this study was to investigate the intestinal and nasal absorption enhancement of cefotaxime (CTX) by ion-pairing with counterions and to design an effective oral and intranasal drug delivery system for antibiotics. Counterions for absorption promotion were cationic surfactants [cetylpyridinium chloride (CP), cetrimide (CT) and benzalkonium chloride (BA)]. In the presence of counterions, the apparent partition coefficient of cefotaxime was increased depending on the molar concentration of the counterions. Anion interference was observed for ion-pairing of cefotaxime with counterions because of the counterbalance between an anion and counterions. The present study employed the in situ simultaneous nasal and intestinal perfusion technique in rats. The apparent permeabilities $(P_{app})$ of cefotaxime were $1.43{\pm}0.04{\times}10^{-5}\;cm/sec(mean{\pm}S.E)$ in the nasal cavity and 0 in the jejunum, respectively, which indicated that the intrinsic absorptivity of cefotaxime was greater in the nasal cavity than in the jejunum. When ionupairing formers were used, the decreasing order of apparent cefotaxime permeability $(P_{app},\;10^{-5}\;cm/sec)$, corrected for surface area of absorption, was as followings: $BA\;(7.50{\pm}0.36)\;>\;CT\;(4.92{\pm}0.24)\;>\;CP\;(3.01{\pm}0.17)$ in the jejunum and $BA\;(22.31{\pm}1.36)\;>\;CP\;(18.24{\pm}0.81)\;>\;CT \;(16.22{\pm}1.87)$ in the nasal cavity. The increase in permeability of cefotaxime was about 13-fold in the rat nasal cavity and was marked in the rat jejunum for ion-pairing with counterions as compared to those without ion-pairing. The damages of jejunal and nasal mucosal membrane by counterions were observed within approximately 2hrs after removal of ion-pair of cefotaxime with counterions from the nasal cavity and jejunum. These results suggest that CP can be used as an ion-pairing former in the jejunum and CP and CT can be used as ion-pairing formers in the nasal cavity for cefotaxime, as well as for poorly absorbed drugs with a negative charge due to ionization.

• 대한기계학회논문집 C: 기술과 교육
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• 제2권2호
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• pp.73-80
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• 2014

상기도 내의 약물 전달을 알아보기 위하여 구강 호흡 시 공기유동에 대한 수치해석을 수행하였다. 상기도는 구강과 후두, 기관과 기관지로 구성되어 있다. 정밀 촬영한 CT 데이터로부터 의료영상 소프트웨어(Mimics)를 이용한 구분(segmentation)과 세심한 표면처리를 통하여 해부학적으로 정확한 모델을 만들 수 있었다. 이 3차원 컴퓨터 모델을 이용하여, 구강에서 기관지의 2번째 분지까지 이르는 유로의 수치 모델을 제작하였다. 수치해석은 상용 소프트웨어인 ANSYS/Fluent를 이용하여 계산하였다. 본 연구에 사용된 모델은 노즐이 부착되지 않은 상태에서 초당 250 mL를 흡입하는 정상 구강호흡 모델과 입구에 각각 20 mL/s, 40 mL/s, 60 mL/s의 유량을 갖는 노즐을 장착한 모델을 사용하였다. 전산 유동가시화 결과로부터, 노즐의 유량을 증가시킬수록 선회류의 발생 정도가 증가하여 구강 내 약물의 잔류 량은 증가하지만, 기관/기관지에 약물 도표는 균일하게 나타났다.