Evaluation of nitroglycerin and cyclosporin A sorption to polyvinylchloride- and non-polyvinylchloride-based tubes in administration sets

진수언,박정우,백홍,전승호,박상욱,황성주 한국약제학회 2018 Journal of Pharmaceutical Investigation Vol.48 No.6

We report the sorption evaluation method for injectable drugs administered using set tubes to evaluate the quality of the administration sets. The evaluation method using a peristaltic pump, so called pump method, was used for the kinetic sorption study. Nitroglycerin (NTG) and cyclosporin A (CSA) were selected as model drugs. The parameters of drug-diluted concentrations and flow rates were adapted to the clinically relevant values. Polyvinylchloride (PVC)- and non-PVC (PU and PO)-based tubes were cut to a fixed length of 1 m after removing the accessories in the administration sets. NTG and CSA were analyzed using high-performance liquid chromatography (HPLC) methods with ultraviolet (UV) detection. After the drug analyses, NTG and CSA sorption levels were calculated from the percentage values of the subtracted drug concentrations in samples from those in the diluted solutions. The average sorption levels and each sorption level at each sampling point were considered to compare the sorption levels in all administration set tubes. Both drugs showed high sorption levels in PVC- and PU-based administration set tubes. However, the drugs showed a minimum sorption potential of < 10% on PO-based tubes, which could be clinically acceptable. This suggests that the sorption evaluation methods for NTG and CSA could be promising standards for endorsing administration set tubes and for evaluating newly developed or designed polymeric alternatives. Additionally, PO could be an alternative and next-generation polymeric material for manufacturing administration set tubes.

Comparative effects of PEG-containing liposomal formulations on in vivo pharmacokinetics of streptokinase

진수언,김인숙,김종국 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.10

Streptokinase (SK) is an effective thrombolyticagent, but it has a short half-life due to its rapid eliminationfrom the body. In this study, we prepared and evaluatedpolyethyleneglycol (PEG)-based liposomal formulations(PEG-liposomes) containing SK with a view toward prolongingits circulatory half-life. SK-bearing liposomes (SKliposomes)were prepared using freeze–thaw method afterfilm hydration and extrusion techniques, composed ofphosphatidylcholine [egg phosphatidylcholine (EPC), dipalmitoylPC, or distearoyl PC], cholesterol and cholesterol-3-sulfate with or without PEG. Their physicochemicalproperties were characterized by the measurement of sizeand zeta potential and incorporation efficiency. SK-liposomalformulations were applied to rats through a femoral veinvia intravenous administration to compare the effects of liposomaldelivery and PEG on the half-life of SK in blood. Free SK was used as a control. SK activities in plasma weremeasured to estimate the amidolytic activity of SK-plasminogencomplex after rupturing liposomes with TritonX-100. Pharmacokinetic parameters were obtained from SKactivity-time profiles. The SK-liposomes had a homogenousdistribution of negatively charged nanoparticles at the rangeof 10–33 % of the incorporation efficiencies of SK. Amongthe SK-liposomes, SK-EPC- and SK-EPC/PEG-liposomeshad injectable diameters (\200 nm). SK was administeredas free SK, SK-EPC-liposomes, or SK-EPC/PEG-liposomesfor in vivo study. SK-EPC/PEG-liposomes had significantlygreater the t1/2, AUC?andMRT values of SK than SK aloneor SK-EPC-liposomes. These findings suggest that PEG-liposomalincorporation of SK enhances thrombolytic activityin vivo, and that such liposomes can be utilized to enhancethe pharmacokinetic profiles of other therapeutic proteinswith a short biological half-life.

광물 자원에서 유래된 원료 의약품 및 첨가제의 사례 연구

진수언,이장익,황성주,Jin, Su-Eon,Lee, Jangik Ike,Hwang, Sung-Joo 대한자원환경지질학회 2015 자원환경지질 Vol.48 No.3

약학 분야에서 점토광물은 점토광물 자체의 약리작용을 확인하고 원료의약품으로 활용하거나 희석제, 유화제, 점증제, 활택제 등 의약품 제형의 완성도를 높이는 첨가제로서 사용되고 있다. 벤토나이트(Bentonite), 카올린(Kaolin), 규산알루민산마그네슘(Magnesium aluminum silicate), 탤크(Talc) 등은 원료의약품 혹은 첨가제로서 활용 가능한 대표적인 점토 광물로 국내외 의약품 공정서에 수재되어 있고, 약학적 활용시 의약품등급으로 규제되고 있다. 본 논문에서는 공정서에 수재된 점토 광물을 중심으로 공정서의 규격을 확인하고, 점토광물의 특성 및 원료의약품 혹은 의약품 첨가제로서의 점토 광물에 대한 활용 사례를 소개하고자 한다. 결론적으로 점토광물을 제약산업에 활용하는 것은 점토광물의 고부가가치화를 위한 한 가지 방법이 될 수 있으며, 자원의 개발 및 활용이라는 측면에서 매우 유용할 것이라 사료된다. Clay minerals have been used in pharmaceutical industries as active ingredients and excipients without pharmacological activity such as diluents, emulsifying agents, viscosity-increasing agents, and lubricants. For example, bentonite, kaolin, magnesium aluminum silicate, and talc are generally and extensively used pharmaceutical ingredients, which are restrictedly regulated by Pharmacopoeias. We discuss the physicochemical and biopharmaceutical properties of clay minerals. In addition, we introduce the cases of pharmaceutical applications of clay minerals. From this review, pharmaceutical applications of clay minerals can be one of strategies for the development of high value-added products from clay minerals.

수액세트에 대한 약물흡착도 평가 가이드라인(안) 제안

진수언,전승호,박정우,백홍,박상욱,변효진,황성주 한국에프디시규제과학회(구 한국에프디시법제학회) 2016 FDC법제연구 Vol.11 No.1

Ocular delivery systems for the administration of antibody therapeutics

진수언,황성주 한국약제학회 2017 Journal of Pharmaceutical Investigation Vol.47 No.5

Antibodies (Abs) have been extensively used as a powerful tool for targeting proteins based on their immunologic functions such as antigen recognition and pathogen neutralization. In particular, monoclonal Abs (mAbs) and fragments can be promising drugs in clinics owing to their sensitivity and specificity. The controlled release of Ab drugs after local delivery would lead to their prolonged exposure at the disease site, thereby improving the disease condition. In this review, we illustrate the activity of clinically used anti-vascular endothelial growth factor drugs, including aflibercept (Eylea; Regeneron Pharmaceuticals, Bayer Pharma), bevacizumab (Avastin; Genentech, Novartis), and ranibizumab (Lucentis; Genentech, Novartis), in ocular diseases such as wet age-related macular degeneration and myopic choroidal neovascularization. For controlled and prolonged release of the aforementioned drugs after ocular administration, recent approaches using liposomes, hydrogels, and nanoparticles have been introduced. In addition, the evaluation methods to meet the requirements of clinically used Abs are discussed. On the basis of the findings of our review, we can suggest that an ocular delivery system can be a promising platform to overcome the limitations associated with clinically used Abs.

Development of Coated Nifedipine Dry Elixir as a Long Acting Oral Delivery with Bioavailability Enhancement

최재윤,진수언,박유미,이효종,박요한,맹한주,김종국 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.10

To develop the long acting nifedipine oral delivery with bioavailability enhancement, a nifedipine dry elixir (NDE) containing nifedipine ethanol solution in dextrin shell was prepared using a spray-dryer, and then coated nifedipine dry elixir (CNDE) was prepared by coating NDE with Eudragit acrylic resin. The physical characteristics and bioavailability of NDE and CNDE were evaluated, and then compared to those of nifedipine powder. NDE and CNDE, which were spherical in shape, had about 6.64 and 8.68-8.75 μm of geometric mean diameters, respectively. The amount of nifedipine dissolved from NDE for 60 min increased about 7- and 40-fold compared to nifedipine powder in pH 1.2 simulated gastric fluid and pH 6.8 simulated intestinal fluid, respectively. Nifedipine released from CNDE was retarded in both dissolution media compared with that from NDE. After oral administration of NDE, the Cmax and AUC_(0→8h) of nifedipine in rat increased about 13- and 7-fold, respectively, and the T_max of nifedipine was reduced significantly compared with those after oral administration of nifedipine powder alone. The AUC_(0→8h) and T_max of nifedipine in CNDE increased markedly and the C_max of nifedipine in CNDE was significantly reduced compared to those in NDE. It is concluded that CNDE, which could lower the initial burst-out plasma concentration and maintain the plasma level of nifedipine over a longer period with bioavailability enhancement, might be one of potential alternatives to the marketed long acting oral delivery system for nifedipine.

Comparison of adhesion and dissolution of fentanyl patches: FentadurⓇ and Durogesic DTransⓇ

김택선,진수언,선보경,김민수,황성주 한국약제학회 2015 Journal of Pharmaceutical Investigation Vol.45 No.5

Fentanyl is a potent opioid used as an analgesic for pain therapy. Fentanyl patches have been developed using patch design technologies that use the transdermal route. The aim of this study was to compare the adhesion and dissolution properties of two fentanyl patches, Fentadur Ⓡ (Pfizer Inc., USA) and Durogesic DTransⓇ (Janssen- Cilag, Inc., USA), which were designed as a reservoir and a matrix, respectively. For the characterization of fentanyl patches, a 180 peel adhesion test and a dissolution test were performed at 12 and 100 lg/h of fentanyl patches. Specifically, the dissolution of fentanyl patches was tested at 32 and 40 ˚C using the USP apparatus 6 and the released fentanyl was analyzed using LC–MS/MS. FentadurⓇ and Durogesic DTransⓇ had acceptable adhesion forces over 150 gf using 12 mm of fentanyl patches. Comparing adhesion forces of FentadurⓇ and Durogesic DTransⓇ, FentadurⓇ had lower adhesion force values than Durogesic DTransⓇ. The release of fentanyl in FentadurⓇ was lower than that in Durogesic DTransⓇ, except for 100 lg/h FentadurⓇ at 40 ˚C over 12–48 h. The results show that FentadurⓇ and Durogesic DTransⓇ had the different properties of adhesion and dissolution, which could be critical factors for the prediction of clinical use.

Isolation and Identification of Steroidogenic Peptides from Calf Spleen

지준필,김종국,진수언,반은미,이효종,박유미,박요한,맹한주,김형태 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.4

Since women with climacteric syndrome have significantly lower serum levels of estradiol and other related hormones, hormone replacement therapies (HRT) such as estrogen are needed to lessen symptoms. However, HRT can often cause severe adverse effects that include many cancers and stroke. Therefore, new and novel approaches to relieve climacteric syndrome still need to be developed. The aim of this study was to identify biologically active peptides from calf spleen that are responsible for stimulating biosynthesis of steroid hormone and to explore the potential of isolated peptides as therapeutic agents for menopausal syndrome. The reverse phase HPLC system was used to isolate active compounds from calf spleen extract, a cell culture system was used to screen the activity of stimulating hormone secretion, and Matrix-Assisted Laser Desorption/Ionization (MALDI) mass spectrometry was used for molecular weight determination. In the present study, two calf steroidogenic peptides, CSP-1 (MW; 4.655 kDa) and CSP-2 (MW; 8.331 kDa), were isolated and identified from calf spleen and may be putative climacteric syndrome therapeutic agents.

인체 혈장 중 칼시트리올의 효소면역 분석법 검증 및 단회투여 후 약물동태 연구

김예태 ( Ye Tae Kim ),진수언 ( Su Eon Jin ),김현기 ( Hyun Ki Kim ),신백기 ( Baek Ki Shin ),정의현 ( Ui Hyeon Jeong ),김종국 ( Chong Kook Kim ),박정숙 ( Jeong Sook Park ) 韓國藥劑學會 2009 Journal of Pharmaceutical Investigation Vol.39 No.4

학술 7 특별구두세션 : PA. 포스터세션 1 ; 의약품 설계기반 품질 시스템( QbD)을 위한 Design Space 도출 방법 연구

최규효 ( Gyu Hyo Choi ),박성민 ( Sung Min Park ),신상문 ( Sang Mun Shin ),정성훈 ( Seong Hoon Jeong ),김민수 ( Min Soo Kim ),진수언 ( Su Eon Jin ),황성주 ( Whang ) 한국품질경영학회 2014 한국품질경영학회 학술대회 Vol.2014 No.2

1. 목적 · QbD (Quality by Design) 기반의 제품개발 및 품질관리는 국재적인 기준이 되어가는 추세로서 미국 및 EU의 규재기관과 대형 제약사들은 이미 본격적인 시행/실행 단계에 있으나 국내의 경우 전반적인 준비가 미흡한 실정이다. 국내 제약회사의 경우, 특히 Design Space 도출에 어려움을 겪고 있기 때문에 DoE (Design of Experiment)의 분석 체계를 통한 Design Space의 도출이 필요하다. 2. 연구설계/ 방법론/ 접근방법 · 품질 도구를 활용하여 체계적으로 CPP 및 CQA를 도출하는 방법 · DoE를 적용하여 보다 효율적으로 Design Space를 도출하는 방법 3. 연구결과 · 기존의 제약회사는 One at a time과 같은 방법을 통해 Design Space를 도출하였기 때문에 불필요한 실험 비용 및 시간이 소비되는 문재를 가지고 있다. 따라서 본 연구에서는 DoE를 적용하여 보다 효율적인 방법으로 Design Space를 도출할 뿐만 아니라 상호작용까지 고려할 수 있는 방법을 제시 4. 실무적 시사점 · DoE를 적용하여 Design Space를 도출함으로서 국내의 제약업체는 비용 및 시간의 소비를 최소화 함 5. 독창성/ 가치 · 의약품 생산 공정에서 품질의 보증을 효과적으로 달성하기 위하여 국내 실정에 맞는 구체적인 의약품 QbD 가이드라인 마련이 필요하기 때문에 본 연구의 QbD 절차 적용 사례를 통해 구체적인 QbD 가이드라인 도입의 근간을 마련하고자 함