Solid Dispersion as a Strategy to Improve Drug Bioavailability

박준형,전명관,조훈,최후균,Park, Jun-Hyung,Chun, Myung-Kwan,Cho, Hoon,Choi, Hoo-Kyun The Korean Society for Biotechnology and Bioengine 2011 KSBB Journal Vol.15 No.6

Solid dispersion is one of well-established pharmaceutical techniques to improve the dissolution and consequent bioavailability of poorly water soluble drugs. It is defined as a dispersion of drug in an inert carrier matrix. Solid dispersions can be classified into three generations according to the carrier used in the system. First and second generations consist of crystalline and amorphous substances, respectively. Third generation carriers are surfactant, mixture of polymer and surfactants, and mixture of polymers. Solid dispersions can be generallyprepared by melting method and solvent method. While melting method requires high temperature to melt carrier and dissolve drug, solvent method utilizes solvent to dissolve the components. The improvement in dissolution through solid dispersions is attributed to reduction in drug particle size, improvement in wettability, and/or formation of amorphous state. The primary characteristics of solid dispersions, the presenceof drug in amorphous state, could be determined by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and fourier-transformed infrared spectroscopy (FTIR). In spite of the significant improvement in dissolution by solid dispersion technique, some drawbacks have limited the commercial application of solid dispersions. Thus, further studies should be conducted in a direction to improve the congeniality to commercialization.

폐쇄성 수면 무호흡 환자에서 임시 하악 전방 이동 장치를 이용한 치료결과 분석

박준형,오수석,홍종락,김창수,팽준영,Park, Joon-Hyung,Oh, Suseok,Hong, Jongrak,Kim, Chang-Soo,Paeng, Jun-Young 대한악안면성형재건외과학회 2012 Maxillofacial Plastic Reconstructive Surgery Vol.34 No.6

Purpose: The aim of this study was to evaluate the effect of temporary mandibular advancement devices (MAD) in obstructive sleep apnea (OSA) patients Methods: 28 patients (male 21, female 7) undergoing temporary mandibular advancement device treatment for OSA were selected from 2011.01. to 2012.02. in the department of Oral & Maxillofacial Surgery at SamsungMedicalCenter. Treatment efficacy was determined by polysomnography (PSG) at baseline & after MAD delivery. The response group was defined as >50% Apnea-Hypopnea Index (AHI) reduction plus post-MAD AHI <10, and the non-response group was defined as <50% AHI reduction. The lateral cephalogram was analysed including SNA, SNB, UL, MPH, PAS, PASU, and PAST using V-ceph$^{TM}$ (Cybermed, USA). Results: The responsers were 23 patients, and non-responsers were 5 patients. The AHI was significantly reduced with temporary MAD ($8.08{\pm}7.93$) compared with baseline ($28.51{\pm}20.56$) in the response group (n=23). No significant difference was observed between pre MAD and post MAD except SNB on cephalometric analysis. Among 11 patients successfully treated with the temporary device, 9 patients said that using permanent device brings better effect too. Conclusion: These results indicate that the Temporary MAD could not be the only effective tools on OSA but also be used to predict patient's reactivity about permanent appliance treatment. Further studies are warranted to evaluate the relations between temporary MAD and permanent MAD.

국산 $^{18}F$-FDG Auto Sysnthesizer의 수율 향상과 성능 개선

박준형,임기섭,이홍진,정경일,이병철,이인원,Park, Jun-Hyung,Im, Ki-Seop,Lee, Hong-Jin,Jeong, Kyung-Il,Lee, Byung-Chul,Lee, In-Won 대한핵의학기술학회 2009 핵의학 기술 Vol.13 No.3

Purpose: 2-[$^{18}F$]Fluoro-2-deoxy-D-glucose ([$^{18}F$]FDG) particularly plays as a important role in Positron Emission Tomography (PET) imaging in nuclear medicine. Domestic [$^{18}F$]FDG auto synthesizers are installed in Seoul National University Bundang Hospital (SNUBH) at June 2008, these modules were known that it's synthetic yields were guaranteed in average $45{\pm}5%$ so far. To improve yields and convenience of domestic [$^{18}F$]FDG auto synthesizer, numerous trials in reaction time, base concentration, pressure and temperature were performed to increase [$^{18}F$]FDG yields. Materials and Methods: Several synthetic factors (temperature, time and pressure) and shortcoming were corrected based on many evaporation test. Syringe dispensing of tetra-butylammonium bicarbonate (TBAB) was replaced with micro pipette to prepare tetrabutyl ammonium fluoride salt ([$^{18}F$]TBAF). Troublesome refill of liquid nitrogen every 2 hours which was used to protect vacuum system was changed to charcoal cartridge, base guard filter. To monitor the volume of delivered $[^{18}O]OH_2$ from cyclotron by surveillance camera, we set up the volumetric vial on the cover of the module. In addition to, the recovery vial was added in [$^{18}F$]FDG production system to recover [$^{18}F$]FDG loss due to the leak of valve ($V_{13,14}$) in [$^{18}F$]FDG purification process. Results: When we used micro pipette for adding TBAB ($30\;{\mu}L$ in 12% $H_2O$ in acetonitrile), this quantitative dispensation has enabled to improve $5.5{\pm}1.7%$ residual fluorine-18 activity in fluorine separation cartridge compared to syringe adding. Besides, the synthetic yields of [$^{18}F$]FDG has increased $58{\pm}2.6%$ (n=19), $58{\pm}2.9%$ (n=14), $60%{\pm}2.5%$ (n=17) for 3 months. The life cycle of charcoal cartridge and base vacuum was 3 months prior to filling liquid nitrogen every 2 hours and additional side separator can prevent pump corrosion by organic solvent. After setting of volumetric indicator vial, the operator can easily monitor the total volume of irradiated $[^{18}O]OH_2$ from cyclotron. The recovery vial can be used for the stabilizer when an irregular [$^{18}F$]FDG loss was generated by the leak of valves ($V_{13,14}$). Conclusions: We has optimized appropriate synthetic conditions (temperature, time, pressure) in domestic [$^{18}F$]FDG auto synthesizer. In addition to, the remodeling with several accessories improve yields of domestic [$^{18}F$]FDG auto synthesizer with reliable reproducibility.

자동합성장치를 이용한 [$^{18}F$]Fallypride의 합성

박준형,문병석,이홍진,이효준,이인원,이병철,김상은,Park, Jun-Hyung,Moon, Byung-Seok,Lee, Hong-Jin,Lee, Hyo-Jun,Lee, In-Won,Lee, Byung-Chul,Kim, Sang-Eun 대한핵의학기술학회 2010 핵의학 기술 Vol.14 No.2

$[^{18}F]$Fallypride는 뇌의 도파민(dopamine) $D_2/D_3$ 수용체 (receptor)에 특이적으로 결합하는 길항제(antagonist)로 대뇌피질의 도파민 기능을 규명하기 위하여 많이 사용되어지는 방사성의약품이다. 그동안 발표되어진 자동 합성화 장치를 이용한 [$^{18}F$]Fallypride 합성은 20~30%의 낮은 합성 수율과 33~63 GBq/mmol의 낮은 비방사능이 보고되어졌고, 또, 상대적으로 긴 표지시간과 높은 농도의 base를 사용하기 때문에 다양한 부산물이 생성되어 정제의 어려움이 있어 임상에 사용되기에 한계가 많았었다. 본 연구에서는 다목적 F-18 합성장치인 GE TracerLab $FX_{FN}$ 모듈을 사용하여 base 농도를 최소화할 수 있는 연구를 수행하였고, [$^{18}F$]fallypride 합성에 적용하여 높은 합성수율과 비방사능(specific activity) 및 방사화학적 순도(radiochemical purity)를 합성하는 최적의 조건을 찾을 수 있었다. 이를 바탕으로 $66{\pm}1.4%$ (decay-corrected, n=28)의 높은 합성수율과 HPLC 분리, SPE 정제시간을 포함하여 총 $51{\pm}1.2$분에 빠르게 합성할 수 있었다. 합성 후, 품질관리 테스를 해 본 결과, 방사 화학적 순도는 95%이상, 비방사능은 166~470 $GBq/{\mu}mol$이었다. 본 연구에서 사용된 합성법은 [$^{18}F$]Fallypride를 이용한 dopamine $D_2/D_3$ 연구의 임상적 사용에 도움이 될 것이며, 낮은 농도의 base를 사용한 이 F-18 추출방법은 base에 민감한 전구체의 자동합성 생산에 유용할 것으로 사료된다. Purpose: $[^{18}F]$Fallypride plays an effective radiotracer for the study of dopamine $D_2/D_3$ receptor occupancy, neuropsychiatric disorders and aging in humans. This tracer has the potential for clinical use, but automated labeling efficiency showed low radiochemical yields about 5~20% with relatively long labelling time of fluorine-18. In present study, we describe an improved automatic synthesis of [$^{18}F$]Fallypride using different base concentration for routine clinical use. Materials and Methods: Fully automated synthetic process of [$^{18}F$]Fallypride was perform using the TracerLab $FX_{FN}$ synthesizer under various labeling conditions and tosyl-fallypride was used as a precursor. [$^{18}F$]Fluoride was extracted with various concentration of $K_{2.2.2.}/K_2CO_3$ from $^{18}O$-enriched water trapped on the ion exchange cartridge. After azeotropic drying, the labeling reaction proceeded in $CH_3CN$ at $100^{\circ}C$ for 10 or 30 min. The reaction mixture was purified by reverse phase HPLC and collected organic solution was exchanged by tc-18 Sep-Pak for the clinically available solution. Results: The optimal labeling condition of [$^{18}F$]Fallypride in the automatic production was that 2 mg of tosyl-fallypride in acetonitrile (1 mL) was incubated at $100^{\circ}C$ for 10 min with $K_{2.2.2.}/K_2CO_3$ (11/0.8 mg). [$^{18}F$]Fallypride was obtained with high radiochemical yield about $66{\pm}1.4%$ (decay-corrected, n=28) within $51{\pm}1.2$ min including HPLC purification and solid-phase purification for the final formulation. Conclusion: [$^{18}F$]Fallypride was prepared with a significantly improved radiochemical yield with high specific activity and shorten synthetic time. In addition, this automated procedure provides the high reproducibility with no synthesis failures (n=28).

발목재활 운동이 태권도 선수의 손상 받은 발목에 미치는 영향

박준형(Park Jun-Hyung),우지혜(Woo Ji-Hae),허진강(Hur Jin-Gang) 대한치료과학회 2010 대한치료과학회지 Vol.2 No.1

Objective: In Taekwondo, strengthening, muscular endurance, agility, and flexibility are all important muscle functions that determine an athlete's ability. This research aims to explore the effects of ankle rehabilitation exercise on ankle muscle strength, muscular endurance, lower balance ability and other functional abilities. Method: 30 taekwondo athletes suffering from ankle injuries were divided into 3 groups and put under rehabilitation exercises from Jun 1st. 2010 until August 31st, 2010. Examinations were conducted before and after, including strengthening test, muscular endurance test, lower balance test, and functional test. Results: Strengthening showed a significant difference(p<.05) among groups in dorsi-flexion, eversion at 60°/sec; a significant difference(p<.05) in eversion at 180°/sec. Lower balance showed a significant difference(p<.05) among groups in overall balance index, anterior/posterior index and medial/lateral index. Finally, for the functional test, there was a significant difference(p<.05) among groups in hopping and side hopping. Conclusion: Strengthening, muscular endurance, lower balance ability and functional ability showed greatest improvement in the proprioception exercise group. Hence, it can be concluded that the proprioception exercise group has positive effects when used as ankle rehabilitation exercise for injured athletes.

Solid Dispersion as a Strategy to Improve Drug Bioavailability

Jun-Hyung Park(박준형),Myung-Kwan Chun(전명관),Hoon Cho(조훈),Hoo-Kyun Choi(최후균) 한국생물공학회 2011 KSBB Journal Vol.26 No.4

Solid dispersion is one of well-established pharmaceutical techniques to improve the dissolution and consequent bioavailability of poorly water soluble drugs. It is defined as a dispersion of drug in an inert carrier matrix. Solid dispersions can be classified into three generations according to the carrier used in the system. First and second generations consist of crystalline and amorphous substances, respectively. Third generation carriers are surfactant, mixture of polymer and surfactants, and mixture of polymers. Solid dispersions can be generallyprepared by melting method and solvent method. While melting method requires high temperature to melt carrier and dissolve drug, solvent method utilizes solvent to dissolve the components. The improvement in dissolution through solid dispersions is attributed to reduction in drug particle size, improvement in wettability, and/or formation of amorphous state. The primary characteristics of solid dispersions, the presenceof drug in amorphous state, could be determined by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and fourier-transformed infrared spectroscopy (FTIR). In spite of the significant improvement in dissolution by solid dispersion technique, some drawbacks have limited the commercial application of solid dispersions. Thus, further studies should be conducted in a direction to improve the congeniality to commercialization.

수확 전 Cu-EDTA의 엽면살포 시기에 따른 ‘홍로’ 사과의 적엽 효과와 과실 품질 향상

박준형(Jun-Hyung Park),임헌규(Heon-Kyu Lim),신현석(Hyun-Suk Shin),손인창(In-Chang Son),김대일(Daeil Kim) 한국원예학회 2010 한국원예학회 학술발표요지 Vol.2010 No.5

근골격 운동 분석용 콘텐츠 개발을 위한 자세인식방법에 대한 연구

박준형(Jun-Hyung Park),박윤수(Yun-Su Park),허기택(Gi-Taek Hur) 한국콘텐츠학회 2021 한국콘텐츠학회 종합학술대회 논문집 Vol.2021 No.8

미술관의 사회적 역할 변화에 따라 나타나는 건축적 특성 분석

박준형(Park, Jun Hyung),김용승(Kim, Yong Seung) 대한건축학회 2017 대한건축학회 학술발표대회 논문집 Vol.37 No.2

반응기 혼합법에 의한 폴리올레핀/2D-나노시트 나노복합체 제조; 마스터배치를 이용한 폴리에틸렌 나노복합체

박준형(Jun Hyung Park),이동은(Dong Eun Lee),윤근병(Keun-Byoung Yoon) 한국고분자학회 2020 폴리머 Vol.44 No.6

옥타데실아민(octadecylamine, ODA)으로 개질한 MoS₂와 환원 그래핀옥사이드(rGO)가 분산된 폴리에틸렌 복합체를 마스터배치로 제조하였다. 마스트배치는 (n-BuCp)₂ZrCl₂/methylaluminoxane(MAO) 촉매계를 사용하여 에틸렌 중합 후 반응기 내에 개질한 2D-나노시트를 첨가하여 혼합하는 방법으로 제조하였다. 복합체의 열적, 기계적 성질 및 미세구조를 조사하였다. 폴리에틸렌 매트릭스에 2D-나노시트는 균일하게 분산되었으며, ODA 개질로 매트릭스와 2D-나노시트 계면의 접착력이 증가한 것으로 판단된다. 2D-나노시트 첨가에 따라 열적성질은 크게 변하지 않았지만, 열안정성 및 기계적 물성은 크게 증가하였다(5 wt% 첨가하였을 때 인장강도와 모듈러스는 각각 15% 및 100% 증가). 따라서 마스터배치를 사용한 나노복합체 제조는 고성능 폴리올레핀 제조에 유용할 것으로 판단된다. Polyethylene/modified 2D-nanosheets composites were fabricated via the masterbatch technique which was synthesized by reactor mixing under mild conditions using (n-BuCp)₂ZrCl₂/methylaluminoxane (MAO) catalyst. The 2D-nanosheets were modified with octadecylamine (ODA) for enhancement of dispersion and interaction with the polymer matrix. Microstructure, thermal and mechanical properties of composites were examined. The modified 2D-nanosheets were homogeneously dispersed across the composites and showed good interfacial adhesion between the modified 2D-nanosheets and polyethylene matrix. The thermal stabilities and mechanical properties of composites were significantly enhanced (e.g., up to 15% increase in tensile strength and 100% increase in Young’s modulus for composites containing 5 wt% 2D-nanosheets). Thus, the masterbatch technique was able to produce high-performance polyolefins.