PVP K30/Eudragit EPO에 의한 설레콕시브 고체분산체의 용출률 향상 및 특성

전대연(Dae Yeon Jeon),장지은(Ji Eun Jang),이정환(Jeong Hwan Lee),양재원(Jae Won Yang),박상미(Sang Mi Park),임동권(Dong Kwon Lim),강길선(Gil Son Khang) 한국고분자학회 2014 폴리머 Vol.38 No.4

셀레콕시브는 높은 결정성을 갖는 난용성 약물로서 이러한 난용성 약물의 용해도를 증진시키기 위해 고체분산법을 바탕으로 한 분무건조기를 이용하여 고체분산체를 제조하였다. PVP K30과 Eudragit EPO를 수용성 담체로 사용하였고 폴록사머 407은 계면활성제로 사용하였다. 제조된 셀레콕시브 고체분산체의 특성을 SEM, DSC, XRD 그리고 FTIR을 이용하여 확인하였다. SEM과 DSC 그리고 XRD를 통하여 셀레콕시브 고체분산체가 무정형임을 알 수 있었다. 제조된 고체분산체는 pH 1.2에서 용출을 실시하였으며 사판제인 Celebres 용출률을 비교하였으며 분무 건조를 통해 제조한 고체분산체가 Celebres 보다 용출률이 크다는 것을 확인하였다. We prepared nanoparticles containing insoluble celecoxib by the method of solid dispersions using a spray dryer to improve solubility of celecoxib. We used PVP K30 and Eudragit EPO as water-soluble carriers for the solid dis-persion, and polosamer 407 as a surfactant. Characterization of celecoxib solid dispersion was performed by scanning electron microscope(SEM), differential scanning calorimetry (DSC). X-ray diffraction (XRD) and Fourier-transform in frared spectroscopy (FTIR). The results of SEM, DSC and XRD demonstrated that celecoxib is amorphous in solid dis-persion. The dissolution rate measured in intestinal juice showed that the method of solid dispersion improved celecoxib solubility as compared with a conventional drug (Celebres). In conclusion, solid dispersion formulation prepared by a spray dryer would improve the solubility of celecoxib in oral administration.

수용성 고분자 PVP K-30로 제조된 레르카니디핀 고체분산체의 용출 특성

정현기(Hyun Ki Jeong),박진영(Jin Young Park),김수영(Su Young Kim),차세롬(Se Rom Cha),이선의(Seon Eui Lee),장나금(Na Keum Jang),이원택(Won Taek Lee),이진표(Jin Pyo Lee),송정은(Jeong Eun Song),강길선(Gilson Khang) 한국고분자학회 2016 폴리머 Vol.40 No.1

레르카니디핀 염산염은 디하이드로 피리딘의 칼슘채널 차단제로서 혈액이 체내에서 더 자유롭게 순환할 수 있도록 혈관을 확장시켜주는 고혈압 치료제이다. 레르카니디핀은 난용성 약물로 약물 전달 시스템에 적용하는데에 어려움이 많다. 이번 연구에 있어서 우리는 레르카니디핀에 수용성 고분자인 PVP K-30을 첨가하여 용출률을 개선시키기 위한 방법으로 분무건조와 회전증발법을 이용한 고체 분산체를 제조하였다. 또한 물질의 방출 거동은 in vitro로 평가하였으며 재료의 용출 거동 결과에서 고체분산체는 약물의 화학 구조 변화로 인하여 물질의 용해도가 증가되는 것으로 나타났다. Lercanidipine hydrochloride is a calcium channel blocker of the dihydropyridine, which opens the blood vessels for allowing the blood to circulate more freely around the body. Lercanidipine is a poorly water soluble drug and quite difficult to deliver. Taking this into account, in the study, we have designed lercanidipine loaded water soluble polymer PVP K-30 via solid dispersion method using spray drying and rotary evaporation to improve the dissolution properties. Further, the dissolution behavior of the materials were evaluated by in vitro assays. Results showed that solid dispersion has increased the dissolution properties of the materials owing to the change in the drug chemical structure.

고체분산체에 의한 펠로디핀의 용출을 개선과 서방성 경구제제

길영식,홍석천,유창훈,신현종,김종성 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.3

To improve the solubility of poorly water-soluble drug and to develop a sustained release tablets, the need for the technique, the formation of solid dispersion with polymeric materials that can potentially enhance the dissolution rate and extent of drug absorption was considered in this study. The 1:1, 1:4, and 1:5 solid dispersions were prepared by spray drying method using PVP K30, ethanol and methylene chloride. The dissolution test was carried out at in phosphate buffer solution at 37℃ in 100 rpm. solid dispersed drugs were examined using differential scanning calorimetry and scanning electron microscopy, wherein it was found that felodipine is amorphous in the PVP K30 solid dispersion. Felodifine SR tablets were prepared by direct compressing the powder mixture composed of solid dispersed felodipine, lactose, Eudragit and magnesium stearate using a single punch press. In order to develop a sustained-release preparation containing solid dispersed felodipine, a comparative dissolution study was done using commercially existing product as control. The dissolution rate of intact felodipine, solid dispersed felodipine and its physical mixture, respectively, were compared by the dissolution rates for 30 minutes. The dissolution rates of felodipine for 30 minutes from 1:1, 1:4, 1:5 PVP K30 solid dispersion were 70%, 78% and 90%. However, dissolution rate offelodipine from the physical mixture was 5% of drug for 30 minutes. Our developed product Felodipine SR Tablet showed dissolution of 17%, 50% and 89% for 1, 4, and 7 hours. This designed oral delivery system is easy to manufacture, and drug releases behavior is highly reproducible and offers advantages over the existing commercial product. The dissolution rate of felodipine was significantly enhanced. following the formation of solid dispersion. The solid dispersion technique with water-soluble polymer could be used to develop a solid dispersed felodipine SR tablet.

고체분산체에 의한 펠로디핀의 용출율 개선과 서방성 경구제제

길영식,홍석천,유창훈,신현종,김종성,Gil, Young-Sig,Hong, Seok-Cheon,Yu, Chang-Hun,Shin, Hyun-Jong,Kim, Jong-Sung 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.3

To improve the solubility of poorly water-soluble drug and to develop a sustained release tablets, the need for the technique, the formation of solid dispersion with polymeric materials that can potentially enhance the dissolution rate and extent of drug absorption was considered in this study. The 1:1, 1:4, and 1:5 solid dispersions were prepared by spray drying method using PVP K30, ethanol and methylene chloride. The dissolution test was carried out at in phosphate buffer solution at $37^{\circ}C$ in 100 rpm. Solid dispersed drugs were examined using differential scanning calorimetry and scanning electron microscopy, wherein it was found that felodipine is amorphous in the PVP K30 solid dispersion. Felodifine SR tablets were prepared by direct compressing the powder mixture composed of solid dispersed felodipine, lactose, Eudragit and magnesium stearate using a single punch press. In order to develop a sustained-release preparation containing solid dispersed felodipine, a comparative dissolution study was done using commercially existing product as control. The dissolution rate of intact felodipine, solid dispersed felodipine and its physical mixture, respectively, were compared by the dissolution rates for 30 minutes. The dissolution rates of felodipine for 30 minutes from 1:1, 1:4, 1:5 PVP K30 solid dispersion were 70%, 78% and 90%. However, dissolution rate offelodipine from the physical mixture was 5% of drug for 30 minutes. Our developed product Felodipine SR Tablet showed dissolution of 17%, 50% and 89% for 1, 4, and 7 hours. This designed oral delivery system is easy to manufacture, and drug releases behavior is highly reproducible and offers advantages over the existing commercial product. The dissolution rate of felodipine was significantly enhanced, following the formation of solid dispersion. The solid dispersion technique with water-soluble polymer could be used to develop a solid dispersed felodipine SR tablet.

PVP 첨가에 의해 제조된 올메사탄 메독소밀 고체분산체의 방출패턴 연구

오승창(Seung-Chang Oh),이천중(Cheon Jung Lee),이현구(Hyun Gu Lee),박진영(Jin Young Park),정현기(Hyun Ki Jeong),김영래(Young-Lae Kim),임동권(Dong-Kwon Lim),이동원(Dongwon Lee),강길선(Gilson Khang) 한국고분자학회 2015 폴리머 Vol.39 No.1

올메사탄은 BCS 2단계에 해당하는 약물로 물에 잘 녹지 않는 난용성 약물이다. 이런 약물이 낮은 생체이용률과 제형을 설계하는 과정에서 어려움을 주는 원인이 된다. 본 연구에서는 올메사탄을 분무건조법 및 회전용매증발법을 이용해 고체분산체를 제조하여 제법에 따른 난용성약물의 용출률을 확인하였다. 수용성 고분자로 PVP를 사용하여 약물과 고분자의 비율별로 고체분산체를 제조하였다. SEM을 이용하여 고체분산체의 형태학적인 특성을 분석하였고, 고체분산체의 결정학적 성질은 XRD와 DSC를 통하여 확인하였다. 또한 FTIR을 통해 화학적인 변화를 확인하고, 생체 외 용출거동 실험을 통하여 변화된 용출률을 확인하였다. 제조된 고체분산체는 pH 1.2에서 용출을 확인하였으며, 올메텍과 용출률을 비교하였으며, 분무건조를 통해 약물의 용출률을 향상시킬 수 있다는 것을 확인할 수 있다. Olmesartan affiliated to biopharmaceutics classification system class 2 is a poorly water soluble drug. For this reason, olmesartan showed a low bioavailability and a lot of difficulties in the process of designing the pharmaceutical formulation. We prepared the solid dispersions of olmesartan. We confirmed the dissolution rate of drug which was prepared by manufacturing. The pharmaceutical formulation of solid dispersions was designed by using PVP as water soluble polymer. We analyzed morphological feature of solid dispersion by employing a scanning electron microscope. Then, the crystalline property of solid dispersion was confirmed through X-ray diffraction and differential scanning calorimeter. Also, the chemical change of solid dispersion was confirmed by the Fourier transform infrared spectroscopy. In vitro dissolution test was used to analyze the dissolution rate of solid dispersion. The prepared solid dissolution olmesartan confirmed the dissolution rate in the pH 1.2. It was compared with olmetec and improved dissolution rate through solid dispersion.

프란루카스트와 폴리(N-비닐피롤리돈)의 나노고체분산체에 의한 용출률 개선

박상욱 ( Sang Wook Park ),이준희 ( Jun Hee Lee ),김대성 ( Dae Sung Kim ),김원 ( Won Kim ),박종학 ( Jong Hak Park ),안식일 ( Sik Il Ahn ),김윤태 ( Yun Tae Kim ),신형식 ( Hyung Shik Shin ),이종문 ( John M. Rhee ),강길선 ( Gilson Kh 한국조직공학·재생의학회 2008 조직공학과 재생의학 Vol.5 No.4

To overcome solubility of poorly water soluble drugs, we prepared solid dispersions containing nanoparticles of water insoluble pranlukast using spray dryer. These solid dispersions formulated to improve the dissolution of pranlukast. PVP-K30 used as a water soluble carrier for the solid dispersion and poloxamer used as a surfactant. Characterization of pranlukast solid dispersion analyzed by scanning electron microscope(SEM), differential scanning calorimeter(DSC) and particle size analyzer. SEM and DSC were found that pranlukast is amorphous in solid dispersions. Particle size analyzer was used to investigate size of pranlukast in solid dispersions. The in vitro dissolution rate of pranlukast solid dispersion was significantly higher than the conventional drugs(Onon(R) and Prakanon (R)), as 11~33 folds. This studies illustrated the potential use of solid dispersion for the delivery of poorly water soluble drug, such as pranlukast by the oral route.

다양한 친수성 고분자를 이용한 삼중층 정제의 니페디핀 서방화 및 특성분석

이천중(Cheon Jung Lee),하현정(Hyun Jung Ha),김수영(Su Young Kim),박진영(Jin Young Park),장나금(Na Keum Jang),송정은(Jeong Eun Song),강길선(Gilson Khang) 한국고분자학회 2015 폴리머 Vol.39 No.5

니페디핀은 고혈압 치료제로 쓰이는 약물로 난용성이기 때문에 용출률의 개선이 필요한 약물이다. 또한 반감기가 1.5~2시간 정도로 짧기 때문에 약물방출을 서방화시킬 필요성이 있다. 본 연구에서는 니페디핀의 약물 방출을 조절하기 위하여 다중층 정제를 통한 24시간 방출제어를 목표로 하였다. 다중층 정제는 윗층과 아래층 그리고 가운데층의 세층으로 이루어지며 윗층과 아래층은 gel-forming 고분자를 이용하여 방출조절을 시도하였다. 가운데 층은 니페디핀의 용출률 향상을 위해 니페디핀과 폴리비닐프롤리돈 K30의 고체분산체를 제조하여 사용하였다. 고체분산체 분석을 위한 SEM, XRD 그리고 DSC분석을 실시하였으며, 인공장액(pH 6.8)에서 생체 외 용출거동을 24시간동안 실시하였다. 실험 결과, 여러 종류의 친수성 고분자 종류 중 하이드록시프로필 메틸셀룰로스 K15M을 사용한 니페디핀 삼중층 제형이 가장 좋은 서방형 패턴과 용출률을 확인할 수 있었다. 이를 통해 니페디핀의 서방화 가능성을 확인할 수 있었다. Nifedipine is mainly used for treatment of antianginal (especially in Prinzmetal’s angina) and antihypertensive. However, it is needed to improve the dissolution rate because it is poorly water-soluble drug. Nifedipine needs the sustained release formulation due to its short half-life of 1.5~2 h. Therefore, the purpose of this study is to control the burst release of nifedipine through the multi-layer as three layers formulation for 24 h. Upper and bottom layers consisted of gel-forming polymers as release controlling agent, and the middle layer was prepared by nifedipin-PVP K30 solid dispersion. The prepared solid dispersion was analyzed by SEM, XRD and DSC. The prepared multi-layer tablet was characterized by swelling assays. The release behavior of nifedipine from the multi-layer tablet was confirmed through in vitro assay (pH 6.8). It was confirmed that the nifedipine three-layered tablet using hydroxypropylmethyl cellulose (HPMC) K15M showed the best of sustained pattern and dissolution behavior.

The effect of solvent and polymer ratio in Acyclovir Solid Dispersion using Spray Drying Technique

서민정,김유빈,박하향,조영호,이계원 한국공업화학회 2018 한국공업화학회 연구논문 초록집 Vol.2018 No.1

아세클로페낙 고체분산체의 특성 및 용출를 개선

김윤태(Yun Tae Kim),박현진(Hyun Jin Park),이영현(Young Hyun Lee),홍희경(Hee Kyung Hong),엄신(Shin Eom),김용기(Yong Ki Kim),이온용(Eun Yong Lee),최명규(Myoung Gyu Choi),이재준(Jae Jun Lee),조용백(Yong Baik Cho),강길선(Gil Son Khang) 한국고분자학회 2009 폴리머 Vol.33 No.6