Release Behavior of Telmisartan/Amlodipine Combination Drug According to Polymer Type

빈수영,최정민,김필윤,김원경,Alessio Bucciarelli,송정은,강길선 한국고분자학회 2021 Macromolecular Research Vol.29 No.3

Patients at risk for hypertension with comorbidities such as diabetes and metabolic syndrome often require two or more antihypertensive drugs to lower their blood pressure. Telmisartan and amlodipine are widely known drugs to treat hypertension. However, telmisartan suffer of poor solubility in water that makes necessary to increase its dosage to reach a sufficient therapeutic concentration. In this study, a solid dispersion containing a water-soluble polymer was prepared to make the absorption rate of telmisartan similar to that of amlodipine, a water soluble drug. As water-soluble polymers, polyvinylpyrrolidone K30, polyethylene glycol 6000, and poloxamer 407 were used. The encapsulation of the solid dispersion was analyzed by differential scanning calorimetry, Xray diffraction, and high-performance liquid chromatography. The reduced flowability of the solid dispersion was improved by a wet granulation. Scanning Electron Microscopy was used to study the morphology and the flowability was verified by measuring the angle of repose, bulk density, and tap density, and expressed by Hausner ratio and Carr index. The release behavior was confirmed by dissolution test and high-performance liquid chromatography. As result we proved that telmisartan a higher release rate when encapsulated with PVP K30. Finally, we designed a drug formulation in which amlodipine and telmisartan could be absorbed at a similar rate.

Improvement of Medication Adherence and Controlled Drug Release by Optimized Acetaminophen Formulation

빈수영,최정민,이영훈,김필윤,김원경,조훈휘,이지은,Alessio Bucciarelli,이대훈,송정은,강길선 한국고분자학회 2021 Macromolecular Research Vol.29 No.5

Acetaminophen (paracetamol, APAP) is a major component of Tylenol, Penzal Q, and Panpyrin, and is the most commonly used antipyretic analgesic in children. The conventional oral drug delivery systems of APAP are pills and tablets. However alternative drug delivery methods are desirable in case of pediatric or geriatric patients, especially for drugs like APAP that must be taken in large doses at once. Another requirement for a good drug delivery system is the rapid dissolution to ensure a rapid therapeutic action as pain reliever. In this study Acetaminophen (paracetamol, APAP) was encapsulated in a water-soluble polymer. After the preparation of the solid dispersion by encapsulating acetaminophen in polyvinylpyrrolidone, the resultant granules were used in three formulations: tablets, chewable tablets, and oral dissolving films (ODF). Solid dispersions and prepared formulations were evaluated by Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffractometer (XRD), and universal tensile machine (UTM), and the release behavior was compared. As a result, it was confirmed that the oral dissolving films can be taken easily because it has the advantages of both tablet and liquid dosage form accurate dosage, easy administration, easy swallowing, and fast bioavailability. Furthermore, the drug absorption rate can be effectively increased by changing the formulation.

습식과립을 이용한 시나칼세트염산염의 방출거동

이지은(Ji Eun Lee),빈수영(Suyoung Been),최정민(Jeongmin Choi),조훈휘(Hunhwi Cho),김남영(Namyeong Kim),송정은(Jeong Eun Song),강길선(Gilson Khang) 한국고분자학회 2021 폴리머 Vol.45 No.1

만성신부전환자의 이차성 부갑상선 기능 항진 치료제로 알려진 시나칼세트염산염은 BCS class Ⅳ의 특성을 갖는 난용성 약물이다. 난용성 개선을 위하여, 본 연구에서는 수용성 고분자와 난용성 약물 시나칼세트염산염으로 습식과립물을 제조한 후, 첨가제를 비율별로 혼합하여 정제를 설계하였다. FTIR을 이용하여 습식과립 공정에서 일어나는 화학적 변화를 평가하였고, 정상적으로 과립이 형성되었는지 확인하기 위하여 DSC와 XRD를 진행하였다. 이 후 정제가 제대로 설계되었는지 확인하기 위하여 인공위액(pH1.2)에서 방출 실험을 진행하였으며 HPLC를 통하여 측정하였다. 결과적으로 수용성 고분자를 이용한 습식과립물의 제조가 난용성 약물인 시나칼세트염산염의 방출에 효과적인 것을 확인할 수 있었다. Cinacalcet hydrochloride, known as a treatment for a secondary hyperparathyroidism in a chronic renal failure, is a poorly soluble drug with the properties of BCS class IV. To improve poor solubility, in this study, after preparing a wet granule of soluble polymer and poorly soluble drug cinacalcet hydrochloride, tablets were designed by mixing additives by proportion. Chemical changes occurring in the wet granulation process were evaluated using FTIR, and DSC and XRD were performed to confirm that the granules were formed as designed. After this, the release was tested through HPLC in an artificial gastric acid (pH1.2) to confirm that the tablet was properly designed. As a result, it was confirmed that the formation of the wet granules using a soluble polymer was effective for the release of cinacalcet hydrochloride, a poorly soluble drug.

Impact of Agarose Hydrogels as Cell Vehicles for Neo Retinal Pigment Epithelium Formation: In Vitro Study

이대훈,이주화,편윤창,신명은,신은영,빈수영,송정은,Claudio Migliaresi,Antonella Motta,강길선 한국고분자학회 2022 Macromolecular Research Vol.30 No.12

Retinal pigment epithelium (RPE) which plays a key role of the visual function is destroyed by retinal diseases, which are affected to visual impairment or blindness. Agarose (Agr) prepared from Marine red algae is a thermo-reversible biopolymer and applied to variable tissue regeneration study due to its biocompatibility. However, Agr-based RPE tissue engineering study hasn’t been reported. The purpose of this study is verification regarding applicability of Agr hydrogels for RPE regeneration. Agr hydrogels with different amounts of Agr were prepared, there were no significant differences of the results regarding chemical composition with the amounts of Agr. On the other hands, increasing the amounts of Agr in hydrogels were affected to pore size, degradation, swelling, compressive strength and porosity due to the differences of physical cross-linking. From in vitro test, RPE cells were well attached on the surface of Agr hydrogels regardless of the amounts of Agr. Furthermore, cell proliferation and RPE-specific gene expression were highly influenced with high amounts of Agr in the hydrogels. It was considered that these results in this study was related to stiffness difference of hydrogels. Agr hydrogels could be promising scaffolds for RPE tissue regeneration progressed by the tissue engineering technique.

Eudragit RS/RL을 이용한 고체분산에 의한 티카그렐러 서방형 제형 설계

문병관(Byungkwan Moon),이영훈(Younghun Lee),김승재(Seung Jae Kim),빈수영(Suyoung Been),김나은(Na Eun Kim),이성원(Seong Won Lee),박선재(Sunjae Park),송정은(Jeong Eun Song),강길선(Gilson Khang) 한국고분자학회 2022 폴리머 Vol.46 No.6

티카그렐러는 급성관상동맥증후군 환자의 뇌졸중과 심장마비를 예방하는 약물로서 용해도와 생체막 투과성이 낮은 생물약제학적 분류체계 IV에 속하는 약물이다. 이에 생체이용률을 높이기 위해서는 약물가용화 과정이 필수적이다. 이를 위해 친수성이고 pH 비의존적 고분자 Eudragit RL PO, Eudragit RS PO을 사용해 분무건조법으로 습식과립공정을 통해 고체 분산체를 제조하였다. 약물이 무정형으로 고분자 매트릭스에 분산되었는지 X-ray diffractometer, differential scanning calorimetry를 통해 결정성 및 포접을 확인하였고, Fourier transform infrared spectroscopy을 통해 화학적 변화를 확인하였다. 최종적으로, 용출시험을 통해 약물의 방출제어가 잘 이루어졌는지 확인하여, 복용 회수를 줄이고 환자의 복약 순응도를 높인 제형으로 개발 가능함을 확인하였다. Ticagrelor is a drug that prevents stroke and heart attack in patients with acute coronary syndrome and belongs to the biopharmaceutical classification system IV with low solubility and permeability. Therefore, in order to increase the bioavailability, the drug solubilization process is essential. To this end, a solid dispersion was produced through a wet granulation process by a spray-drying method using hydrophilic and pH-independent polymers Eudragit RL PO and Eudragit RS PO. Crystallinity and saturation were confirmed through X-ray diffractometer and differential scanning calorimetry whether the drug was dispersed in a polymer matrix in an amorphous form, and a chemical change was confirmed through Fourier transform infrared spectroscopy. Finally, it was confirmed that the release control of the drug was well performed through the dissolution test, and it was possible to develop a formulation that reduced the number of doses and improved the patients compliance with the dose.