효소 소화성 하이드로겔 정제의 팽윤 및 프록시필린 방출 특성

심창구(Chang Koo Shim),이영미(Young Mee Lee),여소현(So Hyeon Yeo) 대한약학회 1992 약학회지 Vol.36 No.3

Although oral route is the most convenient route for drug administration, the short and variable transit of drug through GI tract restricts the sustained drug absorption after oral administration. Thus, for sustained absorption of drugs, it is desirable to prolong the GI transit time by retaining the dosage forms in the stomach. In this study, the enzyme-digestible swelling hydrogel was synthesized by heating the mixed solution of N-vinyl-2-pyrrolidone[monomerl, acrylated albumin[crosslinking agent] and proxyphylline[drug] at 65oC for 10 hours in the cylindrical test tube. The resultant hydrogel tablet (diameter; 0.77cm, thickness; 0.47cm) was designed to swell in the gastric fluid after oral administration to such a size that passing through the pylorus could be inhibited during the drug release. After releasing drug, the hydrogel was expected to be degraded by pepsin, an enzyme in the stomach, and eventually solubilized. Actually, the hydrogel synthesized in the study swelled to a size larger than the diameter of the pylorus (1.3 +/- 0.7cm) and slowly digested in the presence of pepsin. Drug release from the hydrogel was prolonged up to about 12 hours. The swelling kinetics was dependent on albumin acrylation time, drug content and gel thickness. Particularly the gel thickness was the most important factor that influences on drug release. By adjusting these factors, the albumin-crosslinked hydrogel was expected to be retained in the stomach for up to 60 hours and used as a potential platform of drugs for long-term GI absorption.

제제설계의 최근 진보 : 생체막 투과특성 검색을 통한 제제설계전략

심창구(Shim Chang Koo) 한국약제학회 1999 과학의 달 기념 심포지움 Vol.- No.11

회원 학술보고 : 포스터 발표 / 14. 시판의약품의 제제학적 특성치와 생물학적 동등성과의 상관성 연구

심창구(Chang Koo Shim),나한광(H . K . Na),문화희(H . H . Moon),김동섭(Dong Sup Kim),이영근(Young Keun Lee) 한국약제학회 1992 한국약제학회 총회 및 학술대회 요지집 Vol.- No.22

특별강연 I : 위(胃) 안에서 머물면서 약물을 오랫동안 방출한 후 소화되어 없어질 수 있는 하이드로젤에 관한 연구

심창구(Chang Koo Shim) 한국약제학회 1989 한국약제학회 총회 및 학술대회 요지집 Vol.- No.19

약학사 분과학회의 창립과 비전

심창구(Chang-Koo Shim),김진웅(Jinwoong Kim) 大韓藥學會 2015 약학회지 Vol.59 No.2

The spring convention of the Pharmaceutical Society of Korea (PSK), composed of eight symposia and two special symposia, was held at the K Seoul Hotel on April 17th and 18th in 2014. During the convention, the board meeting of PSK officially approved the birth of Pharmacy History (PH) Division as one of 19 divisions of PSK on April 17th. In the morning of April 18th, an inaugural symposium of PH division was held at the hotel with a theme of "History of Pharmacy in Korea”. In this article, the establishment of PH division, content of the 1st symposium will be described. The future vision of PH division, which will be focused on the study of modern history rather than that of old history, will be described as well. The introduction of modern pharmacy education system to Korea and various events that happened during the establishment of the system may represent issues that should be investigated with the highest priority by the PH division.

피막법에 의한 경구투여용 제어방출제제의 개발 - Ⅲ 테오필린함유 제어방출제제의 제조 및 사람의 타액중 농도로부터의 평가

심창구(Chang - Koo Shim),김종국(Chong - Kook Kim),이민화(Min - Hwa Lee),김신근(shin - Keun Kim) 한국약제학회 1992 Journal of Pharmaceutical Investigation Vol.22 No.3

In order to develop a controlled-release oral drug delivery system (DDS) of theophylline (TP), microporous membrane-coated tablets were prepared and evaluated in vitro and in vivo. Rapidly water-soluble core tablets of TP (300㎎) were prepared by wet granulation and compression technique. Then the core tablets were spray-coated with polyvinylchloride (PVC) in which micronized sucrose particles were dispersed. Effect of formula compositions of coating suspensions on the pharmaceutical characteristics such as membrane strength and dissolution was investigated in vitro. The membranes remained unbroken in pH 1.2 buffer at 37℃ at least for 2 hours after the disintergration test. TP was released from the coated-released tablets at a zero-order rate over 8 hours. The release at pH 1.2 and 4.0 was similar in rate but a little more rapid than that at pH 6.8. The coated tablets were administered to three healthy male volunteers and their saliva profiles of TP were compared with those from the commercial sustained release TP tablets such as Slobid and Asconthin. Saliva TP concentrations from the coated tablets were successfully sustained over 48 hours after the dosing and were comparable to those of the commercial sustained-release tablets. The membrane-coating technique is very simple and does not need any sophisticated equipments. In this respect, the membrane-coated tablets may be superior to the commercial sustained-release tablets and this technique is worth adopting by the pharmaceutical industries.

아르기닌 또는 인산일수소나트륨이 수용액중에서 오메프라졸의 안정성에 미치는 영향 비교

심창구(Chang Koo Shim),한용해(Yong Hae Han),우종수(Jong Soo Woo),이창현(Chang Hyun Lee) 한국약제학회 1993 Journal of Pharmaceutical Investigation Vol.23 No.4

The stability of omeprazole in the aqueous solutions containing arginine or sodium phosphate dibasic(SPD) was examined at 30, 40 and 50℃. Arginine or anhydrous SPD was added to omeprazoie solution (200㎍/㎖ in distilled water) to yield 100㎍/㎖ concentration of each. Then, the solution was kept at 30, 40 or 50℃ for 90 hrs. Aliquots of the solution were withdrawn at specified time intervals and assayed by HPLC for intact omeprazole. The remaining percentage-time curves revealed that omeprazole was degraded rapidly as functions of time and temperature following pseudo first-order kinetics. The rate constant in the SPD solution was much higher than in the arginine solution. In other words. the degradation half-lives of omeprazole at 30℃, for example, was 148 and 76 hr in arginine and SPD solutions respectively. The initial pH of the solution containing 100㎍/㎖ of arginine or SPD was 9.7 or 8.7, respectively. Since omeprazole is more stable as the pH of its solution becomes more alkaline, the longer half-life of omeprazole in arginine solution could be explained by the more alkaline characteristics of arginine than SPD In the solution. The activation energy necessary for the degradation reaction was almost identical in both solutions, indicating similar degradation mechanisms of omeprazole in the solutions. In conclusion, omprazole was more stable in the presence of arginine than of SPD.

감마선 조사법으로 합성한 PVP하이드로겔의 팽윤과 약물방출특성

심창구(Chang Koo Shim),오정숙(Chung Sook Oh),신병철(Byung Chul Shin) 대한약학회 1993 약학회지 Vol.37 No.5

The short and variable transit of drug throught GI tract and the inter-and intra-subject variations of the transit restrict the sustained drug absorption after oral adminstration. These restrictions may be solved by retaining the dosage forms in the stomach. Then the dosage form will act as a platform which releases the drug slowly and makes the GI absorption occur for a long time. In this study, as the platforms, PVP hydrogels were synthesized by chemical and gammar-irradiation method in the cylindrical test tube. The chemical method means the synthesis of the hydrogel by heating the mixed solution of N-vinyl-2-pyrrolidone [monomer], acrylated albumin [crosslinking agent], 2,2''-agobis(2-methylpropionitrile) [initiator] and proxyphylline [drug] at 65oC for 5 hr. The gammar-irradiation method means the synthesis of the hydrogel by irradiation with 60Co gammar-ray of the mixed solution of the monomer, acrylated albumin, and flurbiprofen [drug] at room temperature with total 0.2Mrad for 3 hr. Our intention is to design the hydrogel tablet (diameter : 1.20cm, thickness : 0.60cm) which swells in the gastric fluid after oral administration to such a size that passing through the pylorus could be inhibited during the period of drug release. After releasing drug, the hydrogel should be degraded by the enzymeatic digestion in the stomach, or by hydrolysis and eventually solubilized. Thus, in vitro tests were performed to examine the factors that affect swelling and drug release from the PVP hydrogels. Experimental results show that the hydrogels swell to a size larger than the diameter of the pylorus(1.3 +/- 0.7cm) and the hydrogel prepared by the chemical method is digested by pepsin. But the hydrogel prepared by the gammar-irradiation method was not digested by the pepsin and just collapsed with time. Thus, the swelling of the hydrogel synthesized by gammar-irradiation was independent albumin acrylation time and pepsin concentration. But drug content and radiation dose affected the swelling and drug release kinetics of the hydrogel. Drug release from the hydrigels was prolonged up to about 24 hr. Therefore, it was concluded that by adjusting these factors, the albumin-crosslinked PVP hydrogel synthesized by gammar-irradiation method is expected to be retained in the stomach for up to 60 hr and be a potential platform of drugs for long-term GI absorption.

앰플 및 1회용 주사용기에서의 미립자 혼입에 관한 비교연구

심창구(Chang - Koo Shim),한용해(Yong - Hae Han),권돈선(Don - Sun Kwon) 한국약제학회 1991 Journal of Pharmaceutical Investigation Vol.21 No.3

Particulate is the foreign insoluble material in injectable solution inadvertently present in a given product. Considerable efforts have been made to avoid or minimize particulate contamination by pharmaceutical manufacturers during the production of parenteral products. Particulate contamination of the parenteral products can occur mainly during the opening (cutting) the container immediately before clinical use. In this study, particulate contamination generated during the opening process of ampoules (conventional type, 1-point and color-break ampoules) was compared with that of a prefilled injectable container (prefllled syringe). The particles were examined under a microscope after filtration of the total fluids in the containers. Particles having wide range of size distribution were found from all the ampoules tested. The contamination from the 1-point ampoule and color-break ampoule was much less than from the conventional ampoule. Glass particles generated by cutting the glass-made ampoules seemed a principal source of the particulate contamination. The glass-partiaulte contamination could be improved substantially by replacing the ampoule containers with the prefilled syringe. Prefilled syringe, which can be used without any cutting process, did not generate particulates during the use. Therefore, it was concluded that prefilled syringe is most preferable container for the small volume parenteral (SVP) fluids in terms of particulate contamination.

위내체류를 목적으로 한 알부민 가교 PVP 하이드로겔의 팽윤특성

심창구(Chang - Koo Shim),여소현(So - Hyeon Yeo) 한국약제학회 1993 Journal of Pharmaceutical Investigation Vol.23 No.3

Retaining a drug in the stomach by some means is sometimes necessary to extend the G1 absorption time of the drug more than 6-8 hrs. Hydrogel has often been examined for its feasibility as a dosage form, so called platform, that could be retained in the stomach due to its excellent swelling properties in the gastric fluid. In this study, polyvinylpyrrolidone (PVP) hydrogel crosslinked by albumin or acrylated albumin was synthesized in a tablet form and evaluated for its possibility as the platform. The synthesis of the hydrogel was performed by ^(60)Co γ-ray irradiation of N-vinyl-2-pyrrolidone (monomer) in the presence of a crosslinking agent: aqueous solution of albumin or acrylated albumin. Synthetic conditions such as radiation dose, dose rate and concentration of crosslinking agent were varied in order to optimize the swelling and mechanical properties of the hydrogels. Degree of swelling of albumin-crosslinked PVP (Al-PVP) was highly dependent on radiation dose, dose rate and albumin concentration: it was decreased as they increased. On the other hand, that of acrylated albumin-crosslinked PVP (Acryl-PVP) was almost independent on them except dose rate: it was decreased as the radiation dose rate increased. The compressive strength of the two hydrogels was decreased as the dose rate increased. Digestion of both PVP in artificial gastric fluid containing pepsin was delayed by the γ-ray irradiation. In conclusion, Al-PVP and Acry-PVP with diverse swelling and mechanical properties could be obtained by controlling synthetic conditions, mainly the irradiation dose rate.