Polymorphism of Cefotaxime sodium

Sohn, Young-Taek,Park, Sun-Hee 덕성여자대학교 약학연구소 2005 藥學論文誌 Vol.16 No.1

Three crystal forms of cefotaxime sodium have been isolated by recrystallization and characterized by powder X-ray diffractometry, differential scanning calorimetry, and thermogravimetric analysis. The dissolution patterns of three crystal forms of cefotaxime sodium were studied in water at 37±0.5℃, 90rpm for 180 minutes. Three crystal forms of cefotaxime sodium showed difference in dissolution rate and solubility. After storage of two months at 52% RH (saturated solution of Na_(2)Cr_(2)O_(2).2H_(2)O / 20℃), all crystal forms showed no transformation.

디클로페낙 소디움의 용출에 미치는 결정형의 영향

손영택,정수경 德成女子大學校 藥學硏究所 2002 藥學論文誌 Vol.13 No.1

Diclofenac sodium used in this study is the NSAID (Nonsteroidal anti-inflammatory drug) and it was investigated whether polymorphism of diclofenac sodium exists. A new modification of diclofenac sodium was obtained by the recrystallization method from different organic solvents and characterized by UV spectrophotometry, DSC, X-ray crystallography and TGA. It is confirmed that one is the modification on the market and the other is the methanol solvate. The dissolution patterns of these two modifications on the market and the other is the methanol solvate. The dissolution patterns of these two modifications were also checked in distilled water at 37℃ and showed a significant difference in the dissolution rate. The dissolution rate of Mod. 2 is lower than that of the modification on the market. After 70-day storage at 0%, 52% humidity, Mod. 2 was changed to Mod. 1.

세팔렉신의 결정다형에 관한 연구

손영택,김소영 德成女子大學校 藥學硏究所 1996 藥學論文誌 Vol.7 No.1

Four crystal forms of cephalexin were prepared and characterized by DSC and TGA. Their dissolution patterns were checked and it was confirmed that the theory of Higuchi was not always correct. All crystal forms were stable.

수용성 고분자물질-단백질 접합체의 합성 및 응용

용철순,손영택 영남대학교 약품개발연구소 1994 영남대학교 약품개발연구소 연구업적집 Vol.4 No.-

Since the advent of recombinant DNA technology coupled with other biotechnology a variety of therapeutically effective proteins and peptides have been extensively invesitigated and many of them are now on clinical trial. They, however, suffer from some problems such as immunogenicity, antigenicity, instability and short half-life in circulation due to their proteinous natures. These draw-backs can be overcome successfully by conjugating proteins and peptides with hydrophilic polymers such as polyethylene glycol (PEG), albumin or dextran. The resulting soluble conjugates showed reduced antigenicity and immunogenicity, increased circulatory half-life, enhanced stability against proteolytic degradation. Comparing with the unmodified proteins and peptides, the therapeutic potential of conjugates is greatly enhanced. Clinical applications of these conjugates have shown promising results for the future use.

치료경험이 있는 A형 혈우병 환자에서 그린모노^�의 약동학 및 안전성 : 전향적 다기관 공동 임상시험

윤휘중,이순용,황태주,손영택 德成女子大學校 藥學硏究所 2001 藥學論文誌 Vol.12 No.1

배 경 : 최근 국내에서 사용 가능해 진 단클론항체를 이용한 고순도의 제 8응고인자 그린모노^R에 대하여, 제품의 약동학적 측면을 관찰하고, 급성 이상반응 발생 측면의 안전성을 관찰하고자 하였다. 방 법 : 과거 응고인자 치료경험이 있는 제 8응고인자치 5% 미만의 A 형 혈우병 환자를 대상으로, 그린모노를 체중 1kg당 50units 정맥주사한 후 약물역동학적 분석을 시행하였다. 약물 투여 후 48시간까지 이상반응을 관찰하고, 약물투여 전 및 48시간 까지 이상반응을 관찰하고, 약물투여 전 및 48시간 후에 일반혈액 검사, 혈액생화학검사, 요검사 등을 측정하여 비교하였다. 제8응고인자 억제인자를 Bethesda assay를 이용하여 투여 전 및 투여 3~7일 후 검사하였다. 결 과 : 15명의 환자중 연구를 완료한 13명의 자료를 분석하였다. Recovery rate는 99±22%(범위, 71~ 136%) 였으며, 2-compartment model을 이용한 beta phase의 반감기는 15.7±6.6시간(범위, 9.7~35.9시간)이었다. 그린모노^ R 투여후 의미있는 이상반응은 없었으며, 검사성적의 의미있는 변화도 발견할 수 없었다. 제8응고인자 억제인자는 시험약 투여 전후 모두 0.6 BU 미만으로 유지되었다. 결 론: 그린모노^R는 약동학적으로 유효하고, 급성이상 반응이 없어, 임상 이용에유용하리라 생각한다.

Characterization of Physicochemical Properties of Ferulic Acid

Sohn, Young-Taek,Oh, Jin-Hee The Pharmaceutical Society of Korea 2003 Archives of Pharmacal Research Vol.26 No.12

Ferulic acid (3-methoxy, 4-hydroxy cinnamic acid) is a flavoid component possessing antioxidant property. The compound is currently under development as a new drug candidate for the treatment of the dementia. The objective of this preformulation study was to determine the physicochemical properties of ferulic acid. The n-octanol to water partition coefficients of ferulic acid were 0.375 and 0.489 at the pHs of 3 and 10, respectively. Accelerated stability study for ferulic acid indicated that the t 90 value for the drug was estimated to be 459 days at $25^{\circ}C$. Ferulic acid was also found to be unstable under the relative humidity of more than 76%, probably because of the hygroscopic nature of the drug. In order to study compatibility of ferulic acid with typical excipients, potential change in differential scanning calorimetry spectrum was studied in 1: 1 binary mixtures of ferulic acid and typical pharmaceutical excipients (e.g., Aerosil, Avicel, CMC, Eudragit, lactose, PEG, PVP, starch and talc). Avicel, CMC, PVP and starch were found to be incompatible with ferulic acid, indicating the addition of these excipients may complicate the manufacturing of the formulation for the drug. Particle size distribution of ferulic acid powder was in the size range of 10-190 $\mu$m with the mean particle size of 61 $\mu$m. The flowability of ferulic acid was apparently inadequate, indicating the granulation may be necessary for the processing of the drug to solid dosage forms. Two polymorphic forms were obtained by recrystallization from various solvents used in formulation. New polymorphic form of ferulic acid, Form II, was obtained by recrystallization from 1,4-dioxane. The equilibrium solubility for Form I was approximately twice of that for Form II. The dissolution rate of Form II was higher than that of Form I in the early phase (<6 min). Therefore, these physicochemical information has to be taken in the consideration for the formulation of ferulic acid.

Polymorphism of Clarithromycin

Sohn, Young-Taek,Rhee, Jae-Keol,Im, Weon-Bin The Pharmaceutical Society of Korea 2000 Archives of Pharmacal Research Vol.23 No.4

It is well recognized that physicochemical properties of drugs are affected by the type of polymorphic crystalline form of drugs. Clarithromycin is known to exist in at least three polymorphic crystalline forms. Since conventional means to obtain the most thermodynamically stable form (Form II) for the antibiotics is known to be associated with a low purity of the stable form, we developed a novel method to improve the purity of the crystalline form by a modification of the preparation process. The new method involved a simple recrystallization of clarithromycin in solvents having 5-12 carbon atoms (e.g., hexane and heptane) or ethers with 4-10 carbon atoms (e.g., isopropyl ether) and, thus, less likely to be associated with the problem in purity of resulting crystal. Differential scanning calorimetry and powder X-ray diffraction were used to compare the crystalline form of the resultant powder with Form IIcrystal prepared by the conventional method. The crystal prepared by the new method was identical to Form IIcrystal of the conventional method as evidenced by the lack of the exothermic peak near 11$0^{\circ}C$ in differential calorimetry scan, indicating that Form IIcrystal could be readily prepared by the new process. Therefore, these data indicated that the improvement in the purity of the Form IIcrystal for clarithromycin as well as a significant cost reduction is likely by the novel method.

Characterization of the Physicochemical Properties of KR-31378

Sohn, Young-Taek,Park, Bo-Ye The Pharmaceutical Society of Korea 2003 Archives of Pharmacal Research Vol.26 No.7

KR-31378 is a new drug candidate intended for the use in the prevention of ischemia-reperfusion damage. The objective of this preformulation study was to determine the physicochemical properties of KR-31378. The n-octanol to water partition coefficients of KR-31378 were 0.0504 at pH 3 and 0.8874 at pH 10. Accelerated stability of KR-31378 in solution and solid state was studied at 5, 40, $60^{\circ}C$. The stability testing indicated that the t90 for the drug in solid was estimated to be 2 years and 128.6 days at $25^{\circ}C$, while the that in aquesou solution was 68.6 days at $25^{\circ}C$. The KR-31378 was also found to be unstable under the relative humidity of 76%, probably because of the hygroscopic nature of the drug. In order to study compatibility of KR-31378 with typical excipients, potential change in differential scanning calorimetry spectrum was studied in 1:1 binary mixtures of KR-31378 and Aerosil, Avicel, Eudragit, lactose, PEG, talc, CMC, PVP, starch. As a result, CMC, PVP, and starch were found to be incompatible with KR-31378, indicating the addition of these excipients may complicate the manufacturing of the formulation for the drug. Particle size distribution of KR-31378 powder was in the size range of 9-93 $\mu$ m with the mean particle size of 37.9 $\mu$ m. The flowability of KR-31378 was apparently inadequate, indicating the granulation may be necessary for the processing of the drug to solid dosage forms. Crystallization of the drug with a number of organic solvents did not lead a crystalline polymorphism. In addition, dissolution of the drug from the powder was adequately rapid at $37^{\circ}C$ in water.

Crystal Form of Cefprozil

Sohn, Young-Taek,Chon, Hye-Rin 덕성여자대학교 약학연구소 2006 藥學論文誌 Vol.17 No.-

Several crystal forms of Cefprozil have been isolated by recrystallization and they are characterized by powder X-ray diffractometry, differential scanning calorimetry, and thermogravimetric analysis. It is proved that only one crystal form of Cefprozil exists.

Study on Polymorphism of Cefotaxime Sodium, Cephradine, and Ceftriaxone Sodium

Young Taek Sohn,Sun Hee Park 大韓藥學會 2003 大韓藥學會 總會 및 學術大會 Vol.2003 No.2