2-HP-β-시클로덱스트린과 메글루민을 이용한 란소프라졸의 포접화합물 제조 및 평가

이정우,김정수,장혜진,이계원,지웅길,Lee, Jung-Woo,Kim, Jung-Su,Chang, Hye-Jin,Lee, Gye-Won,Jee, Ung-Kil 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.4

To enhance the solubility and stability of lansoprazole (LAN), new proton pump inhibitor, we were prepared various molar ratio of inclusion complex with $2-hydroxypropyl-{\beta}-cyclodextrin$ (HPCD) and organic alkali agent, meglumine (MEG). Inclusion complex formation of LAN with HPCD was investigated by Differential Scanning Calorimetry and X-ray diffractometry. The aqueous solubilities of inclusion complexes, and the stabilities of 1:4 and 1:5 inclusion complexes in aqueous solutions containing different concentrations of MEG were examined. The stability of 1:5 LAN-HPCD inclusion complex containing MEG, which was equaled to amount of LAN, was performed in 0.9% NaCl and 5% dextrose solution. The formation of inclusion complex of LAN with HPCD was $A_L$ type and the molar ratio of complex was 1:1. The stability constant was $41.557\;M^{-1}$. As molar ratio of LAN to HPCD was increased, solubility of inclusion complex was increased. 1:5 LAN-HPCD inclusion complex was more stable than 1:4 LAN-HPCD inclusion complex. And as contained MEG amount in LAN solution was increased, stability of 1:4 and 1:5 LAN-HPCD inclusion complexes was improved. Also stability of 1:5 LAN-HPCD-MEG inclusion complex in 0.9% NaCl solution and 5% dextrose solution was similar to it in water at room temperature, but it was unstable at $40^{\circ}C$.

2-HP-β-시클로덱스트린과 메글루민을 이용한 란소프라졸의 포접화합물 제조 및 평가

이정우,김정수,장혜진,이계원,지웅길 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.4

To enhance the solubility and stability of lansoprazole (LAN), new proton pump inhibitor, we were prepared various molar ratio of inclusion complex with 2-hydroxypropyl-(3-cyclodextrin (HPCD) and organic alkali agent, meglumine (MEG). Inclusion complex formation of LAN with HPCD was investigated by Differential Scanning Calorimetry and X-ray diffractometry. The aqueous solubilities of inclusion complexes, and the stabilities of 1:4 and 1:5 inclusion complexes in aqueous solutions containing different concentrations of MEG were examined. The stability of 1:5 LAN-HPCD inclusion complex containing MEG, which was equaled to amount of LAN, was performed in 0.9% NaCl and 5% dextrose solution. The formation of inclusion complex of LAN with HPCD was AL type and the molar ratio of complex was 1:1. The stability constant was 41.557 M^(-1). As molar ratio of LAN to HPCD was increased, solubility of inclusion complex was increased. 1:5 LAN-HPCD inclusion complex was more stable than 1:4 LAN-HPCD inclusion complex. And as contained MEG amount in LAN solution was increased, stability of 1:4 and 1:5 LAN-HPCD inclusion complexes was improved. Also stability of 1:5 LAN-HPCD-MEG inclusion complex in 0.9% NaCl solution and 5% dextrose solution was similar to it in water at room temperature, but it was unstable at 40℃.

헤스페레틴(Hesperetin)과 사이클로덱스트린(Cyclodextrin) 포접 복합체의 항산화, 항염증, 항균 활성

최성숙,이경애 한국응용과학기술학회 2023 한국응용과학기술학회지 Vol.40 No.5

Hesperetin(HT) is a potent antioxidant flavonoid aglycone derived from hesperidin(HD). The antioxidant, anti-inflammatory, and antimicrobial activities of HT and its cyclodextrin(CD) inclusion complexes were compared in vitro. HT was prepared by enzymatic hydrolysis of HD, and HT/CD complexes were prepared using β-cyclodextrin(β-CD) and hydroxypropyl-βcyclodextrin(HP-β-CD) by solvent co-evaporation method. The solubility of the HT/HP-β-CD inclusion complex increased 93.5-fold compared to HT, and the solubility of HT/β-CD increased 22.5-fold. The HT/HP-β-CD inclusion complex showed a similar effect as HT on radical scavenging activity in antioxidant assays, whereas the HT/β-CD inclusion complex showed slightly lower activity than HT. Cytotoxicity was low in the following order; HT/HP-β-CD, HT/β-CD, and HT in murine macrophage RAW264.7 cells. Treatment with HT and HT/CD inclusion complexes reduced the levels of inflammatory mediators such as nitric oxide(NO), tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in the cells. HT and HT/HP-β-CD inclusion complex were more effective than HT/β-CD inclusion complex at relatively low concentrations. Inhibitory effects were tested on skin-pathogenic bacteria, Staphylococcus aureus and Pseudomonas aeruginosa, and they showed an antimicrobial effect on S. aureus in the order of HT = HT/HP-β-CD > HT/β-CD, but they did not show any significant inhibitory effect on P. aeruginosa. In conclusion, HT, the aglycone form of HD, and its CD inclusion complexes showed various biological activities. HT/HP-β-CD inclusion complex, which is the highly soluble form of HT, showed relatively higher activity compared to HT/β-CD inclusion complex.

Improvement of photostability and dissolution profile of isradipine using inclusion complex

박준범,이건희,강지원,전익성,김정미,김기범,강진영 한국약제학회 2013 Journal of Pharmaceutical Investigation Vol.43 No.1

Inclusion complexes using b-cyclodextrin were manufactured by solvent evaporation method. Then, sustained release (SR) hydroxypropylmethylcellulose (HPMC)matrix tablets containing inclusion complex were prepared via direct compression. Isradipine was chosen as a model drug due to its low solubility, photo-instability and short elimination half-life. The physicochemical properties of the inclusion complexes were examined using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The solubility test and dissolution behaviours were also investigated. Based on the solubility experiments, a 1:2 molar ratio (isradipine:b-Cyclodextrin)was best and chosen to prepare inclusion complexes. In addition, the crystal structure of isradipine was converted to an amorphous structure, as confirmed by Fourier transform infrared spectroscopy (FT-IR) and DSC. The photostability of isradipine in the inclusion complex was more stable than pure isradipine after 4 days radiation. By using hypromellose as the hydrophilic sustained release material, the dissolution rate was retarded during 24 h. A combined method of inclusion complex and SR technology showed increased and sustained release profile above that of Dynacirc SR Cap. 5 mg.

Preparation and Characterization of Inclusion Complex between β-Cyclodextrin and Polylactic Acid

Song Ya Nan,Zhou Yu Fang,Zhen Wei Jun 한국고분자학회 2015 폴리머 Vol.39 No.2

The inclusion complexes (ICs) between polylactic acid (PLA) and β-cyclodextrin (CD) were prepared by coprecipitation method in this work. The orthogonal experiments were designed to investigate the influence of different factors on the formation of inclusion complexes. The results suggested that the optimum scheme of inclusion compounds could be obtained when the feeding ratio of CD to PLA (wt%) was 20:1, stirring speed was 6 kr/min and the stirring time was 30 min. The structures and properties of the inclusion complexes were characterized by <SUP>1</SUP>H NMR, FTIR, DSC, FT-Raman, XRD and TGA. The DSC results demonstrated that the crystallization behavior of the inclusion complexes nearly disappeared. It was found that β-CD-PLA inclusion complex had a better thermal stability compared with the neat PLA. The model of the inclusion complexes was proposed on the basis of XRD, <SUP>1</SUP>H NMR and DSC results.

Morphology and Chemistry of Oxide Inclusions After Al and Ti Complex Deoxidation

선민기,이해건,정인호 대한금속·재료학회 2008 METALS AND MATERIALS International Vol.14 No.6

The morphology and chemistry of oxide inclusions after various Al and Ti complex deoxidation sequences were investigated at 1600℃. Depending on the addition sequence of Al and Ti deoxidants and the holding time, the morphology and the chemistry were changed. In particular, when Ti was added prior to Al, spherical Al₂O₃ oxide inclusions with hollow holes were frequently observed, which is reported for the first time. On the other hand, when Al was added prior to Ti, Al₂O₃ inclusion formed. When Al and Ti were added simultaneously, Al-Ti-O oxide inclusion formed in the beginning and was transformed to Al₂O₃ inclusion. Based on the experimental results, the formation mechanism of the oxide inclusions after Al-Ti deoxidation was proposed. The nozzle clogging of Ti bearing Al killed steel was also discussed based on the experimental results. The morphology and chemistry of oxide inclusions after various Al and Ti complex deoxidation sequences were investigated at 1600℃. Depending on the addition sequence of Al and Ti deoxidants and the holding time, the morphology and the chemistry were changed. In particular, when Ti was added prior to Al, spherical Al₂O₃ oxide inclusions with hollow holes were frequently observed, which is reported for the first time. On the other hand, when Al was added prior to Ti, Al₂O₃ inclusion formed. When Al and Ti were added simultaneously, Al-Ti-O oxide inclusion formed in the beginning and was transformed to Al₂O₃ inclusion. Based on the experimental results, the formation mechanism of the oxide inclusions after Al-Ti deoxidation was proposed. The nozzle clogging of Ti bearing Al killed steel was also discussed based on the experimental results.

Characterization of an inclusion complex of, 7-dehydrocholesterol and cyclodextrin

Sung Ho Kim,Jae Young Youn,Kyung Min Kim,Ki Choon Kang,Hyeong Bae Pyo,Sang Jong Lee 한국공업화학회 2010 Journal of Industrial and Engineering Chemistry Vol.16 No.1

7-Dehydrocholesterol (7-DHC) plays an important role in the biosynthesis of vitamin D. It is virtually insoluble in water, in which its manipulation is difficult, but the problems may be alleviated by cyclodextrin inclusion. Cyclodextrins are known to form inclusion complex with many kinds of hydrophobic compounds because theirmolecular structure generates a hydrophilic exterior surface and a hydrophobic cavity interior. The purpose of this study was to characterize inclusion complex of 7-dehydrocholesterol with cyclodextrin (hydroxypropyl-b-cyclodextrin, HPbCD). The inclusion complex showed good solubility in contrast to physical mixture. The inclusion efficiency determined by HPLC analysis was 83.72%. Additionally, the inclusion complex was characterized by UV–vis spectrophotometry, Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). These results demonstrated that 7-dehydrocholesterol with hydroxypropyl-b-cyclodextrin formed an inclusion complex.

In Vitro and In Vivo Studies on the Complexes of Vinpocetine with $Hydroxypropyl-{\beta}-cyclodextrin$

Fan, Xiaowen,Peng, Ying,Yang, Xingang,Wang, Chao,Pan, Weisan,Nie, Shufang 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.8

The purpose of this study was to evaluate complexes of vinpocetine (VIN), a poorly water-soluble base type drug, with $Hydroxypropyl-{\beta}-cyclodextrin$ ($HP-{\beta}-CD$) in aqueous environment and in solid state, with or without citric acid (CA) as an acidifier of the complexation medium. The apparent stability constant ($K_c$) calculated by phase solubility was 282 $M^{-1}$ and the complexation in solution was structurally characterized by $^1H-NMR$ which showed VIN was likely to fit into the cyclodextrin cavity with its phenyl ring and ethyl ester bond. Solid complexes of VIN and $HP-{\beta}-CD$ were prepared by kneading (KE), co-evaporating (CE) and freeze-drying (FD) methods. Physical mixtures were prepared for comparison. The study in the solid state included the differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and infrared absorption spectroscopy (IR). From these analyses, CE and FD products were found in amorphous state, allowing to the conclusion of strong evidences of inclusion complex formation However, the dissolution test showed that only $VIN/HP-{\beta}-CD+CA$ complexes by CE and FD method could provide satisfying dissolution behavior (rapid, complete and lasting) when compared to that of $VIN/HP-{\beta}-CD$ complexes. Interestingly, the addition of CA in inclusion complexes could significantly decrease the amount of $HP-{\beta}-CD$ needed to solubilize the same amount of VIN and thereby reducing the formulation bulk. Furthermore, in-vivo study revealed that the bioavailability of VIN after oral administration to rabbits (n=6) was significantly improved by $VIN/HP-{\beta}-CD+CA$ inclusion complex.

In Vitro and In Vivo Studies on the Complexes of Vinpocetine with Hydroxypropyl-β-cyclodextrin

Shufang Nie,Xiaowen Fan,Ying Peng,Xingang Yang,Chao Wang,Weisan Pan 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.8

The purpose of this study was to evaluate complexes of vinpocetine (VIN), a poorly water-soluble base type drug, with hydroxypropyl-β-cyclodextrin (HP-β-CD) in aqueous environment and in solid state, with or without citric acid (CA) as an acidifier of the complexation medium. The apparent stability constant (Kc) calculated by phase solubility was 282 M-1 and the complexation in solution was structurally characterized by 1H-NMR which showed VIN was likely to fit into the cyclodextrin cavity with its phenyl ring and ethyl ester bond. Solid complexes of VIN and HP-β-CD were prepared by kneading (KE), co-evaporating (CE) and freeze-drying (FD) methods. Physical mixtures were prepared for comparison. The study in the solid state included the differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and infrared absorption spectroscopy (IR). From these analyses, CE and FD products were found in amorphous state, allowing to the conclusion of strong evidences of inclusion complex formation. However, the dissolution test showed that only VIN/HP-β-CD+CA complexes by CE and FD method could provide satisfying dissolution behavior (rapid, complete and lasting) when compared to that of VIN/HP-β-CD complexes. Interestingly, the addition of CA in inclusion complexes could significantly decrease the amount of HP-β-CD needed to solubilize the same amount of VIN and thereby reducing the formulation bulk. Furthermore, in-vivo study revealed that the bioavailability of VIN after oral administration to rabbits (n=6) was significantly improved by VIN/HP-β-CD+CA inclusion complex.

Electrochemical and Raman Spectroscopy Analysis for Dand L-Tryptophan-Cyclodextrin Inclusion Complexes

Yu-Ra Jeong,So-Ra Lee,Pyeong-Soo Son,Seong-Ho Choi 한국유화학회 2015 한국응용과학기술학회지 Vol.32 No.3

An enantioselective recognition of D- and L-tryptophan (Trp)-b-cyclodextrin (CD) inclusion complex was performed using electrochemical and FT-Raman spectroscopic analysis. From the electrochemical analysis, the selectivity coefficient (KDL) of b-CD inclusion complexes was found higher than that of the D- and L-Trp in phosphate buffered saline (PBS, pH=7.0) solution. The percentage of enantioselectivity (I%ee) for peak current of D-Trp-b-CD inclusion complexes was observed higher than that of L-Trp-b-CD inclusion complexes in PBS solution. From Raman spectroscopy, chemical shift difference (D, cm-1) for the C=C stretch, ring vibration, and ring breathing of D-Try-b-CD inclusion complex were observed higher than that of L-Trp-b-CD inclusion complex. The electrochemical and Raman spectroscopic analyses were found very useful for chiral detection of racemic amino acid in the presence of b-CD.