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Solid Dispersion as a Strategy to Improve Drug Bioavailability
박준형,전명관,조훈,최후균,Park, Jun-Hyung,Chun, Myung-Kwan,Cho, Hoon,Choi, Hoo-Kyun The Korean Society for Biotechnology and Bioengine 2011 KSBB Journal Vol.15 No.6
Solid dispersion is one of well-established pharmaceutical techniques to improve the dissolution and consequent bioavailability of poorly water soluble drugs. It is defined as a dispersion of drug in an inert carrier matrix. Solid dispersions can be classified into three generations according to the carrier used in the system. First and second generations consist of crystalline and amorphous substances, respectively. Third generation carriers are surfactant, mixture of polymer and surfactants, and mixture of polymers. Solid dispersions can be generallyprepared by melting method and solvent method. While melting method requires high temperature to melt carrier and dissolve drug, solvent method utilizes solvent to dissolve the components. The improvement in dissolution through solid dispersions is attributed to reduction in drug particle size, improvement in wettability, and/or formation of amorphous state. The primary characteristics of solid dispersions, the presenceof drug in amorphous state, could be determined by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and fourier-transformed infrared spectroscopy (FTIR). In spite of the significant improvement in dissolution by solid dispersion technique, some drawbacks have limited the commercial application of solid dispersions. Thus, further studies should be conducted in a direction to improve the congeniality to commercialization.
히드록시프로필 - 베타 - 시클로덱스트린과 피록시캄 및 테녹시캄 간의 복합체 형성
김주현(Ju Hyun Kim),최후균(Hoo Kyun Choi) 한국약제학회 2000 Journal of Pharmaceutical Investigation Vol.30 No.1
One of the methods to increase the solubility of a drug is to use complexation with a cyclodextrin. Due to the hydrophobic nature of the interior cavity of the cyclodextrin, it has been known that undissociated lipophilic drugs can be included within the cyclodextrin by hydrophobic interaction. Recently, inclusion of hydrophilic or dissociated form of a drug has been investigated. In this study, the synergism of pH and complexation with hydroxypropyl-β-cyclodextrin (HP β CD) to increase the solubility of two oxicam derivatives was investigated. In addition, the effect of partition coefficient of dissociated and undissociated form of the drug on the extent of complexation with HP β CD was studied. The solubility was measured by equilibrium solubility method. The solubility of tenoxicam and piroxicam increased exponentially with an increase in solution pH above the pKa of the drug in the presence and absence of HP β CD. The solubility of the drugs increased linearly as a function of HP β CD concentration at fixed pH. Although the stability constant of ionized species is less than that of the unionized species, the concentration of the ionized drug complex is greater than that of the unionized drug complex due to higher concentration of ionized species at pH 7.3.
케토프로펜의 피부투과도를 증진시키는 다양한 용매의 작용기전
조영주(Young Joo Cho),최후균(Hoo Kyun Choi) 한국약제학회 1998 Journal of Pharmaceutical Investigation Vol.28 No.3
N/A The effect of various vehicles on the permeation of a model drug, ketoprofen in solution formulation was evaluated using a flow-through diffusion cell system at 37℃. To investigate the mechanism of permeation rate enhancement, the effects of pretreatment with various vehicles on the permeation of the drug were evaluated using 5 ㎎/㎖ solution and saturated solution. The order of permeation rate of ketoprofen across hairless mouse skin after pretreatment with various vehicles was similar to the case where the vehicles and the drug were coadministered except ethanol and oleic acid. The results indicate that the mechanism of enhancement can be direct action of the vehicles on the barrier property of the skin and/or carrier mechanism.
고시 수재 의약품 중 피라세탐 정 및 브롬화수소산페노테롤 정의 용출시험법 개발
김은정,이진하,박찬호,손경희,김인규,김동섭,사홍기,최후균,Kim, Eun-Jung,Lee, Jin-Ha,Park, Chan-Ho,Sohn, Kyung-Hee,Kim, In-Kyu,Kim, Dong-Sup,Sah, Hong-Kee,Choi, Hoo-Kyun 대한약학회 2011 약학회지 Vol.55 No.4
Although the dissolution test can serve as an effective tool for quality control and predictor of in vivo performance, there are a number of drugs with no established dissolution specifications in Korean Pharmaceutical Codex (KPC). Among those commercially available, Piracetam Tablets and Fenoterol hydrobromide Tablets were selected to develop the dissolution testing method. The dissolution condition was determined based on the "Guidelines on Specifications of Dissolution tests for Oral dosage forms" of Korea Food & Drug Administration (KFDA). The dissolution test for Piracetam Tablets was carried out under sink condition with distilled water as dissolution medium, paddle rotation speed at 50 rpm and medium volume of 900 ml. More than 80% of its label claim was released within 30 min. In case of Fenoterol hydrobromide Tablets, distilled water was also found to be suitable to ensure sink condition. The rotation speed of 50 rpm and 900 ml of dissolution medium were used to evaluate the dissolution profile. The dissolution rate of fenoterol hydrobromide was over 90% in 15 min. The HPLC analysis methods were validated in terms of accuracy, precision, specificity, linearity, quantitation limit and range. The results suggested that the analytical methods used are simple and suitable to measure the dissolution rate of piracetam and fenoterol hydrobromide. Therefore, the analysis methods could be utilized in setting dissolution specifications of Piracetam Tablets and Fenoterol hydrobromide Tablets in the revised version of KPC.
Solid Dispersion as a Strategy to Improve Drug Bioavailability
Jun-Hyung Park(박준형),Myung-Kwan Chun(전명관),Hoon Cho(조훈),Hoo-Kyun Choi(최후균) 한국생물공학회 2011 KSBB Journal Vol.26 No.4
Solid dispersion is one of well-established pharmaceutical techniques to improve the dissolution and consequent bioavailability of poorly water soluble drugs. It is defined as a dispersion of drug in an inert carrier matrix. Solid dispersions can be classified into three generations according to the carrier used in the system. First and second generations consist of crystalline and amorphous substances, respectively. Third generation carriers are surfactant, mixture of polymer and surfactants, and mixture of polymers. Solid dispersions can be generallyprepared by melting method and solvent method. While melting method requires high temperature to melt carrier and dissolve drug, solvent method utilizes solvent to dissolve the components. The improvement in dissolution through solid dispersions is attributed to reduction in drug particle size, improvement in wettability, and/or formation of amorphous state. The primary characteristics of solid dispersions, the presenceof drug in amorphous state, could be determined by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and fourier-transformed infrared spectroscopy (FTIR). In spite of the significant improvement in dissolution by solid dispersion technique, some drawbacks have limited the commercial application of solid dispersions. Thus, further studies should be conducted in a direction to improve the congeniality to commercialization.