• Archives of Pharmacal Research
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• 제7권1호
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• pp.47-52
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• 1984

Four polymorphic forms (I, II, III and IV) of hydrochlorothiazide have been characterized on the basis of x-ray diffractometry and differential thermal analysis. Form I was obtained by crystallization from N, N-dimethylformamide and Form II was crystallized from hot methanol. Form III was precipitated from sodium hydroxide aqueous solution by treatment with hydrochloric acid and Form IV was crystallized from 50% methanol. The metastable form I was a most stable form among four polymorphs, which was stable more than ten months at room temperature. The thermodynamic parameters such as heat of solution, enthalpy, entropy, free energy difference and transition temperature were determined by the measurement of intrinsic dissolution rate. The transition temperature and the heat of transition between the metastable Form I an Form II were determined to be $299.15^{\circ}$K and 5.03 Kcal/mole, respectively and free energy difference ($\delta$ F) was 302. 13 cal/mole. Diuretic action of these four polymorphic forms was also evaluated by monitoring the difference in urinary excretion of sodium, potassium and magnesium in rats.

• Journal of Pharmaceutical Investigation
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• 제40권spc호
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• pp.9-17
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• 2010

Polymorphism has been recognized to be a critical issue throughout the drug product development process. Most of solid phase drugs have polymorphism, which has generated a great deal of interest and the field has been evolving rapidly. Preferably, thermodynamically most stable form of a drug substance is selected to obtain consistent bioavailability over its shelf life and various storage conditions. Moreover, it has the lowest potential for conversion from one polymorphic form to another. However, metastable or amorphous forms may be used intentionally to induce faster dissolution rate for rapid drug absorption and higher efficacy. For pharmaceutical industry, polymorphism is one of the key activities in form selection process together with salt selection. This article introduces the main features in the investigation of solid form selection especially polymorphic behavior with thermodynamic backgrounds, physicochemical properties with solubility, dissolution, and mechanical properties, and characterization techniques for proper analysis. The final form can be recommended based on the physicochemical and biopharmaceutical properties and by the processability, scalability and safety considerations. Pharmaceutical scientists especially in charge of formulation need to be well aware of the above issues to assure product quality.

• 한국분말재료학회지
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• 제12권1호
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• pp.36-42
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• 2005

Four different mechanical alloying(MA) processes were employed to fabricate very fine intermetallic compound $Al_3Zr$ particles dispersed Al composite materials(MMC) with Al-4at.%Zr composition. Phase transformations including phase stability during MA and heat treatment processes were investigated. Part of Zr atoms were dissolved into Al matrix and part of them reacted with hydrogen produced by decomposition of PCA(methanol) to form hydride $ZrH_2$ during first MA process. These $ZrH_2$ hydrides disappeared when alloy powders were heat treated at $500^{\circC}$. Stable $Al_3Zr$ dispersoids with $DO_23$ structure were formed by heat treating the mechanically alloyed powders at $400^{\circC}$. On the other hand, metastable $Al_3Zr$dispersoids with $L1_2$ structure were formed during first MA of powers with Al-25at.%Zr composition. These metastable $Al_3Zr$ dispersoids transformed to stable $Al_3Zr$ with $DO_23$ structure when heat treated above $450^{\circC}$.

• 한국분말재료학회지
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• 제26권2호
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• pp.146-155
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• 2019

Rare earth magnets are the strongest type of permanent magnets and are integral to the high tech industry, particularly in clean energies, such as electric vehicle motors and wind turbine generators. However, the cost of rare earth materials and the imbalance in supply and demand still remain big problems to solve for permanent magnet related industries. Thus, a magnet with abundant elements and moderate magnetic performance is required to replace rare-earth magnets. Recently, $a^{{\prime}{\prime}}-Fe_{16}N_2$ has attracted considerable attention as a promising candidate for next-generation non-rare-earth permanent magnets due to its gigantic magnetization (3.23 T). Also, metastable $a^{{\prime}{\prime}}-Fe_{16}N_2$ exhibits high tetragonality (c/a = 1.1) by interstitial introduction of N atoms, leading to a high magnetocrystalline anisotropy constant ($K_1=1.0MJ/m^3$). In addition, Fe has a large amount of reserves on the Earth compared to other magnetic materials, leading to low cost of raw materials and manufacturing for industrial production. In this paper, we review the synthetic methods of metastable $a^{{\prime}{\prime}}-Fe_{16}N_2$ with film, powder and bulk form and discuss the approaches to enhance magnetocrystalline anisotropy of $a^{{\prime}{\prime}}-Fe_{16}N_2$. Future research prospects are also offered with patent trends observed thus far.

• Journal of Pharmaceutical Investigation
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• 제28권2호
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• pp.115-119
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• 1998

Five polymorphic modifications of Cephradin were prepared by recrystallization from organic solvents. The isolated crystal forms were characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and X-ray crystallography powder diffractometry. Modificaition 1 was the most stable form and decomposed at $201.3^{\circ}C$. Modification 3 and 4 were metastable. The dissolution of modification 3 and 4 was faster than that of marketed form.

• Journal of Pharmaceutical Investigation
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• 제27권3호
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• pp.233-239
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• 1997

Glibenclamide is a second generation sulfonylurea that is orally active as a hypoglycemic drug. It exists as a crystalline powder which is sparingly soluble in water. It was investigated that the potential of glibenclamide to exhibit polymorphism. Three polymorphic modifications (form 1, form 2 and form 3) and three pseudopolymorphic modifications (form 4, form 5 and form 6) were obtained by crystallization from different organic solvents. The isolated crystal forms were characterized by differential scanning calorimetry(DSC), thermogravimetric analysis(TGA) and X-ray crystallography powder diffraction studies. Form 1 was the most stable and melt at $175.4^{\circ}C$. Form 2 was metastable and melt at $151.0^{\circ}C$. Form 3 was a new polymorphic modification because it was different from form 1 and form 2 in X-ray crystallography powder diffraction data. Form 4 was a 1 : 7(toluene : glibenclamide) toluene solvate; form 5 was a 1 : 5(toluene : glibenclamide) toluene solvate; form 6 was a 3 : 8(pentanol : glibenclamide) pentanol solvate. All forms were stable in 3-month storage under 0% or 100% humidity condition. The dissolution rate of form 4 was highest; those of form 2, form 3, form 1, form 5 and form 6 followed.

• 한국세라믹학회지
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• 제39권3호
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• pp.315-320
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• 2002

저농도로 희석된 HF 수용액(6 wt%)을 사용하여 $Al(OH)_3$의 표면을 F/Al의 몰비 0.15에서 처리하고, 처리 전후 표면특성을 관찰하였다. 반응계의 온도 및 pH 변화로부터 $Al(OH)_3$에 대한 HF의 표면반응은 HF와 접촉한 $Al(OH)_3$ 표면부에서 metastable한 ${\alpha}$형의 불화알루미늄$({\alpha}-AlF_3{\cdot}3H_2O)$이 안정한 ${\beta}$형의 불화알루미늄$({\beta}-AlF_3{\cdot}3H_2O)$으로 전이되는 과정으로 진행되며, 다량의 발열을 수반하면서 반응계의 온도상승을 유발하였다. 이러한 ${\beta}-AlF_3{\cdot}3H_2O$의 생성은 표면처리된 분말의 FT-IR 및 X-선 회절분석결과를 통해 확인되었다. ${\beta}-AlF_3{\cdot}3H_2O$의 morphology와 분포상태를 SEM을 통해 관찰한 결과 $Al(OH)_3$ 표면에 $1{\mu}m$ 이하의 미세분말 형태로 피복층을 형성하며 균일하게 분포된 것으로 확인되었다. HF로 처리된 시료의 표면 백색도는 미처리에 비해 약 6.6% 증가되었으며, 이는 $Al(OH)_3$보다 높은 백색도를 지닌 ${\beta}-AlF_3{\cdot}3H_2O$ 피복 효과 때문인 것으로 나타났다.

• 한국진공학회:학술대회논문집
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• 한국진공학회 1999년도 제17회 학술발표회 논문개요집
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• pp.29-29
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• 1999

The synthesis of layered structures on the nanometer scale has become essential for continued improvements in the operation of various electronic and magnetic devices. Abrupt metal-metal interfaces are desired for applications ranging from metallization in semiconductor devices to fabrication of magnetoresistive tunnel junctions for read heads on magnetic disk drives. In particular, characterizing the interface structure between various transition metals (TM) and aluminum is desirable. We have used the techniques of MeV ion backscattering and channeling (HEIS), x-ray photoemission (ZPS), x-ray photoelectron diffraction(XPD), low-energy ion scattering (LEIS), and low-energy electron diffraction(LEED), together with computer simulations using embedded atom potentials, to study solid-solid interface structure for thin films of Ni, Fe, Co, Pd, Ti, and Ag on Al(001), Al(110) and Al(111) surfaces. Considerations of lattice matching, surface energies, or compound formation energies alone do not adequately predict our result, We find that those metals with metallic radii smaller than Al(e.g. Ni, Fe, Co, Pd) tend to form alloys at the TM-Al interface, while those atoms with larger atomic radii(e.g. Ti, Ag) form epitaxial overlayers. Thus we are led to consider models in which the strain energy associated with alloy formation becomes a kinetic barrier to alloying. Furthermore, we observe the formation of metastable fcc Ti up to a critical thickness of 5 monolayers on Al(001) and Al(110). For Ag films we observe arbitrarily thick epitaxial growth exceeding 30 monolayers with some Al alloying at the interface, possible driven by interface strain relief. Typical examples of these interface structures will be discussed.

• 한국전기전자재료학회:학술대회논문집
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• 한국전기전자재료학회 2001년도 추계학술대회 논문집 Vol.14 No.1
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• pp.3-6
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• 2001

In common globular proteins, the native form is in its most stable state. However, the native form of inhibitory serpins (serine protease inhibitors) and some viral membrane fusion proteins is in a metastable state. Metastability in these proteins is critical to their biological functions. Our previous studies revealed that unusual interactions, such as side-chain overpacking, buried polar groups, surface hydrophobic pockets, and internal cavities are the structural basis of the native metastability. To understand the mechanism by which these structural defects regulate protein functions, cavity-filling mutations of a 1-antitrypsin, a prototype serpin, were characterized. Increasing conformational stability is correlated with decreasing inhibitory activity. Moreover, the activity loss appears to correlate with the decrease in the rate of the conformational switch during complex formation with a target protease. We also increased the stability of a 1-antitrypsin greatly via combining various stabilizing single amino acid substitutions that were distributed throughout the molecule. The results showed that a substantial increase of stability, over 13 kcal/mol, affected the inhibitory activity with a correlation of 11% activity loss per kcal/mol. The results strongly suggest that the native metastability of proteins is indeed a structural design that regulates protein functions and that the native strain of a 1-antitrypsin distributed throughout the molecule regulates the inhibitory function in a concerted manner.

• E2M - 전기 전자와 첨단 소재
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• 제14권12호
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• pp.3-6
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• 2001

In common globular proteins, the native form is n its most stable state. However, the native form of inhibitory serpins (serine protease inhibitors) and some viral membrane fusion proteins is in a metastable state. Metastability in these proteins is critical to their biological functions. Our previous studies revealed that unusual interactions, such as side-chain overpacking, buried polar groups, surface hydrophobic pockets, ad internal cavities are the structural basis of the native metastability. To understand the mechanism by which these structural defects regulate protein functions, cavity-filling mutations of $\alpha$1-antitrypsin, a prototype serpin, were characterized. Increasing conformational stability is correlated with decreasing inhibitory activity. Moreover, the activity loss appears to correlate with the decrease in the rate of the conformational switch during complex formation with a target protease. We also increased the stability of $\alpha$1-antitrypsin greatly via combining various stabilizing single amino acid substitutions that were distributed throughout the molecule. The results showed that a substantial increase of stability, over 13 kcal/mol, affected the inhibitory activity with a correlation of 11% activity loss per kcal/mol. The results strongly suggest that the native metastability of proteins is indeed a structural design that regulates protein functions and that the native strain of $\alpha$1-antitrypsin distributed throughout the molecule regulates the inhibitory function in a concerted manner.