• Journal of Pharmaceutical Investigation
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• v.30 no.4
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• pp.289-293
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• 2000

Three polymorphic modifications and one amorphous form were prepared by recrystallization under various conditions and characterized by DSC and X-ray crystallography. At $37{\pm}0.5^{\circ}C$, the polymorphic modifications showed significant differences in the dissolution rate. The dissolution rate of Mod. 4, amorphous form, was faster than that of other polymorphic modifications. When all modifications were stored at 52% RH, 95% RH, and in silica gel desiccator, amorphous form was transformed at 95% humidity condition.

• Journal of Pharmaceutical Investigation
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• v.32 no.2
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• pp.81-85
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• 2002

Three polymorphic modifications of CKD-602, water soluble derivative of camptothecin, were obtained by the recrystallization from different organic solvents and characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and X-ray powder diffraction (XRPD). The major endothermic peaks of the DSC curve of Form 1, Form 2 and Form 3 was shown at $268.71^{\circ}C$, $247.83^{\circ}C$, $244.76^{\circ}C$, respectively. Form 2 was elucidated to be an acetic acid solvate and Form 3 was elucidated to be a methanol solvate. The dissolution patterns of these three modifications were also checked in distilled water at $37{\pm}0.5^{\circ}C$, for 30 minutes. The polymorphic modifications showed differences in the dissolution rate. The dissolution rate of Form 1 was faster than that of other polymorphic modifications. When stored at different relative humidity over the period of 3 months, all of the polymorphic modifications did not undergo transformation.

• Journal of Pharmaceutical Investigation
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• v.20 no.1
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• pp.35-42
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• 1990

A new form of sulfabenzamide was characterized using X-ray diffraction patterns and differential scanning calorimetry. Solubility studies demonstrated that, of the sulfabenzamide polymorphs, the new form was more soluble than form I. Compression of the new form at compression force of 1000 $kg/cm{^2}$ didn't induce polymorphic change in the crystal. Similar patterns were also produced through grinding. The effects of some diluents on the polymorphic transformation from the new form into form I by grinding and compression were also studied. Three diluents, $Avicel^{\circledR}$, lactose and starch showed no influence on the polymorphic transformation. The new form seemed to be more suitable for the pharmaceutical preparation.

• Journal of Pharmaceutical Investigation
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• v.30 no.3
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• pp.201-205
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• 2000

Three new polymorphic modifications were prepared by recrystallization under various conditions and characterized by DSC and X-ray crystallography. In pH 4.0 buffer at $37{\pm}0.5^{\circ}C$, the polymorphic modifications showed significant differences in the dissolution rate. The dissolution rate of Mod. 4, amorphous form, was faster than that of marketed cefaclor (Mod. 1). When all modifications were stored at 52% RH, 95% RH and in silica gel desiccator, any polymorphic transformation was not observed.

• Journal of Pharmaceutical Investigation
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• v.28 no.2
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• pp.81-85
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• 1998

Three polymorphic modifications and two pseudopolymorphic modifications of cefotaxime sodium were obtained by crystallization from different organic solvents. The isolated crystal forms were characterized by UV spectrophotometry, DSC, TGA and X-ray crystallography. Crystal forms of cefotaxime sodium were also compared by dissolution rate. The dissolution rate of form 1 was the highest, followed by form 2, form 4, form 6, form 5 and form 3. Among these polymorphic modifications the dissolution rate of form 3 and form 5 was much slower than that of cefotaxime sodium on the market. All forms showed no change after 2-month storage test in the silica gel desiccator. But after the storage of 2-month at 95% relative humidity condition, all forms were deliquesced by hygroscopic property except form 1 that showed the highest dissolution rate. At 52% relative humidity condition, form 1, form 2 and form 6 had no evidence of phase transformation, but form 3, form 4 and form 5 were also deliquesced.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.228.2-229
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• 2003

Investigation of polymorphism has become a requirement in the pharmaceutical industry because the physical properties and bioavailabilities of crystalline drugs depend on their polymorphic form. Two polymorphic modifications and one pseudopolymorphic modification of cefotaxime sodium were prepared by recrystallization in organic solvents under variable conditions. Four polymorphic modifications of cephardine were prepared by recrystallization. Three polymorphic modifications and one pseudopolymorphic modification of ceftriaxone sodium were prepared by recrystallization. (omitted)

• Archives of Pharmacal Research
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• v.7 no.1
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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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• v.27 no.3
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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.

• Archives of Pharmacal Research
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• v.23 no.4
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• pp.381-384
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• 2000

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.

• Journal of Pharmaceutical Investigation
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• v.40 no.spc
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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.