Young-Taek Sohn

Crystal forms of naproxen

The objective of this work was to investigate the existence of polymorphs and pseudopolymorphs of naproxen and the transformation of crystal forms. Four crystal forms of naproxen have been isolated by recrystallization and characterized by differential scanning calorimetry, powder X-ray diffractometry and thermogravimetric analysis. The differential scanning calorimetry and powder X-ray diffractometry patterns of the four crystal forms were different respectively. In the dissolution studies in pH 6.8 ± 0.05 buffer equilibrated at 37 ± 0.5°C, the solubility of four crystal forms was similar (within the error range). After storage of 1 month at 0% RH (silica gel, 20°C), 52% RH (saturated solution of Na2Cr2O7.2H2O/20°C) and 95% RH (saturated solution of Na2HPO4/20°C), Form 2 and Form 4 were transformed to Form 1, but Form 3 and Form 1 were not transformed and they were shown to have a good physical stability at room temperature for 1 month.

Polymorphism of Clarithromycin

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 II crystal prepared by the conventional method. The crystal prepared by the new method was identical to Form II crystal of the conventional method as evidenced by the lack of the exothermic peak near 110°C in differential calorimetry scan, indicating that Form II crystal could be readily prepared by the new process. Therefore, these data indicated that the improvement in the purity of the Form II crystal for clarithromycin as well as a significant cost reduction is likely by the novel method.

Crystal Forms of Atorvastatin

The objective of this work was to investigate the existence of new polymorphs and pseudopolymorphs of atorvastatin and the transformation of crystal forms. Three crystal forms of atorvastatin have been isolated by recrystallization and characterized by powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TG). The PXRD and DSC patterns of the three crystal forms were different respectively and it was confirmed that Form 3 is a new crystal form. After storage of 2 years at room temperature, this new crystal form was not transformed and it was shown to have a good physical stability.

Polymorphism of doxazosin mesylate

Nine polymorphic modifications of doxazosin mesylate have been obtained by recrystallization in organic solvents under variable conditions. Different polymorphs of doxazosin mesylate were characterized by powder X-ray crystallography diffractometry (PXRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TG). Transformation of Form 1 and Form 2 was not occurred in three relative humidities (0%, 51%, and 99%) at 20±0.5 for 30 days.

Effect of crystal form on in vivo topical anti-inflammatory activity of corticosteroids.

The aim of this study was to gain information on the effects of the crystal form of corticosteroids on the topical anti-inflammatory activity. Two different crystal forms, Form A and Form B, of the drugs of prednicarbate, hydrocortisone, betamethasone 17-valerate, prednisolone, and methyl prednisolone were prepared and their topical anti-inflammatory activities were measured using arachidonic acid induced ear edema assay in mice. Two crystal forms of the drugs showed differences in anti-inflammatory activity. Among the drugs examined, Form B of prednicarbate and betamethasone 17-valerate showed significantly more potent anti-inflammatory activities as compared to their Form A.

Crystal forms of ketorolac

Four crystal forms of ketorolac have been obtained by recrystallization in organic solvents under variable conditions. Different ketorolac polymorphs and pseudopolymorph were characterized by X-ray powder diffraction crystallography (XRD), Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). In the dissolution studies in water at 37+−0.5°C, four crystal forms showed different patterns. The solubility of Form I were the highest. The solubility decreased in rank order: Form I > Form II > Form III > Form IV. Form land Form III were shown to have a good physical stability at room temperature for 60 days. However, Form II is converted to Form III and Form IV is converted to Form I after 60 days storage. Therefore, these observations indicate that crystalline polymorphism for ketorolac is readily inter-convertible and the relationship may have to taken into consideration in the formulation of the drug.

Solid State of CG-400549, A Novel FabI Inhibitor: Characterization, Dissolution, Transformation

The polymorphic and pseudopolymorphic forms of CG-400549, a novel FabI inhibitor with potent in vivo activity were prepared and characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD) and thermogravimetric analysis (TG). Seven crystal forms of CG-400549, one anhydrate and six solvates, have been isolated by recrystallization and the DSC and PXRD patterns of the seven crystal forms of CG-400549 were different respectively. The dissolution patterns of these seven crystal forms of CG-400549 were studied and they showed significant differences in the dissolution rate. After storage of 1 month at 0% RH (silica gel, 20°C), 52% RH (saturated solution of Na2Cr2O72H2O/20°C) and 95% RH (saturated solution of Na2HPO4/20°C), all crystal forms were not transformed.

Crystal forms of SK-3530

The objective of this work was to investigate the existence of polymorphs of SK-3530 and the transformation of crystal forms. Two crystal forms of SK-3530 have been isolated by recrystallization and characterized by differential scanning calorimetry, powder X-ray diffractometry and thermogravimetric analysis. The differential scanning calorimetry and powder X-ray diffractometry patterns of two crystal forms were different respectively. After storage of 1 month at 0% RH (silica gel, 20°C), 52% RH (saturated solution of Na2Cr2O7·2H2O/20°C) and 95% RH (saturated solution of Na2HPO4/20°C), Form 2 was not transformed to Form 1 and two forms were shown to have a good physical stability at room temperature for 1 month. In the dissolution studies in pH 6.8 buffer at 37 ± 0.5°C, the dissolution rate of Form 2 was significantly higher than that of Form 1 under 30 min.

Solid state of a new PDE-5 inhibitor DA-8159: Characterization, dissolution, transformation

The polymorphic forms of a new PDE-5 inhibitor DA-8159 were prepared and characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD) and thermogravimetric analysis (TG). Two crystal forms and one amorphous form of DA-8159 have been isolated by recrystallization and characterized by DSC, TG and PXRD. From the TG data it was confirmed that two crystal forms are neither solvates nor hydrates. The PXRD patterns of the two crystal forms were different. In the dissolution studies in simulated intestinal fluid at 37 ± 0.5°C, the solubility decreased in the order of amorphous form > Form 1 > Form 2. After storage of 60 days, Form 1 was transformed to Form 2. Form 2 was not transformed. The amorphous form was transformed to Form 2 at 52% R.H. and 95% R.H., but it did not transform at 0% R.H.

Crystal Form of Cefuroxime axetil

Two crystal forms of cefuroxime axetil were obtained by the recrystallization from different organic solvents and characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD). It was confirmed that two crystal forms are identical. The dissolution patterns of these two forms were also checked in 0.07 N HCl at , 100 rpm for 180 minutes. The transformation during storage was also studied.