Photochemical stability of warfarin potassium in powdered pharmaceutical tablets.

BACKGROUND: Warfarin potassium (Wf) commercial tablets originally formulated for adults are ground before administration to pediatric patients and elderly patients with dysphagia. OBJECTIVE: The present study investigated the effect of tablet grinding on the photostability of four types of commercial Wf tablets and predicted the photostability of the tablet powders by chemometric analysis. METHODS: The photodegradation of Wf content was evaluated by reversed-phase column high-performance liquid chromatography with ultraviolet (HPLC-UV). RESULTS: The bulk Wf powder was relatively photostable, whereas ground Wf tablets underwent substantial photodegradation. The photostability of the ground powders of a brand-name Wf commercial tablet and three generic Wf commercial tablets was quantitatively assessed and compared. In certain cases, the Wf in all the three ground generic tablets was less photostable than in the ground brand-name tablets. After 28 days of light irradiation, the Wf content decreased to 69.79% in the brand-name tablets, while it was 31.90% in some generic tablets. To clarify the factors influencing the relative photostability in various Wf formulations, we analyzed the intermolecular interactions between the active ingredient and the excipients by partial least-squares regression analysis based on photostability screening for each additive. CONCLUSION: The results suggested that the additives light anhydrous silicic acid and povidone adversely affect the stability of Wf tablets. In addition, the light stability of ground tablets was affected considerably by their formulation.

Two polymorphs of 2,5-dichloro-3,6-bis(dibenzylamino)-p-hydroquinone with flexible dibenzylamino groups.

We obtained two conformational polymorphs of 2,5-dichloro-3,6-bis(dibenzylamino)-p-hydroquinone, C34H30Cl2N2O2. Both polymorphs have an inversion centre at the centre of the hydroquinone ring (Z' = 1/2), and there are no significant differences between their bond lengths and angles. The most significant structural difference in the molecular conformations was found in the rotation of the phenyl rings of the two crystallographically independent benzyl groups. The crystal structures of the polymorphs were distinguishable with respect to the arrangement of the hydroquinone rings and the packing motif of the phenyl rings that form part of the benzyl groups. The phenyl groups of one polymorph are arranged in a face-to-edge motif between adjacent molecules, with intermolecular C-H...π interactions, whereas the phenyl rings in the other polymorph form a lamellar stacking pattern with no significant intermolecular interactions. We suggest that this partial conformational difference in the molecular structures leads to the significant structural differences observed in their molecular arrangements.

Gallic Acid, the Active Ingredient of Terminalia bellirica, Enhances Adipocyte Differentiation and Adiponectin Secretion.

Visceral obesity induces the onset of metabolic disorders such as insulin resistance and diabetes mellitus. Adipose tissue is considered as a potential pharmacological target for treating metabolic disorders. The fruit of Terminalia bellirica is extensively used in Ayurvedic medicine to treat patients with diseases such as diabetes mellitus. We previously investigated the effects of a hot water extract of T. bellirica fruit (TB) on obesity and insulin resistance in spontaneously obese type 2 diabetic mice. To determine the active ingredients of TB and their molecular mechanisms, we focused on adipocyte differentiation using mouse 3T3-L1 cells, which are widely used to study adipocyte physiology. We show here that TB enhanced the differentiation of 3T3-L1 cells to mature adipocytes and that one of the active main components was identified as gallic acid. Gallic acid (10-30 µM) enhanced the expression and secretion of adiponectin via adipocyte differentiation and also that of fatty acid binding protein-4, which is the target of peroxisome proliferator-activated receptor gamma (PPARγ), although it does not alter the expression of the upstream genes PPARγ and CCAAT enhancer binding protein alpha. In the PPARγ ligand assay, the binding of gallic acid to PPARγ was undetectable. These findings indicate that gallic acid mediates the therapeutic effects of TB on metabolic disorders by regulating adipocyte differentiation. Therefore, TB shows promise as a candidate for preventing and treating patients with metabolic syndrome.

Effects of ethyl acetate extract of Kaempferia parviflora on brown adipose tissue.

We have previously reported the effects of Kaempferia parviflora (KP), including anti-obesity, preventing various metabolic diseases, and regulating differentiation of white adipose cells. In this study we used Tsumura, Suzuki, Obese Diabetes (TSOD) mice--an animal model of spontaneous obese type II diabetes--and primary brown preadipocytes to examine the effects of the ethyl acetate extract of KP (KPE) on brown adipose tissue, which is one of the energy expenditure organs. TSOD mice were fed with MF mixed with either KPE 0.3 or 1% for 8 weeks. Computed tomography images showed that whitening of brown adipocytes was suppressed in the interscapular tissue of the KPE group. We also examined mRNA expression of uncoupling protein 1 (UCP-1) and ß3-adrenalin receptor (ß3AR) in brown adipose tissue. As a result, mRNA expression of UCP-1 significantly increased in the KPE 1% treatment group, indicating that KPE activated brown adipose tissue. We then evaluated the direct effects of KPE on brown adipocytes using primary brown preadipocytes isolated from interscapular brown adipocytes in ICR mice. Triacylglycerol (TG) accumulation in primary brown preadipocytes was increased by KPE in a dose-dependent manner. Each mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), UCP-1, and ß3AR exhibited an upward trend compared with the control group. Moreover, some polymethoxyflavonoids (PMFs), the main compound in KP, also increased TG accumulation. This study therefore showed that KPE enhanced the thermogenesis effect of brown adipocytes as well as promoted the differentiation of brown adipocyte cells.