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Biomedical subjects

V Tantishaiyakul

Publications and source records attributed to V Tantishaiyakul.

8 recordsLinked to original sources
PubMed2001

Studies on aging piroxicam-polyvinylpyrrolidone solid dispersions.

The stabilities of X-ray amorphous solid dispersions of piroxicam and polyvinylpyrrolidone (PVP) K-17 and PVP K-30 (1:5 and 1:4), respectively, were investigated after storage for 12 months. X-ray diffraction showed that in the aged solid dispersions piroxicam remained in the amorphous state. Fourier transform infrared (FTIR) spectroscopy indicated that the interactions between drug and PVP in aged solid dispersions are similar to those in freshly prepared samples. The dissolution rates of the X-ray amorphous solid dispersions during storage for 12 months at 45 degrees C and ambient temperature were examined. Very minor decreases in dissolution rates of aged solid dispersions were found which might be due to the coarsening of the particles. Dissolutions of these amorphous solid dispersions after aging for 12 months still showed an about 40-fold increase in dissolution in 5 min compared to pure drug.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Prediction of Caco-2 cell permeability using partial least squares multivariate analysis.

The permeability across Caco-2 cell monolayers of structurally diverse compounds were predicted using computed molecular descriptors and multivariate. Partial Least Squares (PLS). The molecular descriptors including log polarization, log solvent accessible surface area, hydration energy, heat of formation, and dipole moment were calculated with Hyperchem and ChemPlus QSAR programs for Windows. Other physiochemical properties such as hydrogen acceptor for oxygen atoms, hydrogen acceptor for nitrogen atoms, hydrogen bond donors, hydrogen bond forming ability, molecular weight, and log distribution coefficient were also used as descriptors. Cross validation with internal test set and prediction with external test set indicated the usefulness of the derived model for Caco-2 cell permeability. Hydrogen bonding is one of the important factors associated with permeability. While increased logD and hydration energy facilitate permeability, an increased dipole moment of molecules has a negative effect on permeability.

Algorithms↗
PubMed1999

Properties of solid dispersions of piroxicam in polyvinylpyrrolidone.

Solid dispersions of piroxicam were prepared with polyvinylpyrrolidone (PVP) K-17 PF and PVP K-90 by solvent method. The physical state and drug:PVP interaction of solid dispersions and physical mixtures were characterized by X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). FTIR analysis demonstrated the presence of intermolecular hydrogen bonding between piroxicam and PVP in solid dispersions. These interactions reflected the changes in crystalline structures of piroxicam. The amorphousness within the PVP moeity might be predicted in piroxicam dispersions by the disappearance of N-H or O-H peak of piroxicam. Dissolution studies indicated a significant increase in dissolution of piroxicam when dispersed in PVP. The better results were obtained with the lower molecular weight PVP K-17 than with higher molecular weight PVP K-90. The non-amorphous solid dispersions in PVP K-17 showed almost equally fast dissolution rates to amorphous dispersions in PVP K-90. The mechanism of dissolution of solid dispersion in PVP K-90 is predominantly diffusion-controlled due to the very high viscosity of PVP K-90. Dissolution was maximum with the amorphous solid dispersions containing drug:PVP K-17 1:5 and 1:6 which showed a 40-fold increase in dissolution in 5 min as compared with pure drug.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Simultaneous determination of dextromethorphan HBr and bromhexine HCl in tablets by first-derivative spectrophotometry.

A rapid, simple and direct assay procedure based on first-derivative spectrophotometry, using a zero-crossing and peak-to-base measurement at 234 and 324 nm, respectively, has been developed for the specific determination of dextromethorphan HBr and bromhexine HCl in tablets. Calibration graphs were linear with the correlation coefficients of 0.9999 for both analytes. The limit of detections were 0.033 and 0.103 microgram ml-1 for dextromethorphan HBr and bromhexine HCl, respectively. A HPLC method has been developed as the reference method. The results obtained by the first-derivative spectrophotometry were in good agreement with those found by the HPLC method.

Antitussive Agents↗
PubMed1993

Halogen-substituted trimetoquinol analogs as thromboxane A2 receptor antagonists in platelets and aorta.

Trimetoquinol (TMQ) is a non-prostanoid compound that blocks prostaglandin H2/thromboxane A2 (TXA2) receptor-mediated responses initiated by a prostaglandin (PG) H2 analog, U46619, in human platelets and rat aorta. Ring fluorine-substituted TMQ analogs selectively antagonized PG-dependent human platelet activation induced by U46619, arachidonic acid, collagen, ADP or epinephrine; and were about 300-fold less potent as inhibitors of PG-independent responses mediated by thrombin or bacterial phospholipase C. For each inducer of the PG-dependent pathway, the rank order of inhibitory potency was identical (TMQ > 8-fluoro-TMQ > 5-fluoro- TMQ). Iodine substitution yielded a similar rank order of antagonism against U46619-induced platelet activation (TMQ > 8-iodo-TMQ > 5-iodo-TMQ), and all TMQ analogs inhibited platelet aggregation in whole blood as well as in platelet-rich plasma. Inhibition of specific [3H]SQ 29,548 binding by TMQ analogs was highly correlated with inhibition of functional responses to U46619. Radioligand binding experiments using TMQ analogs with rat platelets showed no interspecies difference in comparison with human platelets. The rank order of inhibitory potencies for the fluorinated (but not iodinated) TMQ analogs changed in rat thoracic aorta with 8-fluoro-TMQ > TMQ > or = 5-fluoro-TMQ as antagonists of U46619-induced vascular contraction. These findings demonstrate that the primary mechanism of antiplatelet action of TMQ analogs is related to a blockade of TXA2 receptor sites, and ring-halogenated TMQ analogs distinguish between TXA2-mediated functional responses in vascular smooth muscle and platelets.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Synthesis of halogenated trimetoquinol derivatives and evaluation of their beta-agonist and thromboxane A2 (TXA2) antagonist activities.

The 5,8-difluoro (4), 5-iodo (5), 8-iodo (6), and 5-trifluoromethyl (7) derivatives of trimetoquinol (TMQ, 1) have been synthesized and evaluated for their ability to stimulate beta 1 (guinea pig atria) and beta 2 (guinea pig trachea) adrenoceptors as well as for their inhibitory activity against U46619 [a thromboxane A2 (TXA2) mimetic]-mediated contraction of rat thoracic aorta and human platelet aggregation. Both 5 and 6 were considerably less active than TMQ on both beta-adrenergic systems and gave a rank order of stimulatory potency of 1 much greater than 6 greater than or equal to 5. Similarly, iodine substitution at either position also caused a reduction in TXA2 antagonist activity with a rank order potency of 1 greater than 6 much greater than 5. Compared to 1, however, 5-iodo-TMQ (5) showed a marked selectivity for blockade of U46619 responses in rat aorta over human platelets. On beta-systems, 4 had reduced potency compared to TMQ and was similarly nonselective. Introduction of a trifluoromethyl group at the 5-position of TMQ completely abolished both beta 1- and beta 2-adrenergic agonist activities while imparting weak antagonist activity on beta 1 receptors. On TXA2 systems, both 4 and 7 possessed significantly decreased inhibitory activity compared to TMQ. The synthetic approaches to the synthesis of 8-(trifluoromethyl)-TMQ (8) are also described. The enantiomers of the 8-fluoro derivative (3) of TMQ were separated on a preparative Chiralcel OD column and evaluated on beta-adrenergic systems and TXA2 systems. On beta-adrenergic systems, (S)-(+)-8-fluoro-TMQ was at least 10-fold more potent than (R)-(-)-8-fluoro-TMQ. Conversely, (R)-(-)-8-fluoro-TMQ was approximately 14-fold more potent as an antagonist of TXA2-mediated aggregation in human platelets than (S)-(+)-8-fluoro-TMQ. In contrast to platelets, (S)-(+)-8-fluoro-TMQ was an agonist in rat aorta whereas (R)-(-)-8-fluoro-TMQ was an antagonist.

Adrenergic beta-Agonists↗
PubMed1991

Structure-activity studies of new imidazolines on adrenoceptors of rat aorta and human platelets.

Potencies of new aromatic substituted fluoro or iodo analogues of catecholimidazolines on functional responses in rat aorta (alpha 1) and platelets (alpha 2) were quantified. (1) When compared either on the basis of EC50 or the dissociation constant (KA), 5-fluorocatecholimidazoline was as potent as the reference alpha 1-adrenoceptor agonist, phenylephrine in the vascular tissue. The maximum contraction of aorta produced by the fluoro analogue was, however, 17% higher than that of phenylephrine. The time required for 1/2 relaxation of the tissue after 5-fluoro hydroxy imidazoline was at least twice as long as that of the phenylephrine. The catechol moiety as well as fluorine substitution at the critical 5-position of the aromatic ring is essential for higher alpha 1 adrenoceptor-mediated potency. (2) As compared to the fluoro analogues, the adrenoceptor-mediated potencies of iodo-analogues were relatively weak on vascular tissue. Naphazoline and its analogues were partial agonists on vascular tissue with dissociation constants which ranged from 110 to 2600 nmol/l. (3) Imidazole analogues were generally less potent agonist than the imidazolines by one order of magnitude. (4) The vacular effects of all agonists were competitively blocked by prazosin with KB values which ranged from 0.04 to 0.48 nmol/l. Since the variation in KB values were within normal limits, the action of new imidazolines on rat aorta appears to be mediated mainly by the activation of the alpha 1-adrenoceptor. Prazosin 10 nmol/l abolished the vascular response of some partial agonists. This indicates a slightly different mode of interaction of agonists with the transduction process. (5) Carbon 4-substituted imidazolines produced little or no alpha 1 adrenoceptor-mediated intrinsic activity, but competitive receptor blocking potency was comparable to that of phentolamine. (6) Medetomidine was a partial agonist on the rat aorta with a KA of 260 nmol/l. When investigated as a blocker, the KB of medetomidine against phenylephrine was approximately 5600 nmol/l. The variation in the latter value was high. (7) In acetylsalicylic acid-treated human platelets, the alpha 2-adrenoceptor-mediated aggregatory effect of all fluoro analogues was weak. Iodo or naphazoline analogues did not initiate platelet aggregation but blocked the aggregation induced by epinephrine. The affinity of naphazoline for the alpha 2-adrenoceptor was 1100 nmol/l. The IC50 of medetomidine for platelet anti-aggregatory effect was 3300 nmol/l, which compares favorably with other imidazoline type of blockers of platelet aggregation. (8) Sympathomimetic vasoconstrictor actions and platelet aggregation effects of these compounds can be dissociated.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗