| 1. |
- Höglund, P, et al.
(författare)
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Antiarrhythmic effect of amperozide, a novel psychotropic compound with class III antiarrhythmic properties, on digoxin-induced arrhythmias in the guinea-pig
- 1986
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Ingår i: Journal of Pharmacy and Pharmacology. - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 38:11, s. 3-861
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Tidskriftsartikel (refereegranskat)abstract
- Amperozide is a novel psychotropic compound with specific effect in limbic brain areas. Preliminary findings have also indicated an antiarrhythmic effect in-vitro. Injections of saline, amperozide, melperone, thioridazine, bretylium or lignocaine, were given i.p. to anaesthetized guinea-pigs, which 10 min later were given digoxin s.c. to induce arrhythmia. In a series of control experiments none of these compounds caused arrhythmia in combination with the vehicle of digoxin. The time to arrhythmia was significantly prolonged after treatment with amperozide, melperone and bretylium compared with saline, but there were no differences between the treatments. The digoxin concentrations in plasma at death varied considerably within the groups and no statistical significance was found.
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| 2. |
- Alhalaweh, Amjad, et al.
(författare)
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Formation of cocrystals by spray drying
- 2010
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Ingår i: Journal of Pharmacy and Pharmacology (JPP). - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 62:10 - Special issue, s. 1332-1333
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Spray drying is a widely used technique for material processing and scale-up. The cocrystals formation by spray drying is studied. In contrast to solvent evaporation method, spray drying of stiochiometric solutions of incongruently saturating cocrystals had generated pure cocrystals. The formation phenomena in spray drying could be kinetically controlled or mediated by glassy state.
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| 3. |
- Björkman, Sven, et al.
(författare)
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Thermic and tremorogenic effects of thyroliberin (TRH) in reserpine-treated mice--the non-involvement of GABA-ergic mechanisms.
- 1981
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Ingår i: Journal of Pharmacy and Pharmacology (JPP). - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 33:9, s. 580-585
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Tidskriftsartikel (refereegranskat)abstract
- Administration of thyroliberin (TRH) to reserpinized mice causes tremor and counteracts the hypothermia in a dose-dependent fashion. The thyroliberin response is inhibited by gamma-hydroxybutyric acid (GHB) and baclofen, but not by other, more specific GABA-ergic agents, such as THIP, gamma-acetylenic GABA, and sodium valproate. Picrotoxin neither potentiates nor inhibits the thyroliberin actions. Nor are the thyroliberin effects dependent on cholinergic, monoaminergic or histaminergic mechanisms. The results repudiate a current hypothesis, that the peptide actions may be mediated by GABA-ergic pathways in the brain.
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| 4. |
- Chakraborty, Subhashis, et al.
(författare)
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Effective in-vivo utilization of lipid-based nanoparticles as drug carrier for carvedilol phosphate
- 2011
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Ingår i: Journal of Pharmacy and Pharmacology (JPP). - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 63:6, s. 774-779
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Lipid nanoparticles as carrier for oral drug administration improve gastrointestinal solubility of poorly soluble drugs and thus enhance bioavailability. However, basic drugs may undergo rapid dissolution from such solid dispersions in the stomach and precipitate in the intestine due to their higher solubility in acidic medium. Therefore, the objective of this work was to study the enhancement in bioavailability of carvedilol phosphate (basic drug) by providing an alkaline gastric environment to drug-loaded solid lipid nanoparticles. Methods An alkaline gastric environment in rats was created and maintained with oral administration of an antacid suspension 5 min before and 30 min post dosing. Key findings The formulation administered orally exhibited enhanced bioavailability (∼27%) when compared with drug suspension and sustained release behaviour when compared with formulation under ideal gastric conditions. The enhanced bioavailability is due to the presence of lipid nanoparticles as drug carrier while the sustained-release characteristic may be attributed to the presence of antacid, which resulted in elevation of gastric pH and reduced the drug's solubility. Conclusions It may be concluded that although lipid nanoparticles can be instrumental in improving bioavailability, additional sustained release may be achieved by targeting intestinal release of basic drugs from lipid vehicles, which is possible by incorporating them into suitable enteric-coated formulations.
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| 5. |
- Dew, Noel, 1980-, et al.
(författare)
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Novel Gel Formulations with Catanionic Aggregates Enable Prolonged Drug Release and Reduced Skin Permeation
- 2011
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Ingår i: Journal of Pharmacy and Pharmacology (JPP). - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 63:10, s. 1265-1273
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to investigate skin permeation rates of a drug substance when applied in novel gel formulations with catanionic aggregates. Methods: Reference gel without catanionic aggregates was compared with formulations with catanionic aggregates composed of tetracaine and either sodium dodecyl sulphate (SDS) or capric acid. Carbomer and SoftCAT were used to compare the effect of different gel types to elucidate if physically cross-linked, 'self-destructing' systems had benefits compared with classical, covalently cross-linked, gels. Key findings: The rheological investigation showed that the interactions between the SoftCAT polymer and tetracaine/SDS aggregates were stronger than when the tetracaine/capric acid aggregates were used. The skin permeation was measured ex vivo in horizontal Ussing chambers and the permeation of tetracaine was significantly lower when formulations with tetracaine/SDS aggregates were applied (P < 0.001), but not statistically different from the reference when capric acid was used. Conclusions: No morphological differences could be distinguished between the skin samples exposed to the different formulations or the reference. Skin permeation was compared with silicone sheet permeation and the results indicated that silicone sheets could be used as a model of skin when using these formulations.
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| 6. |
- Jung, Min-Sook, et al.
(författare)
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Bioavailability of indomethacin-saccharin cocrystals
- 2010
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Ingår i: Journal of Pharmacy and Pharmacology (JPP). - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 62:11, s. 1560-1568
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Tidskriftsartikel (refereegranskat)abstract
- Pharmaceutical cocrystals are new solid forms with physicochemical properties that appear promising for drug product development. However, the in-vivo bioavailability of cocrystals has rarely been addressed. The cocrystal of indomethacin (IND), a Biopharmaceutical Classification System class II drug, with saccharin (SAC) has been shown to have higher solubility than IND at all pH. In this study, we aimed to evaluate the in-vitro dissolution and in-vivo bioavailability of IND-SAC cocrystals in comparison with IND in a physical mixture and the marketed product Indomee (R).MethodsScale-up of the cocrystals was undertaken using cooling batch crystallisation without seeding. The chemical and physical purity of the up-scaled material was verified using high-performance liquid chromatography, differential scanning calorimetry and powder X-ray diffraction. The IND-SAC cocrystals and IND plus SAC were mixed with lactose and the formulations were placed into gelatin capsules. In-vitro dissolution studies were then performed using the rotating basket dissolution method. The intrinsic dissolution rate of IND and IND-SAC cocrystals was also determined. Finally, a bioavailability study for the formulations was conducted in beagle dogs. The plasma samples were analysed using high-performance liquid chromatography and the pharmacokinetic data were analysed using standard methodologies.Key findingsThe bulk cocrystals (i.e. scaled-up material) were chemically and physically pure. The in-vitro dissolution rate of the cocrystals was higher than that of IND and similar to that of Indomee (R) at pH 7.4 and pH 1.2. The in-vivo bioavailability of the IND-SAC cocrystals in dogs was significantly higher (ANOVA, P < 0.05) than that of IND but not significantly different from Indomee (R) (ANOVA, P > 0.05).ConclusionsThe study indicates that the improved aqueous solubility of the cocrystals leads to improved bioavailability of IND. Thus, the cocrystals are a viable alternative solid form that can improve the dissolution rate and bioavailability of poorly soluble drugs.
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| 7. |
- Karlsson, Britt M., et al.
(författare)
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The effect of the calcium antagonist nimodipine on the detoxification of soman in anaesthetized rabbits.
- 1997
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Ingår i: Journal of Pharmacy and Pharmacology (JPP). - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 49:3, s. 296-300
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Tidskriftsartikel (refereegranskat)abstract
- The effect of nimodipine, a vasoactive calcium antagonist, on the disappearance of soman from blood was studied in anaesthetized rabbits intoxicated with soman (10.8 micrograms kg-1 i.v.). Blood samples from the left heart ventricle and femoral artery were used to investigate soman detoxification. The concentrations of the soman isomers C+P- and C-P- in blood samples were determined by gas chromatography coupled with high-resolution mass spectrometry. During the sampling, 15-300 s after soman injection, the soman concentration in control animals decreased from 50 to 0.029 ng mL-1; in animals pre-treated with nimodipine (10 mg kg-1) it decreased from 15 to 0.033 ng mL-1. In animals pre-treated with nimodipine the soman concentration was significantly reduced during the first minute of sampling. No differences were detected between soman concentrations in samples from the heart and femoral artery. Acetylcholinesterase inhibition was also used as an indicator of soman activity; there was no difference between the activity of this enzyme in different peripheral organs of control and nimodipine-treated animals. Nimodipine reduces the initial concentration of soman in the blood, which might be of significance in the treatment of soman intoxication.
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| 8. |
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| 9. |
- Mohammad, Mohammad Amin, et al.
(författare)
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Utility of Hansen solubility parameters in the cocrystal screening
- 2010
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Ingår i: Journal of Pharmacy and Pharmacology (JPP). - 0022-3573 .- 2042-7158. ; 62:10 - Spec issue, s. 1360-1362
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The objective of this study was to test if the miscibility between drug and coformer, as predicted by solubility parameters, can be used as a tool in the cocrystal research. Hansen Solubility Parameters (HSPs) of a model drug, indomethacin and thirty coformers were calculated according to the group contribution method. The distances in HSPs between indomethacin and each cocrystal former were then calculated using three validated miscibility tools. Twenty coformers were predicted and confirmed to be miscible with the drug. Interestingly, all cocrystals forming systems were miscible. Two new cocrystal systems were discovered through this approach. Therefore, the utility of the solubility parameters approach can enhance the effi ciency of cocrystal screening.
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| 10. |
- Berggren, S, et al.
(författare)
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Regional transport and metabolism of roivacaine and its CYP3A4 metabolite PPX in human intestine
- 2003
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Ingår i: Journal of Pharmacy and Pharmacology. - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 55:7, s. 963-972
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Tidskriftsartikel (refereegranskat)abstract
- The major aim of this study was to investigate the CYP3A4 metabolism and polarized transport of ropivacaine and its metabolite 2',6'-pipecoloxylidide (PPX) in tissue specimens from the human small and large intestine. Ropivacaine has been shown to be effective in the treatment of ulcerative colitis in human colon. This study was conducted using a modified Ussing-chamber technique with specimens from jejunum, ileum and colon collected from 11 patients. The local kinetics of ropivacaine and PPX were assessed from their concentration-time profiles in mucosal and serosal compartments. The permeability (P-app) in the absorptive direction for both ropivacaine and PPX increased regionally in the order jejunum
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