| 1. |
- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- Kolettis, Theofilos M, et al.
(författare)
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Dose-dependent effects of sildenafil on post-ischaemic left ventricular function in the rat isolated heart.
- 2010
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Ingår i: The Journal of pharmacy and pharmacology. - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 62:3, s. 346-51
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Sildenafil may be beneficial during myocardial ischaemia/reperfusion, but this effect may be dose-dependent, accounting for previous conflicting results. We have explored the effects of two acute and one chronic administration regimen on left ventricular function. METHODS: The study was conducted on 36 Wistar rats (290 +/- 7 g). Sildenafil was administered 30 min before ischaemia at a low (0.7 mg/kg, n= 8) or high (1.4 mg/kg, n= 8)dosage. The chronic treatment arm (n= 8) consisted of two daily injections of sildenafil (0.7 mg/kg) for three weeks. The control group was formed by 12 rats. Ischaemic contracture, post-ischaemic recovery and hypercontracture were measured in isolated, Langendorff-perfused preparations. KEY FINDINGS: Ischaemic contracture tended to be lower after high-dose sildenafil, while remaining unchanged after low-dose or chronic sildenafil administration. Compared with controls (62.9 +/- 2.0% of baseline developed pressure), post-ischaemic recovery was higher (P= 0.0069) after low dose (75.1 +/- 2.4%), unchanged (P= 0.13) after high dose (69.1 +/- 2.1%), but lower (P < 0.001) after chronic (42.9 +/- 4.5%) sildenafil administration. Compared with controls (71.8 +/- 3.9 mmHg), hypercontracture was higher (P= 0.0052) after chronic sildenafil administration (89.5 +/- 4.1 mmHg), but similar after acute low dose (65.7 +/- 3.3 mmHg, P= 0.33) or high dose (67.1 +/- 4.7 mmHg, P= 0.43). CONCLUSIONS: The effects of sildenafil after ischaemia/reperfusion were strongly dose-dependent. Beneficial actions on left ventricular function were evident after acute pretreatment with a low dosage, but were lost after doubling the dose. Chronic sildenafil administration deteriorated left ventricular function during ischaemia and reperfusion.
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| 6. |
- Li, Jie, et al.
(författare)
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Regional variations of vasomotion to G-protein coupled receptor agonists following heat stress in rats
- 2010
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Ingår i: Journal of Pharmacy and Pharmacology. - 0022-3573. ; 62:3, s. 315-322
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Tidskriftsartikel (refereegranskat)abstract
- Objectives This study was designed to compare vascular contractile and relaxing responses to G-protein coupled receptor agonists among the different regions of arteries following heat stress in rats. Methods Heat exposure was performed by increasing the internal temperature of the rats to 42 degrees C for 15 min. After heat stress for 48 h, a rnyograph system was used to monitor the contractile responses in rat renal, femoral and mesenteric arteries to agonists of endothelin type B (ETB) receptor, endothelin type A (ETA) receptor, serotonin receptor and alpha-adrenoceptor, respectively. In addition, calcitonin gene-related peptide (CGRP)-induced vasodilation was studied. Key findings The results showed that heat stress induced decreased contractions mediated by alpha-adrenoceptors and serotonin receptors (at lower concentration), while it increased contraction mediated by endothelin ETB receptors and enhanced relaxation mediated by CGRP receptors in the renal artery. Heat stress increased contractions mediated by endothelin ETB receptors, endothelin ETA receptors and alpha-adrenoceptors in the femoral artery. In the mesenteric artery, heat stress increased contractions mediated by endothelin ETB and serotonin receptors and relaxation mediated by CGRP receptors. Conclusions The vasomotor responses to the G-protein coupled receptor agonists with altered vascular contractions and relaxations were different in rat renal, femoral and mesenteric arteries after heat stress. This might have contributed to the redistribution of blood flow and aids understanding of the preconditioning phenomenon.
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| 7. |
- Magnusson, B.M., et al.
(författare)
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Intra- and inter-individual variability in the development of erythema after application of methyl nicotinate evaluated by polarization spectroscopy imaging
- 2010
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Ingår i: JOURNAL OF PHARMACY AND PHARMACOLOGY, vol 62, issue 6, pp 801-801, ISSN: 002-3573. - : Pharmaceutical Press. ; , s. 801-801
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Konferensbidrag (refereegranskat)abstract
- The concept that the time to onset of erythema after the application of the rubefacient and urticant substance methyl nicotinate (MN) indicates skin barrier competence was introduced 30 years ago. MN produces a dose-dependent erythema on topical application to intact skin, the nature of which is known to be fast moving (in the order of minutes) and variable. Using tissue viability imaging (TiVi) the time course and degree of the reaction can be conveniently followed and analysed. Inter-individual variability can be quite marked but intra-individual variability is less pronounced. At the upper end of provocation (higher doses, more sensitive individuals) urtication can occur, which decreases blood flow by increasing pressure on and thus emptying capillaries. The TiVi system can quantitate urtication and inherent (blanched) skin colour. The utility of MN application in the study of individual barrier function and microvascular reactivity is increased by the use of the TiVi system for collection and analysis of data.
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| 8. |
- 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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| 9. |
- Morales, Javier O., et al.
(författare)
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Protein-coated nanoparticles embedded in films as delivery platforms
- 2013
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Ingår i: Journal of Pharmacy and Pharmacology (JPP). - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 65:6, s. 827-838
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This work aimed to evaluate the performance of nanoparticle-loaded films based on matrices of polymethacrylates and hydroxypropylmethylcellulose (HPMC) intended for delivery of macromolecules.METHODS: Lysozyme (Lys)-loaded nanoparticles were manufactured by antisolvent co-precipitation. After size, loading efficiency and stability characterization, the selected batch of particles was further formulated into films. Films were characterized for mechanical properties, mucoadhesion, Lys release and activity after manufacture.KEY FINDINGS: We found that protein-coated nanoparticles could be obtained in USP phosphate buffer pH 6.8. Particles obtained at pH 6.8 had a z-average of 347.2 nm, a zeta-potential of 21.9 mV and 99.2% remaining activity after manufacture. This formulation was further studied for its application in films for buccal delivery. Films loaded with nanoparticles that contained Eudragit RLPO (ERL) exhibited excellent mechanical and mucoadhesive properties. Due to its higher water-swelling and solubility compared with ERL, the use of HPMC allowed us to tailor the release of Lys from films. The formulation composed of equal amounts of ERL and HPMC revealed a sustained release over 4 h, with Lys remaining fully active at the end of the study.CONCLUSIONS: Mucoadhesive films containing protein-coated nanoparticles are promising carriers for the buccal delivery of proteins and peptides in a stable form.
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| 10. |
- Polentarutti, Britta, et al.
(författare)
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Modification of gastric pH in the fasted dog
- 2010
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Ingår i: Journal of Pharmacy and Pharmacology (JPP). - 0022-3573 .- 2042-7158. ; 62:4, s. 462-469
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim was to compare the ability of pretreatments to consistently adjust gastric conditions to low or high pH in the fasted state in dogs. METHODS: Four male Labrador/Labrador-cross dogs weighing 25-35 kg were surgically equipped with a ventricle fistula cannula in the stomach and a jejunal nipple valve stoma. Dogs were fasted overnight before the experiments, with free access to water. The pH in the dogs' stomach was modified either orally with buffers (0.1 mol/l HCl-KCl, 0.05 mol/l glycine-HCl, 0.1 mol/l citrate or 0.1 mol/l BIS-TRIS) or intravenously with pharmacological agents (pentagastrin 4-6 microg/kg, ranitidine 50 mg or omeprazole 1 mg/kg). Intragastric pH was recorded continuously for 2 h with an electrode connected to an ambulatory pH meter. Chyme was collected simultaneously from the jejunal stoma as an approximate measure of gastric emptying. KEY FINDINGS: 0.1 mol/l HCl-KCl buffer p.o. and 1 mg/kg omeprazole i.v. attained low and high gastric pH more reproducibly (11/11 and 6/7 experiments met target values of pH < 3 and > 4, respectively) and for a longer duration (average time exceeding target value 90 and 103 min, respectively) than the other buffers and pharmacological pretreatments. The starting pH did not alter the modifiers' capacity to increase or decrease the pH. However, the lag time before chyme appeared at the jejunal stoma appeared to be longer when the pH was low and shorter when the pH was high. CONCLUSIONS: To achieve a consistently low gastric pH in fasting dogs, 0.1 mol/l HCl-KCl buffer should be administered orally, 15 min before the dosage form. To elevate the gastric pH reproducibly, omeprazole 1 mg/kg should be administered intravenously at least 90 min before oral administration of the dosage form.
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