| 1. |
- Ahnfelt, Emelie, et al.
(författare)
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Lipiodol-based emulsions used for transarterial chemoembolization and drug delivery : Effects of composition on stability and product quality
- 2019
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Ingår i: Journal of Drug Delivery Science and Technology. - : ELSEVIER. - 1773-2247. ; 53
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Tidskriftsartikel (refereegranskat)abstract
- Transarterial chemoembolization with emulsion-based formulations using doxorubicin hydrochloride (DOX) and Lipiodol (R) is the golden standard for the loco-regional treatment of unresectable hepatocellular carcinoma (HCC). However, from a pharmaceutical quality perspective these emulsions are poorly characterized. In this study, clinically relevant Lipiodol (R)-based emulsions were characterized in terms of emulsion stability, continuous phase classification and droplet-size distribution. Also, the solubility of DOX in the different emulsion components and the distribution of DOX to the lipid phase were investigated. These are key features to investigate due to the claimed tumor-seeking properties of Lipiodol (R). The in vitro release of DOX was studied in a miniaturized dialysis method and an empirical release model was applied to adjust for the passage of DOX across the dialysis membrane. The most stable emulsion ( > 72 h) was classified as water-in-oil (w/o), had the highest distribution of DOX to the lipid phase (20%) and an aqueous-to-lipid phase ratio of 1:4. The composition of the aqueous phase was a mixture (v/v) of iohexol (85%) and water (15%). Emulsions containing iohexol and a high aqueousto-lipid phase ratio (1:2-1:4) displayed prolonged in vitro release profiles of DOX. This study further emphasizes the medical need to standardize these emulsion-based drug delivery systems.
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| 2. |
- AlHayali, Amani, et al.
(författare)
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Silodosin oral films : Development, physico-mechanical properties and in vitro dissolution studies in simulated saliva
- 2019
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Ingår i: Journal of Drug Delivery Science and Technology. - : Elsevier. - 1773-2247. ; 53
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Tidskriftsartikel (refereegranskat)abstract
- Sublingual film dosage forms for drugs used for fast symptomatic treatment have promise because they allow a rapid onset of action. The aim of this study was to prepare films of silodosin intended for sublingual administration for the symptomatic treatment of benign prostatic hyperplasia in men. Hydroxypropyl methylcellulose (HPMC) or hydroxypropyl methylcellulose acetate succinate (HPMC-AS) were used as film-forming polymers. The effects of the polymers and the surfactant tocopherol polyethylene glycol succinate (TPGS) on the physico-mechanical properties and dissolution behavior of the films in simulated saliva were investigated. The eight silodosin oral films developed (F1–F8) contained 8 mg silodosin per 6 cm2 film and HPMC or HPMC-AS in drug:polymer ratios of 1:5 or 1:3, while four also contained TPGS (0.5% w/w). The films were characterized using DSC, TGA, SEM, and PXRD and the mechanical properties were investigated by measuring tensile strength, elongation at break and Young's modulus. The mechanical properties of the films were dependent on the ratio of polymer used. The in vitro dissolution and drug release studies indicated that HPMC-AS films disintegrated more quickly than HPMC films. Silodosin was shown to be dispersed within the polymers. Despite silodosin being submicronized in the HPMC films, the dissolution and drug release rate (time for 80% release) from HPMC films was significantly faster than from HPMC-AS films. TPGS increased the drug release rate to a greater extent with HPMC than with HPMC-AS. The degree of saturation of formulation F4 was >1, which shows potential for improving oral absorption of silodosin.
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| 3. |
- Ali, Abdullah, 1985-, et al.
(författare)
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Will a water gradient in oral mucosa affect transbuccal drug absorption?
- 2018
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Ingår i: Journal of Drug Delivery Science and Technology. - : Elsevier. - 1773-2247. ; 48, s. 338-345
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Tidskriftsartikel (refereegranskat)abstract
- Formulations for buccal drug delivery often comprise polymers to facilitate mucoadhesion based on water sorption. The main objective of the current study was therefore to evaluate the effect of dehydration on drug uptake through oral mucosa. We have used diffusion cells with excised porcine mucosa to study uptake of three alternative drugs (i.e., Metronidazole, Benzydamine and Xylometazoline) together with polyethylene glycol (PEG) as the model polymer for adjusting water activity in the test solutions. Taking drug activity into account, we can conclude that addition of PEG results in a drug flux through mucosa that is about two times lower for Metronidazole and more than 40 times lower for Xylometazoline compared to that from a pure PBS-solution. However, for Benzydamine the uptake through mucosa was more or less the same, which could possibly be due to the high PEG-concentration (65 wt%) affecting the dissociation constant and thus the permeability. These results indicate that an increased water gradient may have the same limiting effect on permeability through oral mucosa as previously seen for skin. Thus, water gradient effects should be a factor to consider when developing buccal adhesive formulations.
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| 4. |
- Bakardzhiev, Pavel, et al.
(författare)
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Novel polyglycidol-lipid conjugates create a stabilizing hydrogen-bonded layer around cholesterol-containing dipalmitoyl phosphatidylcholine liposomes
- 2015
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Ingår i: Journal of Drug Delivery Science and Technology. - : Elsevier. - 1773-2247. ; 29, s. 90-98
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Tidskriftsartikel (refereegranskat)abstract
- Hybrid liposomes resulting from co-assembly of dipalmitoylphosphatidylcholine and polyglycidol-derivatized lipids were prepared. The latter were composed of a lipid-mimetic residue to which a linear polyglycidol chain (degree of polymerization, DP, in the 23–110 range) was conjugated. Formulations with varying copolymer type and content were prepared by film hydration technique followed by extrusion. The hybrid structures were studied by means of dynamic and electrophoretic light scattering, cryogenic transmission electron microscopy, and fluorescence spectroscopy. Cytotoxicity towards OPM-2 (multiple myeloma) and EJ (human urinary bladder carcinoma) cell lines was assessed as well. Predominantly unilamellar liposomes with mean hydrodynamic diameters in the 113–134 nm range and neutral to slightly negative surface potential were prepared. The integrity of liposomes containing copolymers with DP of the polyglycidol chain 23 and 30 was preserved at copolymer contents up to 10 mol%. Bilayer disks were observed at somewhat lower contents of the copolymers of the highest DP of the polyglycidol chain. The hybrid structures were less leaky than the plain liposomes, which was attributed to formation of a strongly hydrogen-bonded polyglycidol layer around the bilayer membrane. They exhibited low toxicological potential, favorable physicochemical characteristics, and ability to act as containers for sustained release.
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| 5. |
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| 6. |
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| 7. |
- Gulsun, T., et al.
(författare)
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Preparation and characterization of furosemide nanosuspensions
- 2018
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Ingår i: Journal of Drug Delivery Science and Technology. - : Elsevier BV. - 1773-2247. ; 45, s. 93-100
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Tidskriftsartikel (refereegranskat)abstract
- Furosemide, a widely used loop diuretic, has a low aqueous solubility, and low permeability. Nanosuspensions have been widely used to increase the solubility of poorly soluble drugs. The aim of this study was to develop and characterize furosemide containing nanosuspensions. Furosemide nanosuspensions with Tween 80, were prepared using high pressure homogenization method using ultrasonic probe or ultra turrax, ball milling method, and combination of these methods. The physicochemical properties of furosemide, physical mixture and nanosuspensions were evaluated by FT-IR, DSC and X-ray analyses. Particle size, polydispersity index, zeta potential, solubility and permeability of nanosuspensions were also determined. FT-IR analysis revealed that characteristic peaks of furosemide were seen in all formulations. X-ray analysis indicated that crystalline structure of furosemide was preserved in nanosuspensions. The particle size of furosemide decreased significantly (p < 0.05) by using nanosuspension technology. Furosemide solubility was pH-dependent, and impact of nanosuspension on the solubility was more pronounced at lower pH values (e.g. pH 1.2). Furosemide permeability seemed to be influenced by nanosuspension preparation method. In conclusion, nanosuspension technology seems to be a promising approach for enhancement of solubility and permeability properties of poorly water soluble compounds, and it has an excellent potential to improve the bioavailability of such compounds. © 2018 Elsevier B.V.
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| 8. |
- Hagen, Eirik, et al.
(författare)
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Use of interactive mixtures to obtain mini-tablets with high dose homogeneity for paediatric drug delivery
- 2016
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Ingår i: Journal of Drug Delivery Science and Technology. - : Elsevier BV. - 1773-2247. ; 34, s. 51-59
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Tidskriftsartikel (refereegranskat)abstract
- Mini-tablets are suitable for children since they are easy to swallow and offer dose flexibility by adjustment of the number of units. The main objective was to investigate the use of interactive mixtures as a means to obtain high dose homogeneity in mini-tablets. The effect of carrier particle properties, mixing time, mixing equipment and sample size on homogeneity was evaluated. Micronized sodium salicylate (1% w/w) was mixed with different size fractions of spray-dried and granulated mannitol. The degree of homogeneity was expressed as the relative standard deviation (RSD). Mini-tablets were prepared from the interactive mixtures and characterized with respect to uniformity of mass and content, dose homogeneity, tablet strength, wetting time and disintegration time. Generally, RSD decreased with increasing mixing times, and levelled out around 3-4%. The lowest RSD was achieved with carrier particles of intermediate sizes; 125-180 mu m, 180-250 mu m and 250-355 mu m. The tumbling mixer was considered to be more suitable than the planetary mixer and longer mixing times were required to reach high degree of homogeneity in the smaller sample size. Mini-tablets showed high dose homogeneity as well as appropriate tensile strength and disintegration time to be suitable as orally disintegrating mini-tablets for children.
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| 9. |
- Vijayakumar, Mahalingam Rajamanickam, et al.
(författare)
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Trans resveratrol loaded DSPE PEG 2000 coated liposomes: An evidence for prolonged systemic circulation and passive brain targeting
- 2016
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Ingår i: Journal of Drug Delivery Science and Technology. - : Elsevier BV. - 1773-2247. ; 33, s. 125-135
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Tidskriftsartikel (refereegranskat)abstract
- Trans resveratrol (RSV) is a natural molecule proved for cardioprotective effects, vasodilation, anti-inflammatory, cancer preventive and therapeutic activities devoid of any potential side effects. Recently, anti cancer potential against glioma cells were also reported with proven molecular mechanisms. However, the therapeutic application of RSV in clinical disease management is restricted because of its rapid elimination from systemic circulation and thereby low biological half life in mammals. Therefore, the main objective of this study was to improve the systemic circulation and biological half life of RSV using DSPE PEG 2000 decorated (PEGylated) liposomes. Moreover, brain distribution of RSV loaded PEGylated liposomes (RSV-PEG-Lipo) and non-PEGylated liposomes (RSV-Lipo) was also evaluated for proving their passive brain targeting ability. In vitro drug release of both liposomes was found to be sustained up to 48 h. RSV-PEG-Lipo showed higher area under the curve, plasma half life and mean residence time and lower volume of distribution and clearance than that of pristine RSV solution and RSV-Lipo. Pharmaokinetics results clearly indicated that the RSV-PEG-Lipo will be promising tool for enhancing plasma half life and prolong the systemic circulation of RSV. Brain distribution studies revealed that the liposomal formulations can be applied as an effective tool for passive brain targeting useful in the treatment of glioma.
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