| 1. |
- Abrahmsén-Alami, Susanna, et al.
(author)
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New release cell for NMR microimaging of tablets Swelling and erosion of poly(ethylene oxide)
- 2007
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In: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 342:1-2, s. 105-114
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Journal article (peer-reviewed)abstract
- A small release cell, in the form of a rotating disc, has been constructed to fit into the MRI equipment. The present work show that both qualitative and quantitative information of the swelling and erosion behavior of hydrophilic extended release (ER) matrix tablets may be obtained using this release cell and non-invasive magnetic resonance imaging (MRI) studies at different time-points during matrix dissolution. The tablet size, core size and the gel layer thickness of ER matrix formulations based on poly(ethylene oxide) have been determined. The dimensional changes as a function of time were found to correspond well to observations made with texture analysis (TA) methodology. Most importantly, the results of the present study show that both the erosion (displacement of the gel-dissolution media interface) and the swelling (decrease of dry tablet core size) proceed with a faster rate in radial than in axial direction using the rotating disk set-up. This behavior was attributed to the higher shear forces experienced in the radial direction. The results also indicate that front synchronization (constant gel layer thickness) is associated with the formation of an almost constant polymer concentration profile through the gel layer at different time-points.
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| 2. |
- Tajarobi, Farhad, 1971, et al.
(author)
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Simultaneous probing of swelling, erosion and dissolution by NMR-microimaging – Effect of solubility of additives on HPMC matrix tablets
- 2009
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In: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 37:2, s. 89-97
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Journal article (peer-reviewed)abstract
- Extensive studies of extended release tablets based on hydrophilic polymers have illuminated severalaspects linked to their functionality. However, in some respects key factors affecting the mechanismsof release are yet unexplored. In the present study, a novel NMR-microimaging method has been usedto study the influence of the solubility of additives in extended release hydroxypropyl methylcellulose(HPMC) matrix tablets. During the course of the tablet dissolution the movement of the swelling anderosion fronts were studied simultaneously to the release of both polymer and additives. Moreover,the focused beam reflectance measurement (FBRM) technology was for the first time assessed for bothrelease and dissolution rate studies of poorly soluble particles. The studied formulations comprised solelyHPMC, 40% HPMC and 60% mannitol (Cs = 240 mg/ml) and 40% HPMC and 60% dicalcium phosphate (DCP)(Cs = 0.05 mg/ml). The dissolution rate of the tablets was highest for the HPMC/mannitol formulation,followed by HPMC/DCP and plain HPMC tablet. A contrasting order was found regarding the degree andkinetics of swelling. The results were interpreted in light of how the mass transport in the gel layer isinfluenced by the solubility of additives. A mechanistic model, considering osmotic pressure gradient andthe effective diffusion of the dissolution medium in the gel is proposed.
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| 3. |
- Tajarobi, Farhad, 1971, et al.
(author)
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The Impact of Dose and Solubility of Additives on the Release from HPMC Matrix Tablets-Identifying Critical Conditions
- 2009
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In: Pharmaceutical Research. - : Springer Science and Business Media LLC. - 1573-904X .- 0724-8741. ; 26:6, s. 1496-1503
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Journal article (peer-reviewed)abstract
- Purpose. The dissolution of HPMC matrix tablets containing different amounts of highly soluble(mannitol) or poorly soluble (dicalcium phosphate, DCP) was studied to deduce the parameters criticalto release robustness.Methods. The release of HPMC and additives was studied using a modified USP II method at two paddlestirring rates, 50 and 125 rpm, at HPMC content varying from 15% to 100%.Results. At HPMC contents between 30% and 35% a critical point was identified and found crucial to therelease from the HPMC/mannitol tablets. Below this point the matrix rapidly disintegrated in a non robustmanner. At higher HPMC contents the mannitol release became increasingly diffusion controlled withmaintained matrix integrity. The release robustness was lower for HPMC/DCP than HPMC/mannitoltablets at high HPMC contents, however, lacking critical points. The critical point was interpreted as thepercolation threshold for HPMC and differences explained in terms of water transport into the matrix.Conclusion. The release robustness was lower for formulations with additives of low solubility having anerosion controlled release than for additives with higher solubility and a diffusion controlled release.However, for additives creating a steep osmotic pressure gradient, an HPMC content above thepercolation threshold becomes vital for maintaining the release robustness.
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| 4. |
- Trotzig, Charlotte, et al.
(author)
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Structure and mobility in water plasticized poly(ethylene oxide)
- 2007
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In: Polymer. - : Elsevier BV. - 0032-3861. ; 48:11, s. 3294-3305
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Journal article (peer-reviewed)abstract
- The change in structure and mobility of poly(ethylene oxide) (PEO) containing 2 wt% of fumed silica and the water self-diffusion coefficient in concentrated PEO-water systems have been investigated at room temperature in the water weight fraction, w(w) range 0-0.50 w/w. Pulsed field gradient nuclear magnetic resonance was used to measure the self-diffusion coefficients. Structure and mobility properties of PEO were measured with differential scanning calorimetry as well as with positron annihilation lifetime spectroscopy. The largest reduction of the degree of crystallinity of PEO was observed when ww was increased from 0.13 w/w to 0.50 w/w. Moreover, water induced relaxation of the PEO segments in the amorphous phase, which seemed to have been strained by the crystals during compression molding. The water self-diffusion coefficient increased logarithmically with increased water content below water weight fractions in the amorphous phase of 0.30 w/w and the water molecules were obstructed by the crystalline phase.
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| 5. |
- Trotzig, Charlotte, et al.
(author)
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Transport properties of water in hydroxypropyl methylcellulose
- 2009
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In: European Polymer Journal. - : Elsevier BV. - 0014-3057. ; 45:10, s. 2812-2820
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Journal article (peer-reviewed)abstract
- The relation between the self-diffusion coefficient, D-self, of water and the free volume hole size, V-h, has been investigated in a hydroxypropyl methylcellulose (HPMC)-water system in the water content range 0.08-0.36 w/w, at room temperature. Furthermore, the thermal properties of the water in the HPMC-water system, as measured with differential scanning calorimetry (DSC) and the tensile storage, E', and tensile loss, E '', moduli, of the HPMC-water systems, as determined with dynamic mechanical analysis (DMA), have been probed. Pulsed-field gradient nuclear magnetic resonance (PFG NMR) was used to measure the D-self of water and positron annihilation lifetime spectroscopy (PALS) was used to measure the ortho-Positronium (o-Ps) lifetime in the HPMC-water system. The glass transition temperature of the HPMC was found to be reduced by the water to room temperature in the water content range 0.10-0.15 w/w. The relation between ln D-self of water and the inverse free volume hole size of the HPMC-water system was non-linear. Furthermore, the PALS measurements showed that molecular water co-existed with water clusters in the HPMC-water system. (C) 2009 Elsevier Ltd. All rights reserved.
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| 6. |
- Viridén, Anna, 1977, et al.
(author)
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Influence of Substitution Pattern on Solution Behavior of Hydroxypropyl Methylcellulose
- 2009
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In: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 10:3, s. 522-529
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Journal article (peer-reviewed)abstract
- Industrially produced hydroxypropyl Me cellulose (HPMC) is a chem. heterogeneous material, and it is thus difficult to predict parameters related to function on the basis of the polymer's av. chem. values. In this study, the soln. behavior of 7 HPMC batches was correlated to the mol. wt., degree of substitution, and substituent pattern. The initial onset of phase sepn., so-called clouding, generally followed an increased av. mol. wt. and degree of substitution. However, the slope of the clouding curve was affected by the substitution pattern, where the heterogeneously substituted batches had very shallow slopes. Further investigations showed that the appearance of a shallow slope of the clouding curve was a result of the formation of reversible polymer structures, formed as a result of the heterogeneous substituent pattern. These structures grew in size with temp. and concn. and resulted in an increase in the viscosity of the solns. at higher temps.
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