| 1. |
- Gårdebjer, Sofie, 1985, et al.
(författare)
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The impact of interfaces in laminated packaging on transport of carboxylic acids
- 2016
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Ingår i: Journal of Membrane Science. - : Elsevier BV. - 0376-7388 .- 1873-3123. ; 518, s. 305-312
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Tidskriftsartikel (refereegranskat)abstract
- The permeability of oleic and acetic acid through low density polyethylene (LDPE) and ethylene acrylic acid (EAA) have been measured using diffusion cells. In addition, the permeability through combinations of LDPE and EAA in the form of laminates with different numbers of layers has been determined. Oleic acid shows an almost 30 times higher permeability compared to acetic acid, which was partly explained by the adsorption of oleic acid to the film surface during the permeability experiment. In addition, the permeability is lower for both oleic and acetic acid in the laminates compared to the pure films. The decreased permeability can be explained by the presence of crystalline domains close to the interface. This is supported by SAXS data which suggests an ordering of polymer chains in the EAA film close to the interface. In summary, the results show that it is possible to create barrier materials with decreased permeability, which is interesting for example in the packaging industry.
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| 2. |
- Caccavo, D., et al.
(författare)
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Effects of HPMC substituent pattern on water up-take, polymer and drug release: An experimental and modelling study
- 2017
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 528:1-2, s. 705-713
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the hydration behavior of two matrix formulations containing the cellulose derivative hydroxypropyl methylcellulose (HPMC). The two HPMC batches investigated had different substitution pattern along the backbone; the first one is referred to as heterogeneous and the second as homogenous. The release of both the drug molecule theophylline and the polymer was determined. Additionally, the water concentrations at different positions in the swollen gel layers were determined by Magnetic Resonance Imaging. The experimental data was compared to predicted values obtained by the extension of a mechanistic Fickian based model. The hydration of tablets containing the more homogenous HPMC batch showed a gradual water concentration gradient in the gel layer and could be well predicted. The hydration process for the more heterogeneous batch showed a very abrupt step change in the water concentration in the gel layer and could not be well predicted. Based on the comparison between the experimental and predicted data this study suggests, for the first time, that formulations with HPMC of different heterogeneities form gels in different ways. The homogeneous HPMC batch exhibits a water sorption behavior ascribable to a Fick's law for the diffusion process whereas the more heterogeneous HPMC batches does not. This conclusion is important in the future development of simulation models and in the understanding of drug release mechanism from hydrophilic matrices.
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| 3. |
- Deshmukh, Shivprasad, et al.
(författare)
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Injection moulded controlled release amorphous solid dispersions: Synchronized drug and polymer release for robust performance
- 2020
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 575
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Tidskriftsartikel (refereegranskat)abstract
- A study has been carried out to investigate controlled release performance of caplet shaped injection moulded (IM) amorphous solid dispersion (ASD) tablets based on the model drug AZD0837 and polyethylene oxide (PEO). The physical/chemical storage stability and release robustness of the IM tablets were characterized and compared to that of conventional extended release (ER) hydrophilic matrix tablets of the same raw materials and compositions manufactured via direct compression (DC). To gain an improved understanding of the release mechanisms, the dissolution of both the polymer and the drug were studied. Under conditions where the amount of dissolution media was limited, the controlled release ASD IM tablets demonstrated complete and synchronized release of both PEO and AZD0837 whereas the release of AZD0837 was found to be slower and incomplete from conventional direct compressed ER hydrophilic matrix tablets. The results clearly indicated that AZD0837 remained amorphous throughout the dissolution process and was maintained in a supersaturated state and hence kept stable with the aid of the polymeric carrier when released in a synchronized manner. In addition, it was found that the IM tablets were robust to variation in hydrodynamics of the dissolution environment and PEO molecular weight.
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| 4. |
- Larsson, Mikael, 1982, et al.
(författare)
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The influence of HPMC substitution pattern on solid state properties
- 2010
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Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617 .- 1879-1344. ; 82:4, s. 1074-1081
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Tidskriftsartikel (refereegranskat)abstract
- The solid-state properties were studied for different batches of hydroxypropyl methylcellulose (HPMC). The batches had similar chemical composition, but different degree of heterogeneity with regard to the distribution of the substituents along the polymer chains. The glass transition temperature, Tg, was analysed using a new developed method where dynamic mechanic analysis, DMA, was performed in compression mode on compacts, utilizing a wedge-shaped probe. The method was verified by conventional DMA on films. Molecular interactions were studied using FT-IR. In addition, the water vapour sorption was determined by gravimetric measurements and the plasticization by water vapour was studied on film samples using DMA. The results revealed a linear relationship between increasing Tg and increasing percent glucose liberated after enzyme hydrolysis. The percent glucose liberated can in turn be considered to account for both the heterogeneity of the substituents and the total degree of substitution. The results indicated that more heterogeneously substituted cellulose derivatives and derivates with a lower degree of substitution had stronger interactions between polymer chains. As expected from these results, some small difference in the plasticization by water vapour could be detected. However, no significant differences were found in molecular interactions using FT-IR or in the sorption of water vapour. The correlation between heterogeneity in the distribution of the substituents and Tg is of much interest as heterogeneously substituted batches of HPMC have been previously shown to exhibit very different behaviour in solution and in gelling tablets.
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| 5. |
- Viridén, Anna, 1977, et al.
(författare)
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Influence of Substitution Pattern on Solution Behavior of Hydroxypropyl Methylcellulose
- 2009
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 10:3, s. 522-529
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Viridén, Anna, 1977, et al.
(författare)
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Investigation of critical polymer properties for polymer release and swelling of HPMC matrix tablets
- 2009
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 36:2-3, s. 297-309
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Tidskriftsartikel (refereegranskat)abstract
- Four different HPMC batches were characterized to investigate properties related to crit. functionality for their use in hydrophilic matrix tablets. In this study, the HPMC batches were chem. characterized and correlated to the behavior of pure HPMC tablets. Parameters such as the mol. wt., viscosity, intrinsic viscosity and radius of gyration were kept in a rather limited range, which resulted in a weak correlation to polymer release and degree of swelling. The hydrophilic/hydrophobic character of the HPMC samples was elucidated by the degree of substitution and by the clouding behavior, where an increased hydrophilicity increased the tablet swelling. This phenomenon was interpreted in a refined model for water transport into HPMC tablets. A five times slower polymer release and a considerably larger degree of swelling were found for one batch of HPMC tablets compared to the others, although the characterized av. polymer parameters were in the same range. However, the conformation plot displayed a fraction with compact aggregates. In conclusion, the existence of aggregates in aq. soln. seems to perturb the functionality of HPMC tablets and it seems important to understand and characterize these aggregates to fully predict the polymer release and swelling of HPMC tablets.
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| 7. |
- Viridén, Anna, 1977
(författare)
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Investigation of the functionality related characteristics of hydroxypropyl methylcellulose for the release from matrix tablets
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hydrophilic matrix tablets are a compressed well mixed composite of drug substance and excipients including a hydrophilic polymer. When the tablet comes in contact with biological fluids, the hydrophilic polymer starts to dissolve, a process that decreases the water penetration through the tablet and involves dimensional changes of the tablet due to swelling of the solvated polymers. At a certain dilution the polymer will erode from the surface and the tablet will eventually dissolve. The processes involving tablet hydration, swelling and erosion will affect the drug release from the matrix and are all related to the polymer properties. Thus, to formulate robust matrices with predictable drug release rates and mechanisms, functionality related parameters, FRCs, of the polymers must be known and controlled. Hydroxypropyl methylcellulose, HPMC, is one of the most commonly used polymers in hydrophilic matrix tablets. However, HPMC is a heterogeneous material in both size and chemical substitution and hence the known FRCs have not always shown to be sufficient for the prediction of drug release from hydrophilic matrix tablets. The aim of the present thesis has therefore been to characterise additional FRCs for the drug release from matrix tablets. With the use of endoglucanases, which selectively catalyse the hydrolysis of the cellulose backbone, differences were found in substituent heterogeneity between HPMC batches of the same commercial grades. These structural differences were related to their properties in solution and their behaviour in hydrophilic matrix tablets. It was found that the more heterogeneously substituted HPMC batches obtained more amphiphilic behaviour, where transient hydrophobic interactions between the more highly substituted regions were formed in solution. These interactions increased with temperature and HPMC concentration and they gave rise to slower polymer erosion and increased swelling of the tablets. Consequently, the drug release was highly affected by the substituent heterogeneity of the polymers in the matrices. In addition, it was found that, dependent on the polymer structure, the polymer-drug interactions affected the robustness, i.e. tablet erosion rate, to different extents. The conclusion drawn in the present thesis is therefore that the substituent heterogeneity of HPMC should be regarded as an FRC for drug release from matrix tablets.
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| 8. |
- Viridén, Anna, 1977, et al.
(författare)
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Model drug release from matrix tablets composed of HPMC with different substituent heterogeneity
- 2010
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 401:1-2, s. 60-67
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Tidskriftsartikel (refereegranskat)abstract
- The release of a model drug substance, methylparaben, was studied in matrix tablets composed of hydroxypropyl methylcellulose (HPMC) batches of the USP 2208 grade that had different chemical compositions. It was found that chemically heterogeneous HPMC batches with longer sections of low substituted regions and lower hydroxypropoxy content facilitated the formation of reversible gel structures at a temperature as low as 37 degrees C. Most importantly, these structures were shown to affect the release of the drug from matrix tablets, where the drug release decreased with increased heterogeneity and a difference in T80 values of 7 h was observed between the compositions. This could be explained by the much lower erosion rate of the heterogeneous HPMC batches, which decreased the drug release rate and also released the drug with a more diffusion based release mechanism compared to the less heterogeneous batches. It can therefore be concluded that the drug release from matrix tablets is very sensitive to variations in the chemical heterogeneity of HPMC.
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| 9. |
- Viridén, Anna, 1977, et al.
(författare)
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Release of theophylline and carbamazepine from matrix tablets - Consequences of HPMC chemical heterogeneity
- 2011
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Ingår i: European Journal of Mineralogy. - : Elsevier BV. - 0935-1221. ; 78:3, s. 470-479
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Tidskriftsartikel (refereegranskat)abstract
- The release of theophylline and carbamazepine from matrix tablets composed of microcrystalline cellulose, lactose and hydroxypropyl methylcellulose (HPMC) was studied. The aim was to investigate the effect of different substituent heterogeneities of HPMC on the drug release from matrix tablets composed of either 35% or 45% HPMC. The release of the poorly soluble carbamazepine was considerably affected by the HPMC heterogeneity, and the time difference at 80% drug release was more than 12 h between the formulations of different HPMC batches. This was explained by slower polymer erosion of the heterogeneous HPMC and the fact that carbamazepine was mainly released by erosion. In addition, results from magnetic resonance imaging showed that the rate of water transport into the tablets was similar. This explained the comparable results of the release of the sparingly soluble theophylline from the two formulations even though the polymer erosion and the swelling of the tablets were considerably different. Thus, it can be concluded that the drug release was highly affected by the substituent heterogeneity, especially in the case of carbamazepine, which was released mainly by erosion. (C) 2011 Elsevier B.V. All rights reserved.
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| 10. |
- Viridén, Anna, 1977, et al.
(författare)
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The consequence of the chemical composition of HPMC in matrix tablets on the release behaviour of model drug substances having different solubility
- 2011
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Ingår i: European Journal of Pharmaceutics and Biopharmaceutics. - : Elsevier BV. - 1873-3441 .- 0939-6411. ; 77:1, s. 99-110
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates the effect of the chemical heterogeneity of hydroxypropyl methylcellulose (HPMC) on the release of model drug substances from hydrophilic matrix tablets. The hypothesis was that the release of drug substances could be influenced by possible interactions with HPMC batches having different chemical heterogeneity. The cloud point of the most heterogeneous batch was more affected by the model drug substances, methylparaben and butylparaben, and most by butylparaben with the lowest solubility. The different clouding behaviour was explained by the heterogeneously substituted batches being more associative and the more lipophilic butylparaben being able to interact more efficiently with the hydrophobic HPMC transient crosslinks that formed. Interestingly, tablet compositions of the heterogeneously substituted HPMC batches released the more soluble methylparaben at lower rates than butylparaben. The explanation is that the hydrophobic HPMC interactions with butylparaben made the gel of the tablet less hydrated and more fragile and therefore more affected by erosional stresses. In contrast, drug release from compositions consisting of the more homogeneously substituted batches was affected to a minor extent by the drugs and was very robust within the experimental variations. The present study thus reveals that there can be variability in drug release depending on the lipophilicity of the drug and the substituent heterogeneity of the HPMC used.
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| 11. |
- Viridén, Anna, 1977, et al.
(författare)
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The effect of chemical heterogeneity of HPMC on polymer release from matrix tablets
- 2009
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Ingår i: European journal of pharmaceutical sciences official journal of the European Federation for Pharmaceutical Sciences. - : Elsevier BV. - 1879-0720. ; 36:4-5, s. 392-400
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Tidskriftsartikel (refereegranskat)abstract
- Polymer release from hydrophilic matrix tablets, composed of hydroxypropyl methylcellulose, was studied for seven different polymer batches. A time difference of more than 80h between fully dissolved tablets was noticed although the batches were of the same pharmaceutical substituent (USP 2208) and viscosity (100 cps) grade. To find the functionality related parameters for polymer release from hydrophilic matrix tablets the polymer samples were characterised according to size and chemical composition. The size of the polymers was characterised by size-exclusion chromatography with multi-angle light scattering and refractive index detection. The average amount of substituents was measured with nuclear magnetic resonance and the distribution of the substituents along the cellulose chain was determined with high-performance anion-exchange chromatography with pulsed amperometric detection after acid and enzymatic hydrolysis. The results indicated that other types of interactions apart from entanglements were present between the polymer chains, which seemed to affect the polymer release. Most importantly, this study has shown a correlation between the polymer release and the substituent pattern, where the samples with slow release also were more heterogeneously substituted along the polymer chain. From this we can conclude that polymer release is very sensitive to alterations in chemical composition.
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| 12. |
- Viridén, Anna, 1977, et al.
(författare)
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The effect of substitution pattern of HPMC on polymer release from matrix tablets
- 2010
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 389:1-2, s. 147-156
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to gain further understanding of how the substituent heterogeneity of hydroxypropyl methylcellulose, HPMC, affects the polymer release from hydrophilic matrix tablets. The hypothesis was that the heterogeneous substituent pattern facilitated hydrophobic interactions that increased the viscosity and therefore affected the release rate to a major extent. Polymer tablets were prepared from three heterogeneously substituted HPMC batches of the same substituent (2208) and viscosity (100 cps) grade. To elucidate the hypothesis, fractions of both the dissolved polymer and the tablet residue were collected from the dissolution bath and further characterised. The extensive characterisation showed that, although the dissolved bath fraction and the tablet residue had a similar average degree of substitution, the residue was more heterogeneously substituted. It was further revealed that the heterogeneous substituent pattern of the tablet residue facilitated the formation of soluble gel-like components already at room temperature, which increased the viscosity. The viscosity increased by 150% at temperatures correlated to the dissolution bath, and it was thus concluded that the gel-like components grew in size with temperature. Finally, much lower release rates were obtained by tablets composed of the residue compared to tablets composed of the bath fraction, which clarified the hypothesis.
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