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- 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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| 14. |
- Caccavo, D., et al.
(författare)
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Mathematical modelling of the drug release from an ensemble of coated pellets
- 2017
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Ingår i: British Journal of Pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 174:12, s. 1797-1809
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Tidskriftsartikel (refereegranskat)abstract
- Background and PurposeCoated pellets are widely used as oral drug delivery systems, being highly accepted by patients and with several advantages compared to single unit devices. However, their behaviour needs to be elucidated so as to improve the effectiveness of the formulations and reduce production costs. In spite of this important issue, few mathematical modelling studies have been attempted, mostly due to the complexities arising from the system's polydispersity (non-homogeneous multiple-unit particulate systems), which has been scarcely investigated using mechanistic models. Experimental approachA mechanistic mathematical model was developed that was able to describe the single pellet behaviour in terms of hydration, drug dissolution, diffusion and release and particle size. This model was then extended to describe and predict the behaviour of mono- and polydispersed ensembles of pellets. Key ResultsThe polydispersity arising from the size and distribution of the inert core was shown to have a minimal effect on the drug release profile, whereas the thickness and distribution of the polymeric film was found to be the key parameter determining the drug release. Conclusions and ImplicationsThe mechanistic model developed, which is capable of determining the polydispersity of the drug delivery system, was able to predict the release kinetics from ensembles of pellets and to highlight the key parameters that need to be controlled in the production of pellet-based drug delivery systems, demonstrating its use as a powerful predictive tool.
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| 15. |
- Caccavo, D., et al.
(författare)
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Modeling the mechanics and the transport phenomena in hydrogels
- 2018
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Ingår i: Computer Aided Chemical Engineering. - 1570-7946. ; 42, s. 357-383
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Hydrogels are polymeric materials widely used in pharmaceutical and biomedical applications. Their uses can be improved by modeling their behavior, in particular the mechanical phenomena and the transport phenomena. The scope of this chapter is to propose a model, simple enough and with a limited number of parameters to be determined, able to capture the full behavior of a swelling hydrogel, with the aim of describing the drug release process as well as—in principle—any other application of hydrogels. The model was derived recalling the basics of the continuum mechanics, the possible approaches to estimate the Helmholtz free energy, and then writing the transport and constitutive equations for a poroelastic material, and for a more realistic poroviscoelastic material (by adding the standard linear solid model as the rheological model). A full extension to multicomponent systems, to describe the drug release phenomenon, is proposed along with a sensitivity analysis (free-swelling simulation by changing the model parameters).
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| 16. |
- Caccavo, D., et al.
(författare)
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Understanding the adhesion phenomena in carbohydrate-hydrogel-based systems: Water up-take, swelling and elastic detachment
- 2015
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Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617. ; 131, s. 41-49
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Tidskriftsartikel (refereegranskat)abstract
- The bio-adhesion is a complex phenomenon which takes place when two materials (at least one of biological nature, the other usually is a polymeric one) are held together for extended periods of time, usually for local drug delivery purposes. Despite bio-adhesion is widely exploited in commercial pharmaceuticals such as the buccal patches, the underlying phenomena of the process are not completely clarified yet. In this study experimental tests, in which the role of biological membranes is played by a water-rich agarose gel whereas patches are mimicked by hydrogel tablets (made of Carbopol or of Carbopol added with NaCl), have been used to analyze the behavior of the model system above described. Tablets have been forced to adhere on the agarose gel, and after a given contact time they have been detached, recording the required forces. Furthermore weight gain of the tablets (the water transported from the agarose gel toward the tablet) has been quantified. Water transport (during the time in which the contact between tablet and agarose gel is held) and elastic part of mechanical response during the detachment are modelled to achieve a better understanding of the adhesion process. Both the two sub-models nicely reproduce, respectively, the weight gain as well as the swelling of the Carbopol tablets, and the point at which the mechanical response ceases to be purely elastic.
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| 17. |
- Kazlauske, Jurgita, 1981, et al.
(författare)
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Determination of the release mechanism of Theophylline from pellets coated with Surelease (R)-A water dispersion of ethyl cellulose
- 2017
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 528:1-2, s. 345-353
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the water transport over free standing films based on the aqueous ethyl cellulose (EC) coating Surelease (R) and the drug (Theophylline) release mechanism from coated pellets. It was found that the main drug release rate from pellets was controlled by a diffusion mechanism. However, the drug release rate was altered by addition of sodium chloride to the external release medium. A decrease in the drug release rate when sodium chloride is added to the release medium has traditionally been used to indicate an osmotic drug release mechanism. However, our findings that the release rate decreased by sodium chloride addition could be explained by sodium chloride diffusing through the coating layer into the inner parts of the pellets, decreasing the solubility of Theophylline. This gave a reduced drug concentration gradient over the coating layer and thus a slower release rate. Furthermore, this study shows, as expected, that the transport of water through Surelease (R) films into the pellets was faster than the transport out of Theophylline (approx. seven times), which was the reason why the pellets were swelling during the release. It was also shown that the drug release rate, determined for both whole dose release and for single pellets, decreased with increasing thickness (from 16 to 51 mm) of the coating layer controlling the drug release rate.
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