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- Sinko, Patrick D., et al.
(författare)
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Ultrathin, Large-Area Membrane Diffusion Cell for pH-Dependent Simultaneous Dissolution and Absorption Studies
- 2020
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Ingår i: Molecular Pharmaceutics. - : AMER CHEMICAL SOC. - 1543-8384 .- 1543-8392. ; 17:7, s. 2319-2328
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical evaluation of modern oral dosage forms requires more advanced in vitro devices as the trend of selecting low solubility, high permeability compounds for commercial development continues. Current dissolution methodologies may not always be suitable for such compounds due to excessive fluid volume, high fluid shear rates, heterogeneity of shear rates, suboptimal fluid flow, and, ultimately, the lack of absorption ability (Gray et al. The Science of USP 1 and 2 Dissolution: Present Challenges and Future Relevance; Pharmaceutical Research, 2009; Vol. 26; pp 1289-1302). Herein, a new dissolution apparatus is introduced in combination with an ultrathin, semipermeable polymer membrane that mimics human passive absorption for lipophilic compounds. The ultrathin large-area polydimethylsiloxane (PDMS) membrane (UTLAM) absorption system is designed to mimic the dissolution and passive transcellular diffusion process representing the oral absorption pathway. A simple spin-casting method was developed to fabricate the ultrathin highly uniform membranes. To minimize membrane resistance to diffusion and maximize transport across the polymer membrane, 10-40 mu m PDMS membranes were successfully prepared. A new diffusion cell was designed and tested to support the UTLAM and incorporates a hydrofoil impeller for more desirable hydrodynamics and mixing, using ibuprofen as a model weak acidic drug. UTLAM permeability was sufficiently high that the aqueous boundary layer contributed to the overall permeability of the system. This diffusion cell system demonstrated that, when the aqueous diffusion layer contributes to the overall resistance to transport, the pH at which absorption is 50% of maximum (pH(50)(%)) shifts from the pK(a) to higher values, demonstrating why weak acid drugs can exhibit high absorption at pH's significantly greater than their pK(a). High rates of transport across the UTLAM are possible for drugs with high partition coefficients (i.e., BCS II compounds even under mostly ionized conditions), and PDMS UTLAMs may be tailored to simulate human intestinal passive absorption rates.
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| 2. |
- Villamil Velasquez, Carolina, et al.
(författare)
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HOW CAN INFORMATION and COMMUNICATIONS TECHNOLOGY SUPPORT the LINK between CIRCULAR ECONOMY and PRODUCT LIFE CYCLE MANAGEMENT?- A REVIEW
- 2020
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Ingår i: Proceedings of the Design Society. - : Cambridges Institutes Press. - 2633-7762. ; , s. 2187-2196
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Konferensbidrag (refereegranskat)abstract
- Linear production is related to resource scarcity and negative environmental impacts. Circular Economy (CE) emerged for society transition towards sustainability, based on regenerative systems and multiple life cycle products. Product Life cycle Management (PLM) supports the whole life cycle with the aid of Information and Communication Technology (ICT). A literature review analyzed the role of ICT enabling CE based on PLM, identifying challenges and opportunities, active and passive PLM, system perspective, stakeholder's role, and sustainability. Concluding that ICT enables the CE transition. © The Author(s), 2020. Published by Cambridge University Press.
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