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Amorphisation Behaviour of Fluefenamic Acid in Formulations with Cellulose
KTH, School of Chemical Science and Engineering (CHE).
2016 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesisAlternative title
Amorfisering av FFA i cellulosa formuleringar (Swedish)
Abstract [en]

Poor solubility and subsequent unsatisfactory dissolution rate of crystalline pharmaceutical ingredients compromise oral bioavailability and limit the commercialization of successful and effective drug formulations in the conventional route of oral administration. One of the basic approaches for solubility enhancement of poorly water-soluble drugs is amorphisation of the drug in solid dispersion with excipient materials. The anti-inflammatory drug, flufenamic acid (FFA), is an example of crystalline pharmaceutical ingredient that exhibit poor aqueous solubility. In this study, FFA was physically mixed with three different celluloses, i.e. microcrystalline cellulose (MCC), porous microcrystalline cellulose (P-MCC) and Cladophora cellulose to investigate the potential of cellulose-based excipient materials to stabilize the amorphous state of the drug. The mixtures were prepared in both heated and normal forms, where heat-treatment involved heating the samples to 120 °C for 2 hours. Physical and chemical properties of the mixtures were studied through a range of conventional analytical techniques, including differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, solid-state fluorescence and powder X-ray diffraction (XRD). The results suggest that FFA exists in an amorphous dispersion when heated in formulations with both Cladophora cellulose and P-MCC. The drug release behaviour of FFA from cellulose-drug formulations within a 5-hour timeframe were analysed through an in vitro dissolution study in simulated intestinal fluid. The data revealed an increase in the dissolution rate of FFA due to the pore-induced amorphisation in the heated formulations with Cladophora cellulose and P-MCC. Furthermore, stabilization and conservation of the amorphous state of incorporated drug was demonstrated in the heated formulation with P-MCC. The results suggest a promising approach in the development of solid-dosage formulations with P-MCC as the excipient material for solubility and ultimately bioavailability enhancement of crystalline pharmaceutical ingredients.

Place, publisher, year, edition, pages
2016.
Keyword [en]
Microcrystalline cellulose, Porous microcrystalline cellulose, Cladophora cellulose, Flufenamic Acid, Phase transition, Amorphisation.
National Category
Nano Technology Polymer Technologies
Identifiers
URN: urn:nbn:se:kth:diva-207031OAI: oai:DiVA.org:kth-207031DiVA: diva2:1095247
Available from: 2017-05-12 Created: 2017-05-12 Last updated: 2017-05-12Bibliographically approved

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  • apa
  • harvard1
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  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
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Output format
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