Biopharmaceutical implications of excipient variability on drug dissolution from immediate release products
| Autor: | James Mann, Elizabeth Meehan, Panagiota Zarmpi, Talia Flanagan, Nikoletta Fotaki, Jesper Østergaard |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Drug
media_common.quotation_subject Chemistry Pharmaceutical Excipient Pharmaceutical Science In vitro drug dissolution 02 engineering and technology Magnesium stearate 030226 pharmacology & pharmacy Excipients 03 medical and health sciences chemistry.chemical_compound Viscosity 0302 clinical medicine HPMC medicine Dissolution testing Solubility Multivariate data analysis Dissolution Sodium starch glycolate media_common Biological Products Chromatography Excipient variability General Medicine 021001 nanoscience & nanotechnology Drug Liberation Carbamazepine chemistry Particle size 0210 nano-technology Stearic Acids medicine.drug Tablets Biotechnology |
| Zdroj: | Zarmpi, P, Flanagan, T, Meehan, E, Mann, J, Østergaard, J & Fotaki, N 2020, ' Biopharmaceutical implications of excipient variability on drug dissolution from immediate release products ', European Journal of Pharmaceutics and Biopharmaceutics, vol. 154, pp. 195-209 . https://doi.org/10.1016/j.ejpb.2020.07.014 |
| DOI: | 10.1016/j.ejpb.2020.07.014 |
| Popis: | Elucidating the impact of excipient variability on oral product performance in a biopharmaceutical perspective would be beneficial and allow excipient implementation on Quality by Design (QbD) approaches. The current study investigated the impact of varying viscosity of binders (hypromellose (HPMC)) and superdisintegrants (sodium starch glycolate (SSG)) and particle size distribution of lubricants (magnesium stearate (MgSt)) on the in vitro dissolution of a highly and a poorly soluble drug from immediate release formulations. Compendial (pharmacopoeia buffers) and biorelevant (media simulating the gastrointestinal fluids) media and the USP 2 and USP 4 apparatuses were used to assess the exerted excipient effects on drug dissolution. Real-time dissolution UV imaging provided mechanistic insights into disintegration and dissolution of the immediate release formulations. Varying the viscosity type of HPMC or SSG did not significantly affect drug dissolution irrespective of the compound used. Faster drug dissolution was observed when decreasing the particle size of MgSt for the highly soluble drug. The use of real-time dissolution UV Imaging revealed the influential role of excipient variability on tablet disintegration, as for the highly soluble drug, tablets containing high viscosity HPMC or low particle size MgSt disintegrated faster as compared to the control tablets while for the poorly soluble drug, slower tablet disintegration was observed when increasing the viscosity of the HPMC as compared to the control tablets. Changes in drug dissolution when varying excipients may be anticipated if the excipient change has previously affected drug solubility. The use of multivariate data analysis revealed the influential biopharmaceutical factors such as critical excipient types/properties, drug aqueous solubility, medium/hydrodynamic characteristics affecting the impact of excipient variability on in vitro drug dissolution. |
| Databáze: | OpenAIRE |
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