Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 195-209 |
| Number of pages | 15 |
| Journal | European Journal of Pharmaceutics and Biopharmaceutics |
| Volume | 154 |
| Early online date | 16 Jul 2020 |
| DOIs | |
| Publication status | Published - 1 Sept 2020 |
Funding
The authors would like to acknowledge AstraZeneca and the University of Bath for funding the current project. The authors would also like to acknowledge Jeff Parry for his work on the production of the studied batches and Søren Michael Nielsen for his work and help on real-time surface dissolution UV imaging experiments. Part of this work has been previously included in a poster at the AAPS Annual Meeting in Washington DC, USA, November 2018.
Keywords
- Excipient variability
- HPMC
- In vitro drug dissolution
- Magnesium stearate
- Multivariate data analysis
- Sodium starch glycolate
ASJC Scopus subject areas
- Biotechnology
- Pharmaceutical Science