Abstract
Purpose
This poster describes recent work within the European funded OrBiTo project on the dissolution behaviour of BCS Class II (poorly soluble) compounds using disk and powder methods and the impact of different media on the dissolution performance.
Methods
All compounds were supplied by EFPIA (European Federation of Pharmaceutical Industries and Associations) members of the OrBiTo project and used directly as powders or prepared as 3mm diameter disks using a tablet press with 80 kg load force. The compounds were all BCS Class II covering a range of acidic, basic and neutral functionality. Dissolution media consisted of pH6.5 phosphate or pH6.6 morpholinoethanesulfonic acid buffer, pH6.5 Fasted State Simulated Intestinal Fluid (FaSSIF) v1 and pH6.6 “Copenhagen FaSSIF”. Copenhagen FaSSIF contains different levels of bile salt:phospholipid as compared to FaSSIF v1. Dissolution measurements were performed using the SiriusT3 platform with built-in pH control and UV fibre-optic spectroscopy. UV-visible absorption spectra were recorded via a fibre-optic dip probe with a diode array spectrophotometer at fixed intervals for a specified period.
Results
Dissolution performance was found to link highly with the overall charge state of the compounds under study. Thus,
compounds with acidic or basic functionality would have good dissolution performance if significantly charged at the
measurement pH. Examples included ibuprofen and valsartan. The use of simulated intestinal fluid increased dissolution and solubility by as much as ten-fold for some compounds. Compounds that showed the largest increases in dissolution performance in SIF included Zafirlukast (acid), Bromocriptine (base) and Felodipine (neutral). Challenges relating to disk dissolution were weak UV absorbance associated with low concentrations in solution. Powder
dissolution experiments increased the UV absorbance levels compared to disk experiments but overall dissolution rates
depended on the sample weight used due to an increase in surface area. In order to determine intrinsic dissolution rates from powder it was necessary to correct the results for particle size.
Conclusion
Experimental protocols have been optimised to successfully determine dissolution profiles using small quantities of material. The results of the study reveal increased dissolution performance in the presence of simulated intestinal fluids compared to aqueous buffer systems for most of the BCS Class II compounds.
This poster describes recent work within the European funded OrBiTo project on the dissolution behaviour of BCS Class II (poorly soluble) compounds using disk and powder methods and the impact of different media on the dissolution performance.
Methods
All compounds were supplied by EFPIA (European Federation of Pharmaceutical Industries and Associations) members of the OrBiTo project and used directly as powders or prepared as 3mm diameter disks using a tablet press with 80 kg load force. The compounds were all BCS Class II covering a range of acidic, basic and neutral functionality. Dissolution media consisted of pH6.5 phosphate or pH6.6 morpholinoethanesulfonic acid buffer, pH6.5 Fasted State Simulated Intestinal Fluid (FaSSIF) v1 and pH6.6 “Copenhagen FaSSIF”. Copenhagen FaSSIF contains different levels of bile salt:phospholipid as compared to FaSSIF v1. Dissolution measurements were performed using the SiriusT3 platform with built-in pH control and UV fibre-optic spectroscopy. UV-visible absorption spectra were recorded via a fibre-optic dip probe with a diode array spectrophotometer at fixed intervals for a specified period.
Results
Dissolution performance was found to link highly with the overall charge state of the compounds under study. Thus,
compounds with acidic or basic functionality would have good dissolution performance if significantly charged at the
measurement pH. Examples included ibuprofen and valsartan. The use of simulated intestinal fluid increased dissolution and solubility by as much as ten-fold for some compounds. Compounds that showed the largest increases in dissolution performance in SIF included Zafirlukast (acid), Bromocriptine (base) and Felodipine (neutral). Challenges relating to disk dissolution were weak UV absorbance associated with low concentrations in solution. Powder
dissolution experiments increased the UV absorbance levels compared to disk experiments but overall dissolution rates
depended on the sample weight used due to an increase in surface area. In order to determine intrinsic dissolution rates from powder it was necessary to correct the results for particle size.
Conclusion
Experimental protocols have been optimised to successfully determine dissolution profiles using small quantities of material. The results of the study reveal increased dissolution performance in the presence of simulated intestinal fluids compared to aqueous buffer systems for most of the BCS Class II compounds.
| Original language | English |
|---|---|
| Number of pages | 1 |
| Publication status | Published - 2 Nov 2014 |
| Event | American Association of Pharmaceutical Scientists - San Diego, Arlington, United States Duration: 2 Nov 2014 → 6 Nov 2014 |
Conference
| Conference | American Association of Pharmaceutical Scientists |
|---|---|
| Country/Territory | United States |
| City | Arlington |
| Period | 2/11/14 → 6/11/14 |
Keywords
- powder dissolution experiments
- BCS Class II (poorly soluble) compounds
- dissolution performance.