TY - JOUR

T1 - An investigation of drug compact topography as relates to intrinsic dissolution rates determined by dissolution imaging

AU - Brown, Benedict

AU - Fazili, Zayeem

AU - Ward, Adam

AU - Walton, Karl

AU - Blunt, Liam

AU - Østergaard, Jesper

AU - Asare-Addo, Kofi

PY - 2021

Y1 - 2021

N2 - The purpose of this study was to characterize compact surfaces (surface roughness) and study its potential importance to the intrinsic dissolution rate (IDR) as determined by dissolution imaging. To this end, the effect of varying compaction pressures and the use of two stainless-steel surfaces with different textures/roughness on the intrinsic dissolution were investigated. Ketoprofen (KET), paracetamol (PAR) and ibuprofen (IBU) were compacted and a focus variation microscope used to determine the surface topology of the compacts. IDR determination was conducted using a surface dissolution imaging apparatus with the flow-through set up in phosphate buffer at pH 7.2 and at 37 °C. The results indicated a general decrease in the surface area of the drug compacts with an increase in compaction force (p values < 0.05 for IBU and PAR but not KET). This change in surface area was measured using the Sdr parameter, which can be defined as the developed interfacial area. The smoother stainless-steel plate insert produced significantly smoother compacts for KET (Sdr decreased from 0.30% to 0.07%). However, PAR and IBU compacts showed an increase in their Sdr values from 3.94% to 17.90% and from 0.60% to 0.83%, respectively, suggesting the changes in surface properties to be drug specific relating to poor compaction properties and elasticity. The dissolution studies suggested that low compaction forces were not suitable for PAR. Overall changes in the surface topology did not have a significant effect on the obtained IDR values.

AB - The purpose of this study was to characterize compact surfaces (surface roughness) and study its potential importance to the intrinsic dissolution rate (IDR) as determined by dissolution imaging. To this end, the effect of varying compaction pressures and the use of two stainless-steel surfaces with different textures/roughness on the intrinsic dissolution were investigated. Ketoprofen (KET), paracetamol (PAR) and ibuprofen (IBU) were compacted and a focus variation microscope used to determine the surface topology of the compacts. IDR determination was conducted using a surface dissolution imaging apparatus with the flow-through set up in phosphate buffer at pH 7.2 and at 37 °C. The results indicated a general decrease in the surface area of the drug compacts with an increase in compaction force (p values < 0.05 for IBU and PAR but not KET). This change in surface area was measured using the Sdr parameter, which can be defined as the developed interfacial area. The smoother stainless-steel plate insert produced significantly smoother compacts for KET (Sdr decreased from 0.30% to 0.07%). However, PAR and IBU compacts showed an increase in their Sdr values from 3.94% to 17.90% and from 0.60% to 0.83%, respectively, suggesting the changes in surface properties to be drug specific relating to poor compaction properties and elasticity. The dissolution studies suggested that low compaction forces were not suitable for PAR. Overall changes in the surface topology did not have a significant effect on the obtained IDR values.

KW - Ketoprofen

KW - Paracetamol

KW - Ibuprofen

KW - Intrinsic dissolution rate

KW - UV-Imaging

KW - Focus variation microscopy

KW - Dissolution imaging

U2 - 10.1016/j.jddst.2020.102143

DO - 10.1016/j.jddst.2020.102143

M3 - Journal article

VL - 61

JO - Journal of Drug Delivery Science and Technology

JF - Journal of Drug Delivery Science and Technology

SN - 1773-2247

M1 - 102143

ER -