The Combined Use of Imaging Approaches to Assess Drug Release from Multicomponent Solid Dispersions

Abstract

PurposeImaging methods were used as tools to provide an understanding of phenomena that occur during dissolution experiments, and ultimately to select the best ratio of two polymers in a matrix in terms of enhancement of the dissolution rate and prevention of crystallization during dissolution.MethodsMagnetic resonance imaging, ATR-FTIR spectroscopic imaging and Raman mapping have been used to study the release mechanism of a poorly water soluble drug, aprepitant, from multicomponent amorphous solid dispersions. Solid dispersions were prepared based on the combination of two selected polymers - Soluplus, as a solubilizer, and PVP, as a dissolution enhancer. Formulations were prepared in a ratio of Soluplus:PVP 1:10, 1:5, 1:3, and 1:1, in order to obtain favorable properties of the polymer carrier.ResultsThe crystallization of aprepitant during dissolution has occurred to a varying degree in the polymer ratios 1:10, 1:5, and 1:3, but the increasing presence of Soluplus in the formulation delayed the onset of crystallization. The Soluplus:PVP 1:1 solid dispersion proved to be the best matrix studied, combining the abilities of both polymers in a synergistic manner.ConclusionsAprepitant dissolution rate has been significantly enhanced. This study highlights the benefits of combining imaging methods in order to understand the release process.Electronic supplementary materialThe online version of this article (doi:10.1007/s11095-016-2018-x) contains supplementary material, which is available to authorized users.

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

“…Ninety-two of the 101 studies reported solubility and dissolution studies ( 71 – 74 , 77 – 79 , 81 – 92 , 95 , 97 – 107 , 109 – 111 , 113 – 119 , 121 , 123 , 124 , 126 – 133 , 135 – 139 , 141 – 154 , 156 , 157 , 160 , 161 , 166 , 168 – 176 ). The USP in vitro dissolution type II apparatus was the most commonly used instrument (67%), followed by the USP type I apparatus (6%), while the remaining 27% used various other apparatuses, including modified versions of the USP type I only ( 148 ) or paired with confocal Raman microscopy ( 98 ), USP types I and II apparatus ( 72 ), USP type IV ( 152 ), closed loop of USP types II and IV ( 152 ), a perspex flow cell ( 73 , 142 ), a rotary mixer ( 131 ), a Chinese pharmacopoeia type III apparatus ( 118 ), an in-house miniaturized USP type II apparatus ( 175 ), Sirius T3 apparatus ( 146 ), μFLUX dissolution-permeation apparatus ( 141 ), Raman UV-Vis flow cell system ( 99 ), a centrifuge ( 88 ), high throughput screening using a 96-well plate ( 82 , 115 , 157 ), Wood’s apparatus ( 99 , 137 ), an orbital shaking incubator ( 156 ), and another shake-flask method ( 171 ) (Fig. 6 ).…”

“…6 ). In several of these studies, dissolution apparatuses were either modified, optimized or paired with other instruments and methods to enable the investigation, monitoring, and understanding of other processes that take place concurrently with dissolution such as permeation ( 141 ), release mechanisms ( 73 , 98 , 99 , 101 , 106 , 142 ) and wetting kinetics ( 71 ). The experimental conditions during in vitro dissolution testing (e.g.…”

Hot Melt Extrudates Formulated Using Design Space: One Simple Process for Both Palatability and Dissolution Rate Improvement

“…29 In the present study, these different mechanisms act together to improve ITZ dissolution and may be the reason why the combination of the polymers has led to a better drug dissolution. 30 In Vitro Taste-Masking Evaluation E-tongue sensors imitate taste bud on human tongue by initiating changes in electric potentials that can be compared to physiological action. 31 This in vitro assay presents a high correlation with human sensory test and is until 100 times more sensitive for bitter taste than human panel.…”

Oral Drug Delivery Systems Based on Ordered Mesoporous Silica Nanoparticles for Modulating the Release of Aprepitant

“…In this context, the development of novel formulations containing aprepitant that may enhance its solubility and bioavailability is considered of great importance for the reduction of the required dose [8,12,13]. A broad range of methods have been proposed for co-formulating aprepitant with different carriers for oral delivery, including micro-emulsions [14,15], self-emulsified drug delivery systems (SEDDS) [16], solid dispersions [17][18][19][20][21], hot-melt extrusion [18], liquisolid formulations [22], and inclusion complexes (cyclodextrins) [13,23].…”

“…A broad range of methods have been proposed for co-formulating aprepitant with different carriers for oral delivery, including micro-emulsions [ 14 , 15 ], self-emulsified drug delivery systems (SEDDS) [ 16 ], solid dispersions [ 17 , 18 , 19 , 20 , 21 ], hot-melt extrusion [ 18 ], liquisolid formulations [ 22 ], and inclusion complexes (cyclodextrins) [ 13 , 23 ].…”