Biomimetic Dissolution: A Tool to Predict Amorphous Solid Dispersion Performance

Abstract

The presented study describes the development of a membrane permeation non-sink dissolution method that can provide analysis of complete drug speciation and emulate the in vivo performance of poorly water-soluble Biopharmaceutical Classification System class II compounds. The designed membrane permeation methodology permits evaluation of free/dissolved/unbound drug from amorphous solid dispersion formulations with the use of a two-cell apparatus, biorelevant dissolution media, and a biomimetic polymer membrane. It offers insight into oral drug dissolution, permeation, and absorption. Amorphous solid dispersions of felodipine were prepared by hot melt extrusion and spray drying techniques and evaluated for in vitro performance. Prior to ranking performance of extruded and spray-dried felodipine solid dispersions, optimization of the dissolution methodology was performed for parameters such as agitation rate, membrane type, and membrane pore size. The particle size and zeta potential were analyzed during dissolution experiments to understand drug/polymer speciation and supersaturation sustainment of felodipine solid dispersions. Bland-Altman analysis was performed to measure the agreement or equivalence between dissolution profiles acquired using polymer membranes and porcine intestines and to establish the biomimetic nature of the treated polymer membranes. The utility of the membrane permeation dissolution methodology is seen during the evaluation of felodipine solid dispersions produced by spray drying and hot melt extrusion. The membrane permeation dissolution methodology can suggest formulation performance and be employed as a screening tool for selection of candidates to move forward to pharmacokinetic studies. Furthermore, the presented model is a cost-effective technique.

Plasma modification of microporous polymer membranes for application in biomimetic dissolution studies

“…Observations suggest fluorination as a more effective and less destructive treatment technique. Dissolution testing was used to compare treated membranes with porcine intestines (Puppolo et al 2017). Dissolution results indicated that CF 4 plasma treated PES membranes with a pore size of 0.1 μm exhibited similar transport properties when compared to porcine intestines.…”

“…In a supplemental study, a detailed comparison of the CF 4 plasma treated polymer membranes and porcine intestines is presented by Puppolo et al (Puppolo et al 2017). This work demonstrates the biomimetic nature of the plasma treated polymer membranes by evaluating multiple statistical relationships, including Bland-Altman analysis and correlation coefficients (Puppolo et al 2017). It should be noted that of the four membrane modifications investigated (H 2 O, DCM, C 6 F 14 , CF 4 ), only CF 4 plasma treated membranes provided reproducible dissolution performance.…”

“…It should be noted that of the four membrane modifications investigated (H 2 O, DCM, C 6 F 14 , CF 4 ), only CF 4 plasma treated membranes provided reproducible dissolution performance. Following a comprehensive assessment of the dissolution performance (area under the dissolution curve and flux values) for CF 4 plasma treated nylon and PES membranes relative to porcine intestines, PES membranes with a pore size of 0.1 μm were employed for a comparison of hot melt extruded and spray dried Felodipine solid dispersions (Puppolo et al 2017). The supplemental work presented by Puppolo et al illustrates the utility of CF 4 plasma treated membranes in a membrane-permeation dissolution experiment (Puppolo et al 2017).…”

“…Although a number of applications exist for plasma treated microporous polymer membranes, they have not been extensively studied as a platform for biomimetic membranes in dissolution testing. Plasma modifications can be manipulated to produce biomimetic polymer membranes that act as a surrogate for the intestinal membrane, thus tailoring their application for dissolution testing (Puppolo et al 2017). A schematic showing the biomimetic membranes in an experimental permeation/ dissolution chamber that exploits the amphipathic nature of the membrane is presented in Fig.…”

In Vitro–In Vivo Correlations of Carbamazepine Nanodispersions for Application in Formulation Development

“…These systems allow adjustment of the dissolution media, the membrane for permeation, the agitation during the dissolution process as well as the acceptor sink solution, making it a versatile system for relating to in vivo absorption of many different drugs and dosage forms. 44 The usefulness of membranepermeation dissolution systems has been demonstrated by establishing IVIVC in multiple studies. 31,45,46 Microcentrifuge and ultrafiltration dissolution techniques depicted the disconnect between the in vitro tests and in vivo results was due to more than the measurement of the free drug concentration alone, thereby suggesting the need for a system which would not only assess free drug concentrations but also consider the diffusion of a drug across a membrane.…”