Impact of Molecular Partitioning and Partial Equilibration on the Estimation of Diffusion Coefficients from Release Experiments

Abstract

The present work addresses the effect of partial equilibration and molecular partitioning on the interpretation of release experiments. In this regard, it is shown how release profiles and the values of extracted transport parameters are affected by the time protocol chosen for sample collection by considering a series of experiments where the latter is systematically varied. Caffeine is investigated as a main model drug because of its similar affinity for water and lipids, while monolinolein-based lipid cubic phases are chosen as host matrices because of their wide employment in release studies. Our findings point to a progressive decline in diffusion rate upon increasing the time step, that is, the gap in time between two consecutive pickups, which is a signature of increasing equilibration of caffeine concentration between the lipidic mesophase and the water phase. Furthermore, the amount of released molecules at the first pickup displays negligible changes for large time steps, indicating complete equilibration in such cases. A model is introduced based on Fick’s diffusion which goes beyond the assumption of perfect-sink conditions, a common feature of the typical theoretical approaches hitherto developed. The model is shown to account quantitatively for the experimental data and is subsequently employed to clarify the interplay of the adopted release protocol with the various transport parameters in determining the final outcome of the release process. Particularly, two additional molecular drugs are considered, namely glucose and proflavine, which are, respectively, more hydrophilic and hydrophobic than caffeine, thus allowing elucidating the role of molecular partitioning.

Lipidic drug delivery systems: is the microbiome a cause for concern?

“…This coupled diffusion problem was solved numerically by considering standard discretization techniques [ 46 ]. Finally, the total fraction of hexagonal phase was computed as .…”

Coencapsulation of Gemcitabine and Thymoquinone in Citrem–Phosphatidylcholine Hexosome Nanocarriers Improves In Vitro Cellular Uptake in Breast Cancer Cells

“…Notably, drug release from liquid crystalline mesophases is modeled assuming an underlying Fickian diffusion. 67 As pH is known to alter the dynamics of the drug release of LLCNs, release studies conducted in the appropriate pH range will be needed to recapitulate the physiological environment. Modulation of a rapid (burst) release in a low pH environment may be favorable in the case of acidic tumor organelles, which could facilitate a greater anticancer effect.…”

“…In the present study, TQ release conformed to the Weibull model, while Gem release was best-fit to the Korsmeyer–Peppas model (Figure S5 and Table S1 of the Supporting Information). Notably, drug release from liquid crystalline mesophases is modeled assuming an underlying Fickian diffusion . As pH is known to alter the dynamics of the drug release of LLCNs, release studies conducted in the appropriate pH range will be needed to recapitulate the physiological environment.…”

Interplay of Hydropathy and Heterogeneous Diffusion in the Molecular Transport within Lamellar Lipid Mesophases

“…Moreover, the rich structural landscape of lipid mesophases has recently been shown to be naturally explored during digestion of tryglycerides, which likely impacts the delivery of drugs embedded in such hosts [ 16 ]. As a consequence, a large amount of research has been devoted to understanding how the chemical and structural features of lipid mesophases influence their transport properties [ 5 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. Experimental efforts in characterizing the molecular transport through lipid mesophases have unveiled an extensive palette of delivery performance depending on factors such as the geometry and symmetry of the lipid mesophase, the size of the diffusion domain, the hydropathy of the diffusing molecule, and lipid–solvent composition.…”