A series of 2D functional covalent–organic framework (COF) membranes are computationally designed from an experimentally synthesized COF (TpPa-1) for water desalination. The COFs consist of 1,3,5-triformylphloroglucinol (Tp) and p-phenylenediamine (Pa) (TpPa-X) with various functional groups, namely TpPa-AM2, -AMC2NH2, -OC3OH, -OC4H9, -AMCOOH, -OBn and -AM3. From molecular dynamics simulations, water flux through the TpPa-X membranes is found to increase with increasing aperture size; however, it is also significantly affected by membrane functionality. In the presence of hydrophilic functional groups, TpPa-AMC2NH2, -OC3OH and -AMCOOH exhibit higher water flux than their hydrophobic counterparts of similar aperture size. This is attributed to the preferential interaction between water and hydrophilic groups, thus resulting in a larger water density at the aperture of the hydrophilic membranes. The TpPa-X membranes show exceptionally high water permeance ranging from 1216 to 3375 kg m⁻² h⁻¹ bar⁻¹, approximately three orders of magnitude higher than commercial reverse osmosis membranes. Except TpPa-AMCOOH, the membranes have salt rejection over 98%. This computational study provides quantitative understanding of the key factors governing water permeance and suggests that TpPa-X membranes might be interesting for water desalination.

One of the most realistic approaches for delivering actives (pharmaceuticals/cosmetics) deep into skin layers is encapsulation into nanoparticles (NPs). Nonetheless, molecular-level mechanisms related to active delivery from NPs to the skin have scarcely been studied despite the large number of synthesis and characterization studies. We herein report the underlying mechanism of active translocation and permeation through the outermost layer of skin, the stratum corneum (SC), via molecular dynamics (MD) simulations complemented by experimental studies. A SC molecular model is constructed using current state-of-the-art methodology via incorporating the three most abundant skin lipids: ceramides, free fatty acids, and cholesterol. As a potent antioxidant, ferulic acid (FA) is used as the model active, and it is loaded into Gelucire 50/13 NP. MD simulations elucidate that, first, FA-loaded NP approaches the skin surface quickly, followed by slight penetration and adsorption onto the upper skin surface; FA then translocates from the NP surface to the skin surface due to stronger NP–skin interactions compared to the FA–NP interactions; then, once FA is released onto the skin surface, it slowly permeates deep into the skin bilayer. Both the free energy and resistance to permeation not only indicate the spontaneous transfer of FA from the bulk to the skin surface, but they also reveal that the main barrier against permeation exists in the middle of the lipid hydrophobic tails. Significantly lower diffusion of FA is obtained in the main barrier region compared to the bulk. The estimated permeability coefficient (log P) values are found to be higher than the experimental values. Importantly, the permeation process evaluated via MD simulations perfectly matches with experiments. The study suggests a molecular simulation platform that provides various crucial insights relating to active delivery from loaded NP to skin, and it could facilitate the design and development of novel NP-based formulations for transdermal delivery and the topical application of drugs/cosmetics.

Solid dispersion of poorly soluble APIs is known to be a promising strategy to improve dissolution and oral bioavailability. To facilitate the development and commercialization of a successful solid dispersion formulation, understanding of intermolecular interactions between APIs and polymeric carriers is essential. In this work, first, we assessed the molecular interactions between various delayed-release APIs and polymeric excipients using molecular dynamics (MD) simulations, and then we formulated API solid dispersions using a hot melt extrusion (HME) technique. To assess the potential API–polymer pairs, three quantities were evaluated: (a) interaction energy between API and polymer [electrostatic (E_coul), Lenard-Jones (E_LJ), and total (E_total)], (b) energy ratio (API–polymer/API–API), and (c) hydrogen bonding between API and polymer. The E_total quantities corresponding to the best pairs: NPX-Eudragit L100, NaDLO–HPMC(P), DMF–HPMC(AS) and OPZ–HPMC(AS) were −143.38, −348.04, −110.42, and −269.43 kJ/mol, respectively. Using a HME experimental technique, few API–polymer pairs were successfully extruded. These extruded solid forms did not release APIs in a simulated gastric fluid (SGF) pH 1.2 environment but released them in a simulated intestinal fluid (SIF) pH 6.8 environment. The study demonstrates the compatibility between APIs and excipients, and finally suggests a potential polymeric excipient for each delayed-release API, which could facilitate the development of the solid dispersion of poorly soluble APIs for dissolution and bioavailability enhancement.

Two novel polymorphs of a cocrystal involving phloretin and nicotinamide were identified and found where the polymorphs show distinct crystal structures, photoluminescence, and dissolution rates.