Solution Coating of Pharmaceutical Nanothin Films and Multilayer Nanocomposites with Controlled Morphology and Polymorphism

Abstract

Nanosizing is rapidly emerging as an alternative approach to enhance solubility and thus the bioavailability of poorly aqueous soluble active pharmaceutical ingredients (APIs). Although numerous techniques have been developed to perform nanosizing of API crystals, precise control and modulation of their size in an energy and material efficient manner remains challenging. In this study, we present meniscus-guided solution coating as a new technique to produce pharmaceutical thin films of nanoscale thickness with controlled morphology. We demonstrate control of aspirin film thickness over more than 2 orders of magnitude, from 30 nm to 1.5 μm. By varying simple process parameters such as the coating speed and the solution concentration, the aspirin film morphology can also be modulated by accessing different coating regimes, namely the evaporation regime and the Landau-Levich regime. Using ellipticine-a poorly water-soluble anticancer drug-as another model compound, we discovered a new polymorph kinetically trapped during solution coating. Furthermore, the polymorphic outcome can be controlled by varying coating conditions. We further performed layer-by-layer coating of multilayer nanocomposites, with alternating thin films of ellipticine and a biocompatible polymer, which demonstrate the potential of additive manufacturing of multidrug-personalized dosage forms using this approach.

Understanding the Meniscus‐Guided Coating Parameters in Organic Field‐Effect‐Transistor Fabrications

“…Since the solubility limit of the C 8 ‐BTBT would vary in different solvents, a relatively low concentration of 1 mg mL −1 was adopted for all the experiments to ensure all the cases are below the solubility limit . For the shearing speed, v , a moderate speed for the MGC technique, 100 µm s −1 , was used . The polarized optical microscope (POM) images of the deposited C 8 ‐BTBT thin films under different T and T b are compared in Figure .…”

Repurposing DNA-binding agents as H-bonded organic semiconductors

“…9). Using this method, the kinetic stability of metastable forms can be substantially enhanced by the combined mechanism of nanoconfinement and kinetic trapping as demonstrated in our previous works 30,34–37 . The alignment, crystallinity, and polymorph identity of the solution coated ellipticine thin films were characterized using a combination of cross-polarized optical microscopy (CPOM), atomic force microscopy (AFM) and grazing incidence X-ray diffraction (GIXD) (Fig.…”

“…In this section, we discuss the role of π–π stacking and H-bonding in guiding the assembly of ellipticine and the emergent charge transport properties predicted from quantum-chemical simulations on the basis of experimental crystal structures (see Methods). Using various single-crystal growth and solution printing techniques 30 , we obtained two different crystal polymorphs of ellipticine. Their single-crystal structures are shown in Fig.…”

Non‐Contact Mass Density and Thermal Conductivity Measurements of Organic Thin Films Using Frequency–Domain Thermoreflectance

“…The controlled deposition of organic molecules is an emerging area of interest in the development of thin films for drug delivery, [1][2][3] explosive materials at sub-millimeter length scales, [4][5][6][7] and novel coatings for thermal barriers. [8] Although thin film organics have reaped the dimensional benefits of semiconductor processes such as physical vapor deposition (PVD), their synthesis often results in microstructures that vary both spatially and across the film thickness.…”

“…[17,18] The thermal conductivity on the other hand, can provide key insights into the amorphous stability of pharmaceutical ingredients that ultimately determines their bioavailability. [3,19,20] For thin-film thermal barriers, both the mass density and thermal conductivity play important roles since they are often passive and subjected to transient thermal loads. [8] Considering that the condition of engineered surfaces, [12] microscopic defects, [21] novel…”