Impact of Substrate Properties on the Formation of Spherulitic Films: A Case Study of Salbutamol Sulfate

Abstract

Spherulitic assemblies have applications as carriers for drug delivery and as targeting vectors. Presently, the driving force behind the formation of spherulites comprising small drug molecules is not fully understood. Herein, the impact of different substrate types on spherulitic crystallization of salbutamol sulfate (SS) was investigated. Freshly cleaved mica, silicon (111) wafer (SiW), uncoated borosilicate glass (UG), silane coated glass (CG) and stainless steel (MS) were used as substrates. It was demonstrated that the spherulite growth can be controlled via the substrate selection. Spherulite formation was inhibited on hydrophilic substrates, such as mica, possibly due to stronger intermolecular interactions between SS and the substrate than SS-SS interactions. Contact angle measurements established that mica possessed the lowest contact angle (15.1±0.5°) and the values of this parameter increased in the order of UC˂SiW˂CG˂MS. Substrate roughness also played a key role in controlling spherulite formation. SiW, UC and CG had isotropic surfaces with low average roughness, facilitating spherulite formation. Overall, this work demonstrates that it is possible to successfully produce SS spherulites using a single step process at room temperature. Furthermore, the formation of SS spherulites can be tuned by the hydrophobicity of the substrate, an approach that could be applied to assembling spherulites of other small organic molecules. Presently, the driving force behind the formation of spherulites comprising small drug molecules is not fully understood. Herein, the impact of different substrate types on spherulitic crystallization of salbutamol sulfate (SS) was investigated. Freshly cleaved mica, silicon (111) wafer (SiW), uncoated borosilicate glass (UG), silane coated glass (CG) and stainless steel (MS) were used as substrates. It was demonstrated that the spherulite growth can be controlled via the substrate selection. Spherulite formation was inhibited on hydrophilic substrates, such as mica, possibly due to stronger intermolecular interactions between SS and the substrate than SS-SS interactions. Contact angle measurements established that mica possessed the lowest contact angle (15.1±0.5°) and the values of this parameter increased in the order of UC˂SiW˂CG˂MS. Substrate roughness also played a key role in controlling spherulite formation. SiW, UC and CG had isotropic surfaces with low average roughness, facilitating spherulite formation. Overall, this work demonstrates that it is possible to successfully produce SS spherulites using a single step process at room temperature. Furthermore, the formation of SS spherulites can be tuned by the hydrophobicity of the substrate, an approach that could be applied to assembling spherulites of other small organic molecules.

Intermolecular Interactions in Functional Crystalline Materials: From Data to Knowledge

“…First, analysis of crystal faces of the desired solid form was carried out to reveal functional groups on one of the main faces; then, the monolayer containing functional groups are able to form stable synthons with the above functional groups, which was used during crystallization ( Figure 6b). Not only predesigned monolayers but also polymers [170,171] and additives ( Figure 6c) Having access to CSD-Materials, one can predict the morphology using the Bravais, Friedel, Donnay, and Harker (BFDH) crystal morphology tool ( Figure 5). This method implies the idea that the crystals are preferable to grow along the direction with strong intermolecular interactions.…”

“…First, analysis of crystal faces of the desired solid form was carried out to reveal functional groups on one of the main faces; then, the monolayer containing functional groups are able to form stable synthons with the above functional groups, which was used during crystallization ( Figure 6b). Not only predesigned monolayers but also polymers [170,171] and additives ( Figure 6c) [172,173] can be used as templates for crystallization. For example, β-1,4-saccharides act as templates to produce the metastable form III of paracetamol at crystallization from melt readily forming H-bonds with the (010) surface of form III [172], while the presence of sulfamides in solution promotes crystallization of γ-pyrazinamide from aqueous solutions [173].…”

“…At the same time, the test carbonyl oxygen and uncharged NH groups can be successfully applied to reveal positions of acceptors and donor of C-H...O [170,[255][256][257] and C-H...N [258] bonding. It was demonstrated in Refs.…”

“…The itraconazole lacks any donors of strong H-donors but has a number of competing acceptors of H- This tool has been applied mainly for the analysis of strong hydrogen bonds [54,170,190,194,[248][249][250][251] in accord with the first test functional groups suggested within this tool, and the first paper published to describe it. Mutual disposition of hot spots can be used to find functional groups of the same molecule [245], co-formers [243,249,250], active sites in a binding pocket of a macromolecule [252], or surface inhibitors [170], which match a given pattern of interaction preferences. Analysis of polymorphs of some drugs demonstrated that disposition of H-bond donors and acceptors close to the hotspots are indicative for the more stable polymorph even if a molecule realizes less likely conformation [190].…”

Optimising the in vitro and in vivo performance of oral cocrystal formulations via spray coating

“…The surface morphology of the beads, previously coated with gold/palladium, was evaluated using scanning electron microscopy (SEM). In addition, the morphology of the 1000 µm coated and uncoated non-pareil sugar beads was imaged by using a 9MP 2-200 x digital microscope (Conrad Electronics, Germany) and images were processed by Image J v1.46 image analysis software [19]. Beads were cut in half in order to see in more detail the thickness of the coating layer.…”