Surface Characterization as a Tool for Identifying the Factors Affecting the Dissolution Rate of Amorphous Solid Dispersion Tablets.

An amorphous solid dispersion (ASD) is a commonly used approach to enhancing the dissolution of poorly aqueous soluble drugs. Selecting the desired polymer and drug loading can be time-consuming. Surface properties, such as surface composition and wetting behavior, are essential factors controlling the dissolution of ASD tablets. Thus, our study aims to use surface characterization to understand the factors that affect the dissolution rate of ASD tablets. In this work, we prepared ASDs with itraconazole and hypromellose acetate succinate (HPMCAS) using spray drying. ASDs were prepared using three grades of HPMCAS and different drug loading levels (10%, 30%, and 50%). We prepared ASD tablets with two porosities. For each tablet, contact angles were measured using the Drop Shape Analyzer; surface free energies, disperse, and polar fractions were calculated based on the contact angles. We conducted near-infrared (NIR) and dissolution measurements of ASD tablets. Principal component analysis (PCA) was carried out to investigate the NIR spectra further. The relative PCA scores were reported with other sample properties. A partial least square (PLS) model using NIR scores, tablets' wetting properties, and dissolution rates revealed that water and buffer contact angles, surface free energy, and polar fraction are the most significant factors attributing to the dissolution rate of ASD tablets. This work understood the interplay between the surface properties and the dissolution rate of ASD tablets. Moreover, surface characterization can be the tool to screen the formulation and compaction process of ASD tablets in early development.

The effect of dynamic wetting pressure on contact angle measurements.

HYPOTHESIS: The drop deposition technique can impact contact angle measurements. We hypothesized that the drop pinch-off, during the traditionally used pendant drop technique, significantly alters the static contact angle. The capillary waves and dynamic wetting pressure generated during the pendant drop deposition are the source for forced spreading, which can be circumvented by alternative liquid-needle drop deposition techniques. EXPERIMENTS: To compare the role of drop pinch-off and resultant dynamic wetting pressure, we meticulously observed and quantified the entire drop deposition process using high speed imaging until the drop attains the static contact angle in both cases, namely pendant drop and liquid needle deposition technique. Conventionally used standard substrates are compared using both techniques and further compared using literature data. The capillary waves and corresponding drop shape variations are analysed for quantifying the dynamic wetting pressure by measuring drop base diameter, contact angle and centre of mass. FINDINGS: We compared three parameters - drop pinch-off, spreading behaviour and respective static contact angles along with the resultant dynamic wetting pressure for both the techniques, i.e., pendant drop and liquid-needle. For the pendant drop technique we observed a pronounced drop volume dependency of these parameters even though the corresponding Bond numbers are less than unity. In contrast, for the liquid needle there is no such dependency. With a theoretical argument corroborating experimental observations, this work highlights the importance of a well controlled drop deposition, with a minimum wetting pressure, in order to guarantee contact angle data that is independent of drop deposition effects, thereby only reflecting the substrate properties.

Nanoscale definition of substrate materials to direct human adult stem cells towards tissue specific populations.

The development of homogenously nano-patterned chemically modified surfaces that can be used to initiate a cellular response, particularly stem cell differentiation, in a highly controlled manner without the need for exogenous biological factors has never been reported, due to that fact that precisely defined and reproducible systems have not been available that can be used to study cell/material interactions and unlock the potential of a material driven cell response. Until now material driven stem cell (furthermore any cell) responses have been variable due to the limitations in definition and reproducibility of the underlying substrate and the lack of true homogeneity of modifications that can dictate a cellular response at a sub-micron level that can effectively control initial cell interactions of all cells that contact the surface. Here we report the successful design and use of homogenously molecularly nanopatterned surfaces to control initial stem cell adhesion and hence function. The highly specified nano-patterned arrays were compared directly to silane modified bulk coated substrates that have previously been proven to initiate mesenchymal stem cell (MSC) differentiation in a heterogenous manner, the aim of this study was to prove the efficiency of these previously observed cell responses could be enhanced by the incorporation of nano-patterns. Nano-patterned surfaces were prepared by Dip Pen Nanolithography (DPN) to produce arrays of 70 nm sized dots separated by defined spacings of 140, 280 and 1000 nm with terminal functionalities of carboxyl, amino, methyl and hydroxyl and used to control cell growth. These nanopatterned surfaces exhibited unprecedented control of initial cell interactions and will change the capabilities for stem cell definition in vitro and then cell based medical therapies. In addition to highlighting the ability of the materials to control stem cell functionality on an unprecedented scale this research also introduces the successful scale-up of DPN and the novel chemistries and systems to facilitate the production of homogeneously patterned substrates (5 mm2) that are applicable for use in in vitro cell conditions over prolonged periods for complete control of material driven cell responses.

Electrically biased nanolithography with KOH-coated AFM tips.

This letter provides the first study aimed at characterizing the desorption and nanolithographic processes for SAM-coated, gold-coated silicon substrates oxidatively patterned with an AFM with a tip under potential control. The process either results in recessed patterns where the monolayer has been removed or raised structures where the monolayer has been removed and silicon oxidation has taken place. Eleven different SAMs have been studied, and the type of pattern formed depends markedly upon SAM chain length, end functional group, and applied bias. We show how local pH and choice of monolayer can be used to very effectively control the type of pattern that is ultimately formed. Interestingly, we show that hydroxide anion accessibility to the substrate surface is one of the most significant factors in determining the pattern topography. Moreover, control over the pattern topography can be achieved by controlling the concentration of the KOH in the water meniscus formed at the point of contact between tip and surface in the context of a bias-controlled DPN experiment with a KOH-coated tip. The work provides important insight into the factors that control SAM desorption and also ways of controlling the topography of features made in a potential-controlled scanning probe nanolithographic process.