Probabilistic Assessment of Glass Forming Ability Rules for Metallic Glasses Aided by Automated Analysis of Phase Diagrams.

The use of machine learning techniques to expedite the discovery and development of new materials is an essential step towards the acceleration of a new generation of domain-specific highly functional material systems. In this paper, we use the test case of bulk metallic glasses to highlight the key issues in the field of high throughput predictions and propose a new probabilistic analysis of rules for glass forming ability using rough set theory. This approach has been applied to a broad range of binary alloy compositions in order to predict new metallic glass compositions. Our data driven approach takes into account not only a broad variety of thermodynamic, structural and kinetic based criteria, but also incorporates qualitative and descriptive attributes associated with eutectic points in phase diagrams. For the latter, we demonstrate the use of automated machine learning methods that go far beyond text recognition approaches by also being able to interpret phase diagrams. When combined with structural descriptors, this approach provides the foundations to develop a hierarchical probabilistic predication tool that can rank the feasibility of glass formation.

Correlation of solid dosage porosity and tensile strength with acoustically extracted mechanical properties.

Currently, the compressed tablet and its oral administration is the most popular drug delivery modality in medicine. The accurate porosity and tensile strength characterization of a tablet design is vital for predicting its performance such as disintegration, dissolution, and drug-release efficiency upon administration as well as ensuring its mechanical integrity. In current work, a non-destructive contact ultrasonic approach and an associated testing procedure are presented and employed to quantify and relate the acoustically extracted mechanical properties of pharmaceutical compacts to direct porosity and tensile strength measurements. Based on a comprehensive set of experimental data, it is demonstrated how strongly the acoustic wave propagation is modulated and correlated to the tablet porosity and tensile strength of a compact made using spray-dried lactose and microcrystalline cellulose with varying mixture ratios. The effect of mixing ratio on the porosity and tensile strength on the resulting compacts is quantified and, with the acoustic experimental data, mixing ratio is related to the compact ultrasonic characteristics. The ultrasonic techniques provide a rapid, non-destructive means for evaluating compacts in formulation development and manufacturing. The presented approach and data could find critical applications in continuous tablet manufacturing, its real-time quality monitoring, as well as minimizing batch-to-batch quality variations.

Enhancement of the aqueous solubility and permeability of a poorly water soluble drug ritonavir via lyophilized milk-based solid dispersions.

In the present study, a lyophilized milk-based solid dispersion (SD) of ritonavir (RTV) was developed with the goal of improving its aqueous solubility. The SD was prepared by lyophilization, and characterized for its physicochemical and functional properties. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), photomicroscopy and powder X-ray diffraction (PXRD) were used to confirm the formation and robustness of the SD formulation. The prepared SD formulations were functionally evaluated by saturation solubility, in vitro drug release and ex vivo permeation studies. The optimized SD formulation exhibited a significantly higher (30-fold) aqueous solubility (11.36 ± 0.06 µg/mL), compared to the pure RTV (0.37 ± 0.03 µg/mL). The in vitro dissolution studies revealed a significantly higher (∼10-fold) efficiency of the optimized SD formulation in releasing the RTV, compared to the pure RTV. The ex vivo permeation studies with the everted intestine method showed that prepared SD formulation significantly improved the permeation of RTV (75.6 ± 3.09, % w/w), compared to pure RTV (20.45 ± 1.68, % w/w). Thus, SD formulation utilizing lyophilized milk as a carrier appears to be a promising alternative strategy to improve the aqueous solubility of poorly water soluble drugs.

The role of phospholipid as a solubility- and permeability-enhancing excipient for the improved delivery of the bioactive phytoconstituents of Bacopa monnieri.

In an attempt to improve the solubility and permeability of Standardized Bacopa Extract (SBE), a complexation approach based on phospholipid was employed. A solvent evaporation method was used to prepare the SBE-phospholipid complex (Bacopa Naturosome, BN). The formulation and process variables were optimized using a central-composite design. The formation of BN was confirmed by photomicroscopy, Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Powder X-ray Diffraction (PXRD). The saturation solubility, the in-vitro dissolution, and the ex-vivo permeability studies were used for the functional evaluation of the prepared complex. BN exhibited a significantly higher aqueous solubility compared to the pure SBE (20-fold), or the physical mixture of SBE and the phospholipid (13-fold). Similarly, the in-vitro dissolution revealed a significantly higher efficiency of the prepared complex (BN) in releasing the SBE (>97%) in comparison to the pure SCE (~42%), or the physical mixture (~47%). The ex-vivo permeation studies showed that the prepared BN significantly improved the permeation of SBE (>90%), compared to the pure SBE (~21%), or the physical mixture (~24%). Drug-phospholipid complexation may thus be a promising strategy for solubility enhancement of bioactive phytoconstituents.