Effect of High-Energy Milling on the Dissolution of Anti-HIV Drug Efavirenz in Different Solvents.

The anti-HIV drug efavirenz (EFV) displays low and variable bioavailability because of its poor aqueous solubility. Ball milling is a simple and cost-effective alternative to traditional micronization to improve the solubility and dissolution rate of EFV. A multibody dynamics model was employed to optimize the milling process parameters, while the motion of the balls in the mill jar was monitored in operando. This led to a better understanding of the milling dynamics for efficient comminution and enhancement of EFV dissolution. The variability of results for different EFV batches was also considered. Depending on the EFV batch, there were intrinsic differences in how the milling affected the dissolution behavior and inhibition of HIV-1 infection. High-energy grinding is more effective on EFV materials containing an amorphous fraction; it helps to remove agglomeration and enhances dissolution. Polyvinylpyrrolidone (PVP) addition improves the dissolution by forming a hydrophilic layer on the EFV surface, thereby increasing the drug wettability. Polymorphism also affects the quality, dosage, and effectiveness of the drug. The mechanical stress effect and PVP addition on the EFV polymorphic transformation were monitored by X-ray powder diffraction, while the residual of ground EFV was collected after dissolution, analyzed by scanning electron microscopy, and provided insights into the morphological changes.

The Notched Stick, an ancient vibrot example.

An intriguing simple toy, commonly known as the Notched Stick, is discussed as an example of a "vibrot", a device designed and built to yield conversion of mechanical vibrations into a rotational motion. The toy, that can be briefly described as a propeller fixed on a stick by means of a nail and free to rotate around it, is investigated from both an experimental and a numerical point of view, under various conditions and settings, to investigate the basic working principles of the device. The conversion efficiency from vibration to rotational motion turns out to be very small, or even not detectable at all, whenever the propeller is tightly connected to the stick nail and perfectly axisymmetrical with respect to the nail axis; the small effects possibly observed can be ascribed to friction forces. In contrast, the device succeeds in converting vibrations into rotations when the propeller center of mass is not aligned with the nail axis, a condition occurring when either the nail-propeller coupling is not tight or the propeller is not completely axisymmetrical relative to the nail axis. The propeller rotation may be induced by a process of parametric resonance for purely vertical oscillations of the nail, by ordinary resonance if the nail only oscillates horizontally or, finally, by a combination of both processes when nail oscillations take place in an intermediate direction. Parametric resonance explains the onset of rotations also when the weight of the propeller is negligible. In contrast with what is commonly claimed in the literature, the possible elliptical motion of the nail, due to a composition of two harmonic motions of the same frequency imposed along orthogonal directions, seems unnecessary to determine the propeller rotation.