Development of a HPMC-based controlled release formulation with hot melt extrusion (HME).

The objective of this study was to develop hydroxypropyl methylcellulose (HPMC) based controlled release (CR) formulations via hot melt extrusion (HME) with a highly soluble crystalline active pharmaceutical ingredient (API) embedded In the polymer phase. HPMC is considered a challenging CR polymer for extrusion due to its high glass transition temperature (Tg), low degradation temperature, and high viscosity. These problems were partially overcome by plasticizing the HPMC with up to 40% propylene glycol (PG). Theophylline was selected as the model API. By using differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), dynamic mechanical analysis (DMA), and X-ray powder diffraction (XRPD), the physical properties of the formulations were systematically characterized. Five grades of HPMC (Methocel(®)) - E6, K100LV, K4M, K15M, and K100M - were tested. The extrusion trials were conducted on a 16 mm twIn screw extruder with HPMC/PG placebo and formulations containing theophylline/HPMC/PG (30:42:28, w/w/w). The dissolution results showed sustained release profiles without burst release for the HPMC K4M, K15M, and K100M formulations. The extrudates have good dissolution stability after being stressed for 2 weeks under 40°C/75% RH open dish conditions and the crystalline API form did not change upon storage. Overall, the processing windows were established for the HPMC based HME-CR formulations.

Reply to "Comment on 'Microscopic kinetic theory of the mean collision force of a particle moving in rarefied gases' ".

The relative speed distribution function [Eq. (2)] in the Comment is discussed. It shows that Eq. (2) in the Comment is not the distribution function that should be explored in our work and is therefore not applicable to our research.

Microscopic kinetic theory of the mean collision force of a particle moving in rarefied gases.

The friction of an incident particle interacting with the background molecules is a cornerstone in the nonequilibrium dynamics and statistics. It is reported that the Stokes force may fail while the Brown particle's size is small enough. In this work, the mean collision force of a small classical particle moving through the rarefied gases is analyzed by the direct calculation of the mean decrease of particle's velocity by elastic collisions. As an example, a whole velocity space applicable mean collision force in Maxwell gas is obtained. A self-consistent solution is further provided based on the numerical simulations. Within the low speed limit, comparison of the friction and the Stokes force has been demonstrated. Although the two forces are both proportional to the speed of the particle, their coefficients are different. Unlike the linear speed dependence of Stokes force, the linear behavior in rarefied gases is broken with increasing the speed of incident particle, and a quadratic speed dependence is resulted in high speed. This work clarifies the nonequilibrium dynamics of microscopic particles moving in rarefied gases, and can improve our microscopic understanding of the collision force.

Twisted magnon beams carrying orbital angular momentum.

Low-energy eigenmode excitations of ferromagnets are spin waves or magnons that can be triggered and guided in magnonic circuits without Ohmic losses and hence are attractive for communicating and processing information. Here we present new types of spin waves that carry a definite and electrically controllable orbital angular momentum (OAM) constituting twisted magnon beams. We show how twisted beams emerge in magnonic waveguides and how to topologically quantify and steer them. A key finding is that the topological charge associated with OAM of a particular beam is tunable externally and protected against magnetic damping. Coupling to an applied electric field via the Aharanov-Casher effect allows for varying the topological charge. This renders possible OAM-based robust, low-energy consuming multiplex magnonic computing, analogously to using photonic OAM in optical communications, and high OAM-based entanglement studies, but here at shorter wavelengths, lower energy consumption, and ready integration in magnonic circuits.

Identification and quantitation of extractables from cellulose acetate butyrate (CAB) and estimation of their in vivo exposure levels.

The purpose of this study was to qualitatively and quantitatively determine potential cellulose acetate butyrate (CAB) extractables in a way to meaningfully predict the in vivo exposure resulting from clinical administration. Extractions of CAB-381-20 were performed in several solvent systems, consistently resulting in the detection of three extractables. The extractables have been identified as acetic acid, butyric acid, and E-2-ethyl-2-hexenoic acid (E-EHA) by LC/UV, LC/MS and NMR. Extraction studies of CAB powders in acetonitrile/phosphate buffer demonstrated quantitative extraction in 1 h for acetic acid (approximately 150 microg/g), butyric acid (approximately 200 microg/g), and EHA (approximately 20 microg/g). Subsequently, extraction studies for CAB powders and coated tablets in USP simulated gastric and intestinal fluids were performed to evaluate potential in vivo exposure. Similarly, acetic and butyric acids were quantitatively extracted from CAB-381-20 powder after 24 h exposure in both USP simulated fluids. The amounts of EHA extracted from CAB powder after 24 h were determined to be 2 and 16 microg/g in USP simulated gastric and intestinal fluids, respectively. After 24 h exposure in USP simulated fluids, the maximum amount of EHA extracted corresponds to < 0.3 microg of EHA per tablet. Pepsin and pancreatin in USP simulated fluids had no effect on EHA extraction and quantitation.

The interplay of membrane formation and drug release in solution-cast films of polylactide polymers.

The interplay of phase inversion and drug release has been studied for films of several biodegradable polylactide polymers cast from solutions containing polymer, solvent, and drug (naproxen). Variables studied included polymer type and concentration, solvent type, and film casting conditions (i.e. free or forced convection, humidity). Film morphologies and thermal properties indicate that reduction of the T(g) of the amorphous poly (lactide-co-glycolide) (PLGA) and poly (d, l-lactide) (PDLLA) systems caused by the drug, inhibits stabilization of a porous, structure, regardless of dry casting conditions and drug loads. Porous membranes could be formed by wet casting; however, drug loss during casting, makes this a non-viable process. For semi-crystalline PLLA, membrane morphologies could be varied by controlling the mass transfer path to form a single-phase dense film by polymer crystallization or a liquid-liquid two-phase structure followed by locking-in by polymer crystallization. However, the lack of drug solubility in the crystalline phase leads to unfavorable drug distributions most often leading to a burst release. Release profiles for all three polymers were found to follow a two-stage release model, with a first stage diffusive release followed by zero-order release in the second stage due to polymer erosion.