Data from wall friction testing and physical property characterization of over 100 pharmaceutical powders, blends, and granulations have been analyzed. The analyses focused on data for stainless ...steel surfaces with the most common finishes for pharmaceutical powder processing equipment, either a 2B cold rolled mill finish or an electropolished 2B surface. Active pharmaceutical ingredients exhibited the highest friction against these surfaces, whereas active granulations exhibited the least friction. The typical (median) wall friction angle for an active blend on 2B stainless steel was 22° versus 18° for an active granulation. Typical wall friction values on electropolished 2B surfaces were about 17° and 12° for active blends and granulations, respectively. Blends typically exhibited larger wall friction angles than the granulations suggesting that simple blends will usually require hoppers or bins with steeper walls to achieve mass flow. Lower wall friction angles were consistently observed against the smoother electropolished 2B surface, and, thus, the wall surface finish should be considered when designing bins and hoppers for use with pharmaceutical powders. The wall friction angles of blends and granulations did not show any definite trend as the percentage of active pharmaceutical ingredient increased.
Predicting the crystallization propensity of drug-like molecules is one of the most significant challenges facing pharmaceutical scientists today. Despite the importance of being able to understand ...what structural features of a molecule (polarity, molecular size, etc.) and which experimental conditions (temperature, concentration, etc.) permit a molecule to crystallize, there has been very little published work focused on this topic. This commentary provides a short overview of recent progress in this area and points to potential experimental and computational approaches that might be used in the future.
Excipient Taxonomy for the 21st Century Hancock, Bruno C; Goldfarb, David J
Journal of pharmaceutical sciences,
03/2023, Volume:
112, Issue:
3
Journal Article
Peer reviewed
The performance of pharmaceutical dosage forms relies heavily on the characteristics of the excipients that are incorporated into the drug product during the manufacturing process. Therefore, it is ...imperative that formulators are able to accurately and completely specify the key chemical and physical properties of those excipients. Current approaches to describing excipients are outdated and inadequate for the needs of the 21
century and in this article we highlight the benefits of a more systematic and comprehensive approach to specifying and controlling excipient properties. We hope that this will prompt the users, suppliers, and manufacturers of excipients to take a careful look at current approaches and develop tangible proposals for attaining an enhanced future state.
Accurate and rapid crystal structure predictions have the potential to transform the development of new materials, particularly in fields with highly complex molecular structures (such as in drug ...development). In this work we present a novel cloud-computing crystal structure prediction (CSP) platform with the capability of scheduling hundreds of thousands CPU cores and integrating cutting-edge computational chemistry algorithms. This new cloud-computing based CSP platform has been applied to three crystalline drug substances of increasing complexity. The lattice energies of the experimental crystal structures are all within 4.0 kJ/mol of the lowest energy predicted structures. On the basis of the results of this work, the algorithm improvement and the mass computational power of cloud computing can reduce the whole CSP process to just 1–3 weeks for Z′ = 1 systems and less than 5 weeks for significantly more complex systems. Furthermore, it is possible to simultaneously perform calculations for multiple molecules if desired. As a result of these improvements, CSP calculations can potentially be applied in conjunction with state-of-the-art experimental screening techniques to reduce the risk of finding new solid forms after product launch provided that a sufficient number of stoichiometries and space groups are explored.
Accurate prediction of the discharge rate from hoppers is important in many industrial processes involving the handling of granular materials. The present work investigates the parameters affecting ...the discharge rate using the discrete element method (DEM). The effects of particle properties (particle size and size distribution) and hopper geometry (hopper width, outlet width, angle and fill height) are studied and compared to previously published experimental correlations. The results indicate that DEM simulations are fully capable of reproducing trends in the discharge rate that are well-known experimentally. For example, particle size and hopper width are shown to have a minimal influence on the discharge rate. In addition, for rectangular hoppers, the discharge rate is shown to vary with the outlet width raised to the
3
2
power as given by the modified Beverloo correlation. The DEM simulations are also used to explore a wider range of parameters that have not been or are not easily explored experimentally. For example, the effects of hopper friction, particle friction, coefficient of restitution are investigated, and particle friction is shown to have a significant influence on the hopper discharge behavior.
This article is the first of two parts in which algorithms are presented concerning the contact detection between two cylinders, and a cylinder and a flat surface. This first part presents the ...equations for contact detection, contact location, contact overlap, and normal contact direction. The second part focuses on validation of the algorithm. These articles are the first to present validated algorithms and relations for all potential cylinder-plane and cylinder-cylinder contact scenarios (ten in all).
In this work, the discrete element method (DEM) is used to assess powder flow from hoppers and the results are compared to widely-used hopper design charts. These design charts delineate mass-flow ...and funnel-flow behavior based on the hopper wall angle and a given set of material properties. The modeled system consists of hoppers with various wall angles and frictional, non-cohesive, spherical particles. The performance is assessed by measuring the particle residence times, particle velocities, and the extent of segregation during discharge. A Mass Flow Index (MFI) based on the velocity profile data is used to quantitatively characterize the nature of the flow pattern as mass-flow, funnel-flow, or some intermediate. The DEM predictions are generally in very good agreement with the Jenike design charts. The level of agreement shown here indicates that DEM cannot only reproduce the current estimates of hopper performance, but also provide additional insight into the flow–such as the internal granular structure–that may be difficult to obtain otherwise.
The discrete element method (DEM) is used to assess powder flow from hoppers and the results are compared to widely-used hopper design charts that delineate mass-flow and funnel-flow behavior. A Mass Flow Index is used to quantitatively characterize the nature of the flow pattern as mass-flow or funnel-flow. These DEM predictions are in very good agreement with the Jenike design charts.
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To evaluate the magnitude of the solubility advantage for amorphous pharmaceutical materials when compared to their crystalline counterparts.
The thermal properties of several drugs in their ...amorphous and crystalline states were determined using differential scanning calorimetry. From these properties the solubility advantage for the amorphous form was predicted as a function of temperature using a simple thermodynamic analysis. These predictions were compared to the results of experimental measurements of the aqueous solubilities of the amorphous and crystalline forms of the drugs at several temperatures.
By treating each amorphous drug as either an equilibrium supercooled liquid or a pseudo-equilibrium glass, the solubility advantage compared to the most stable crystalline form was predicted to be between 10 and 1,600 fold. The measured solubility advantage was usually considerably less than this, and for one compound studied in detail its temperature dependence was also less than predicted. It was calculated that even for partially amorphous materials the apparent solubility enhancement (theoretical or measured) is likely to influence in-vitro and in-vivo dissolution behavior.
Amorphous pharmaceuticals are markedly more soluble than their crystalline counterparts, however, their experimental solubility advantage is typically less than that predicted from simple thermodynamic considerations. This appears to be the result of difficulties in determining the solubility of amorphous materials under true equilibrium conditions. Simple thermodynamic predictions can provide a useful indication of the theoretical maximum solubility advantage for amorphous pharmaceuticals, which directly reflects the driving force for their initial dissolution.
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