Biomedical subjects

Fernando J Muzzio

Publications and source records attributed to Fernando J Muzzio.

8 recordsLinked to original sources

PubMed2006

An experimental/computational approach for examining unconfined cohesive powder flow.

This paper describes a new method to quantitatively measure the flow characteristics of unconfined cohesive powders in a rotating drum. Cohesion plays an important role, affecting flow properties/characteristics, mixing rates, and segregation tendencies. The method relies on measuring the change in center of mass of the powder bed as it avalanches in the vessel, using a load cell that is sampled continuously. Filtering and analysis of the signal is done using Fast-Fourier transform into the frequency domain, where noise is eliminated using signal processing methods. The filtered data is transformed back to the time domain by using an inverse Fast-Fourier transform to give quantitative information on the powder flow characteristics. In order to understand the nature of the forces controlling powder flow behavior, a computational model was developed to estimate the relationship between inter-particle cohesive strength and experimental measurements. A "flow index" generated by the method correlates well with the degree of bed expansion (dynamic dilation) of the cohesive powders. The flow index also predicts the dynamics of flow through hoppers. As the flow index increases it becomes increasingly difficult for the powder to flow through the hoppers.

Gravitation↗

PubMed2006

Characterizing powder mixing processes utilizing compartment models.

Powder mixing has been the subject of substantial research due to its importance in a variety of industrial sectors, including pharmaceuticals, food, and polymer manufacturing. Although a number of different models have been proposed in the literature, most of them are either empirical or require computationally intensive calculations that make them difficult to implement for realistic systems. The aim of this paper is to develop a simplified framework, based on compartment modeling that efficiently and accurately captures the system behavior. Using the V-blender as a model system, the compartment modeling approach was used to illustrate the effects of vessel loading on mixing as well as the impact of sampling methods on the accuracy of mixing characterization.

Chemistry, Pharmaceutical↗

PubMed2006

Shear-induced variability in the United States Pharmacopeia Apparatus 2: modifications to the existing system.

The hydrodynamics within the United States Pharmacopeia Apparatus 2 have been shown to be highly non-uniform with a potential to yield substantial variability in dissolution rate measurements. Through the use of readily available engineering tools, several geometric modifications to the device were evaluated in this study. Specifically, we examined the influence of impeller clearance, agitator type (radial and axial), and vessel geometry (PEAK vessel) on the fluid flow properties and their relation to measured dissolution rates. Increasing the impeller clearance was observed to exacerbate the heterogeneity in shear and would likely result in greater variability in dissolution measurements. Altering the impeller type was shown to yield changes in the hydrodynamic behavior; however, the overall properties and problems with the test remain the same. Use of the PEAK vessel was observed to reduce shear heterogeneity in the regions where tablets are most likely to visit during testing; however, higher shear rates may result in the inability to discriminate between true differences in dissolution rates.

Chemistry, Pharmaceutical↗

PubMed2005

Hydrodynamics-induced variability in the USP apparatus II dissolution test.

The USP tablet dissolution test is an analytical tool used for the verification of drug release processes and formulation selection within the pharmaceutical industry. Given the strong impact of this test, it is surprising that operating conditions and testing devices have been selected empirically. In fact, the flow phenomena in the USP test have received little attention in the past. An examination of the hydrodynamics in the USP apparatus II shows that the device is highly vulnerable to mixing problems that can affect testing performance and consistency. Experimental and computational techniques reveal that the flow field within the device is not uniform, and dissolution results can vary dramatically with the position of the tablet within the vessel. Specifically, computations predict sharp variations in the shear along the bottom of the vessel where the tablet is most likely to settle. Experiments in which the tablet location was carefully controlled reveal that the variation of shear within the testing device can affect the measured dissolution rate.

Chemistry, Pharmaceutical↗

PubMed2005

Mixing of non-Newtonian fluids in steadily forced systems.

We investigate mixing in a viscoelastic and shear-thinning fluid-a very common combination in polymers and suspensions. We find that competition between elastic and viscous forces generates self-similar mixing, lobe transport, and other characteristics of chaos. The mechanism by which chaos is produced is evaluated both in experiments and in a simple model. We find that chaotic flow is generated by spontaneous oscillations, the magnitude and frequency of which govern the extent of chaos and mixing.

Body Fluids↗

PubMed2004

V-blender segregation patterns for free-flowing materials: effects of blender capacity and fill level.

Stable segregation patterns are shown to form in V-blenders over a wide range of vessel capacities, fill levels, and rotation rates. Slight changes in either rotation rate or fill level induce changes in pattern formation. Trajectory segregation in two regions of the flow, accumulating over many flow periods, drives segregation pattern formation. Scaling criteria derived to relate particle velocities to vessel size and rotation rate in rotating cylinders successfully predict the rotation rate for the transition between patterns across V-blenders of 0.8-26.5 quart total capacity. This agreement suggests that pattern formation is governed by the magnitude of particle velocities. Regardless of vessel size, when particle velocities at specific regions of the blender are below a certain value, one particular pattern appears, and when they increase beyond that speed (i.e. by changing the rotation rate or the vessel size), a different pattern emerges. A scaling relation between segregation pattern formation and blender fill level was not identified because the complex flow patterns in the V-blender (the length of the flowing layer and the mixture center of mass relative to the blender are constantly oscillating) preclude the determination of a relationship between blender fill level and particle velocities.

Chemical Phenomena↗

PubMed2003

Engineering tools for understanding the hydrodynamics of dissolution tests.

In this article, three well-established engineering tools are used to examine hydrodynamics in dissolution testing apparatuses. The application of these tools would provide detailed information about the flow, shear, and homogeneity in dissolution tests. Particle image velocimetry successfully measures two-dimensional cross-sections of the velocity field in an experimental device under both laminar and turbulent conditions. The velocity field is also calculated with computational fluid dynamics (CFD), which can rapidly provide data that is difficult or impossible to obtain experimentally. The occurrence of segregated regions within a USP Apparatus II under mild agitation conditions is revealed by CFD simulations and confirmed by laser-induced fluorescence experiments. The results clearly demonstrate that under current operation settings, the USP Apparatus II operates in a regime where the flow is in incipient turbulence, which is a highly time-dependent condition that might explain possible inconsistencies in dissolution results. It is further demonstrated that proposed changes advocating lower speeds or smaller vessels displace the system toward laminar flow conditions characterized by segregation, compromising the robustness of the test and making it vulnerable to variability with respect to sample location.

Fluorescence↗

PubMed2002

Mixing of cohesive pharmaceutical formulations in tote (bin) blenders.

Experiments were conducted to determine the influence of process parameters such as fill level, mixing time, shear, and baffle presence along with material attributes such as initial active aggregate size and concentration on the homogeneity of a cohesive placebo formulation in a pilot plant scale tote blender. The formulation was a ternary system made up of microcrystalline cellulose, NaCl or KCl salt, and magnesium stearate. Blend homogeneity was evaluated by sampling the blend using core samplers. Salt concentration was quantified using a conductivity technique. After a brief transient mixture, homogeneity became insensitive to mixing time and initial active concentration, however, it was a strong function of fill capacity and initial active aggregate size. Sixty percent fill was found to be optimum. Active aggregate size had an adverse effect on mixture homogeneity. The best results were obtained when the salt aggregates were initially comparable in size to that of the excipient and a high shear pre-blending step was implemented prior to dilution in the tote blender. For the strongly agglomerating material examined here, pre-blending was only beneficial if the initial aggregate size was relatively small. For cohesive systems that form large and rigid aggregates, it is recommended to mill or screen the potentially agglomerating component and then mix the system in a blender equipped with an intensifier bar.

Cellulose↗