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Towards scientific manufacturing: the effects of shear rate, strain, and composition on the properties of blends and tablets
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Towards scientific manufacturing: the effects of shear rate, strain, and composition on the properties of blends and tablets
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Effects of shear rate, strain, and composition on the properties of blends and tablets
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Llusá
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Marcos
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Marcos Llusá
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Muzzio
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Fernando
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Advisory Committee
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Fernando Muzzio
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Tomassonne
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Silvina
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Silvina Tomassonne
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Marianthi
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Marianthi Ierapetritou
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Levin
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Michael
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Advisory Committee
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Michael Levin
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Michniak
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Bozena
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Advisory Committee
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Bozena Michniak
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Rutgers University
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Graduate School - New Brunswick
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theses
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2008
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2008-05
Language
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English
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electronic
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xv, 192 pages
Abstract
This dissertation aims at understanding the effects of formulation (type of excipient, APAP grade, lubricant concentration) and processing conditions (shear rate and strain) on the following properties of pharmaceutical blends and tablets:
1. Degree of Active Pharmaceutical Ingredient (API) agglomeration and homogeneity.
2. Density, flowability, and hydrophobicity of lubricated formulations.
3. Tablet hardness.
Another aim is to develop a method to assess the API de-agglomeration in blenders, when only a small fraction of the blend is sampled.
The blend properties examined are those that impact on the quality of the product: blend density determines the amount of powder that fills the tablet dies, blend hydrophobicity determines the dissolution properties of tablets, powders, or capsules, and API agglomeration determines the probability of having out-of-specification products.
The experimental method uses a shear cell where shear rate and strain can be controlled. The different blend properties are measured using suitable analytical techniques.
For the assessment of API de-agglomeration in blenders, a numerical method is developed to design sampling protocols that detect and characterize agglomerates with a degree of statistical confidence.
The results show that:
1. The degree of API agglomeration decreases as a function of strain, and independently of shear rate. A coarser API presents a significantly smaller degree of agglomeration than a finer API. De-agglomeration proceeds at very similar rates in different excipients.
2. Blend hydrophobicity increases steadily as a function of strain and lubricant concentration. Larger shear rates increase hydrophobicity even further. Tapped density of lubricated blends increases as a function of strain until reaching a maximum value, independently of shear rate. The flowability of lubricated blends is enhanced but independently of strain and shear rate they have been exposed to.
3. The tablet crushing hardness is a function of the strain applied to lubricated blends and independent of the shear rate.
The statistical method used to detect and characterize API agglomerates in blenders yields concentration profiles that compare very well to the experimental concentration profile. This procedure validates the parameters that describe the agglomerate population (with a normal distribution of sizes) in a blend.
1. Degree of Active Pharmaceutical Ingredient (API) agglomeration and homogeneity.
2. Density, flowability, and hydrophobicity of lubricated formulations.
3. Tablet hardness.
Another aim is to develop a method to assess the API de-agglomeration in blenders, when only a small fraction of the blend is sampled.
The blend properties examined are those that impact on the quality of the product: blend density determines the amount of powder that fills the tablet dies, blend hydrophobicity determines the dissolution properties of tablets, powders, or capsules, and API agglomeration determines the probability of having out-of-specification products.
The experimental method uses a shear cell where shear rate and strain can be controlled. The different blend properties are measured using suitable analytical techniques.
For the assessment of API de-agglomeration in blenders, a numerical method is developed to design sampling protocols that detect and characterize agglomerates with a degree of statistical confidence.
The results show that:
1. The degree of API agglomeration decreases as a function of strain, and independently of shear rate. A coarser API presents a significantly smaller degree of agglomeration than a finer API. De-agglomeration proceeds at very similar rates in different excipients.
2. Blend hydrophobicity increases steadily as a function of strain and lubricant concentration. Larger shear rates increase hydrophobicity even further. Tapped density of lubricated blends increases as a function of strain until reaching a maximum value, independently of shear rate. The flowability of lubricated blends is enhanced but independently of strain and shear rate they have been exposed to.
3. The tablet crushing hardness is a function of the strain applied to lubricated blends and independent of the shear rate.
The statistical method used to detect and characterize API agglomerates in blenders yields concentration profiles that compare very well to the experimental concentration profile. This procedure validates the parameters that describe the agglomerate population (with a normal distribution of sizes) in a blend.
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references.
Subject
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Topic
Chemical and Biochemical Engineering
Subject
(ID = SUBJ2);
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Topic
Tablets (Medicine)
Subject
(ID = SUBJ3);
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Topic
Drugs--Dosage forms
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Graduate School - New Brunswick Electronic Theses and Dissertations
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doi:10.7282/T31R6QWM
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ETD doctoral
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Marcos Llusa
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Rutgers University. Graduate School - New Brunswick
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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