Home
Resource
A mechanistic understanding of nucleation and growth in a bicomponent wet granulation system
PDF
PDF format is widely accepted and good for printing.
Plug-in required
PDF-1(32.26 MB)
Citation & Export
View Usage Statistics
Staff View

Citation & Export
Hide

Simple citation

Muthancheri, Indu. A mechanistic understanding of nucleation and growth in a bicomponent wet granulation system. Retrieved from https://doi.org/doi:10.7282/t3-jd6r-zd86

Export

Click here for information about Citation Management Tools at Rutgers.

Statistics
Hide

Description

TitleA mechanistic understanding of nucleation and growth in a bicomponent wet granulation system
NameMuthancheri, Indu (author); Ramachandran, Rohit (chair); Shapley, Nina (member); Drazer, German (member); Oka, Sarang (member); Ramachandran, Rohit (member); Rutgers University; School of Graduate Studies
Date Created2021
Other Date2021-10 (degree)
SubjectChemical engineering, Content uniformity, Hybrid Model, Multi-component, Population Balance Model, Wet granulation
Extent1 online resource (xx, 146 pages)
DescriptionWet granulation processes of more than one solid material are quite common in various particle processing industries. The materials involved during such processes may vary based on their process application. Thus, quantifying the impact of material variability on granules is critical in the field of granulation. The overall aim of this proposal is to provide an in-depth understanding of the effect of change in percentage formulation of a bi-component (two solid materials) high shear wet granulation process on the final granule attributes. Following three specific aims collectively targets to achieve the overall aim using a combined experimental and computational approach.The first aim of this study is to decouple the effect of hydrophobicity or wettability of materials from other critical properties and to experimentally determine the impact of change in percentage composition on granule growth mechanisms. Although many drug products involve materials with wettability differentials, there is a lack of understanding of how the hydrophobic behavior of materials affects the wet granulation process and granule product quality. To study the impact of wettability/hydrophobicity on granulation, two formulations were considered (I: Ibuprofen, and Microcrystalline cellulose (MCC-101), II: Acetaminophen, and MCC-101) with a wide difference in contact angle. Wet granulation results showed that the compositional distribution of components among granules of different sizes (i.e., content uniformity) is impacted by the granule growth mechanism. Ibuprofen formulation favored viscous force dominant granule growth, and acetaminophen formulation favored capillary force dominant granule growth. Due to viscous force dominant growth, ibuprofen formulation produced granules with a uniform compositional distribution of components among granules of different sizes. Capillary force dominant granule growth of acetaminophen formulation leads to weaker granules resulting in a non-uniform distribution of components among granules of different sizes.

The second objective of this work is to study the nucleation mechanism involved during liquid binder addition and to classify the nucleation mechanism observed as a function of change in percentage composition. The third and final aim is to develop a formulation-dependent hybrid modeling framework for the wet granulation process. As part of the second aim, a random forest method is used for predicting the probability of nucleation mechanism (immersion and solid-spread) depending upon the formulation hydrophobicity. The predicted nucleation probability is used to determine the aggregation rate as well as the initial particle distribution in the population balance model. The aggregation process was modeled as Type-I: Sticking aggregation and Type-II: Deformation-driven aggregation. In Type-I, the capillary force dominant aggregation mechanism is represented by the particles sticking together without deformation. In the case of Type-II, the particle deformation causes an increase in the contact area, representing a viscous force dominant aggregation mechanism. The choice between Type-I and II aggregation is determined based on the difference in nucleation mechanism that is predicted using the random forest method. The model was optimized and validated using the granule content uniformity and size distribution data obtained from the experimental studies. The proposed framework predicted content non-uniformity behavior for formulations that favored immersion nucleation and uniform behavior for formulations that favored solid-spreading nucleation.
NotePh.D.
NoteIncludes bibliographical references
Genretheses
Persistent URLhttps://doi.org/doi:10.7282/t3-jd6r-zd86
LanguageEnglish
CollectionSchool of Graduate Studies Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
Version 8.5.5
Rutgers University Libraries - Copyright ©2024