Assessment of co-processing of cellulose II and silicon dioxide as a platform to enhance excipient functionality

Abstract

This thesis project studied microcrystalline cellulose II (CII), a polymorphic form of cellulose, which has lower mechanical properties, less plastic deformation, higher elastic recovery and faster disintegration properties than microcrystalline cellulose I (CI). Also, the effects of processing and silicification on CII materials were investigated. Particle modification through spray drying, wet granulation and spheronization was employed to improve CII performance. Spray-drying (SDCII) and wet granulation (WGCII) produced materials with no difference in mechanical or disintegration properties from unprocessed CII, but did show an increase in density and particle flow. Conversely, spheronization (SPCII) showed the poorest mechanical properties compared to CII. Further, SDCII showed better dilution potential than CII. Thus the advantages of SDCII were apparent when it was mixed with a poorly compressible drug (acetaminophen) because fibrous CII was converted to spheroidal particles through spray drying. The rapid disintegration of SDCII and CII compacts was due to water wicking through capillaries followed by compact bursting. Compacts of ibuprofen mixed with SDCII and Avicel ® PH-102 had comparable disintegration rates and release profiles compared to ibuprofen formulated with commercial disintegrants and Avicel ® PH-102, especially at levels 10% w/w. Adding fumed silica into CII particles through spray drying, wet granulation (WGCII) and spheronization (SPCII) at 2-20% w/w was also studied. Silicification increased physical properties such as true density, Hausner ratio, porosity, ejection force and specific surface area of SDCII and WGCII. Other properties such as bulk and tap densities were reduced due to the amorphous and light character of fumed silica. Spheronized CII showed no change in these properties with silicification. Silicification diminished lubricant sensitivity with magnesium stearate due to the competition of SiO 2 with magnesium stearate to coat CII particles. Silicification also decreased the affinity of CII for water only at the 20% w/w level due to the few silanol groups available for water interaction compared to surface hydroxyl groups on CII alone. Particle size modification of CII was process-dependent v transformed my vision of the role of pharmaceutics and physical pharmacy for drug development. I also appreciate their financial support and the initial support provided by University of Antioquia, especially to Professors Tobon and Bedoya. I also express my gratitude to Dr. Reist for his trust, support and teaching me the value of professionalism and personalized pedagogy in the Pharmacy Practice Laboratory.

Compression Vehicle: A Technical Review

“…Brittle materials get fragmented while plastic and elastic materials undergo deformation with applying pressure. The deformation may be elastic or plastic [35][36][37]. Though the material under compaction is not entirely elastic, plastic or brittle, it shows all types of behaviour, with only one type exhibiting a predominant response [37].…”

“…The deformation may be elastic or plastic [35][36][37]. Though the material under compaction is not entirely elastic, plastic or brittle, it shows all types of behaviour, with only one type exhibiting a predominant response [37]. On application of compression pressure, elastic material will undergo deformation and reassume its original shape after removing the stress.…”

Application of N-hexoyl chitosan derivatives with high degree of substitution in the preparation of super-disintegrating pharmaceutical matrices

“…Where, rbulk and rtrue are the bulk density and true density, respectively [16]. In order to characterize the flowability of the powder of CS derivatives, Hausner's ratio (R H ) and Carr's index (CI) were calculated [61].…”

Design and characterization of the material attributes of a co-processed excipient developed for direct compression tableting

“…In the formulation of tablets, excipients play a crucial role in ensuring the smooth processing, formation and robust performance of the dosage form. They have been rightly referred to as functional components of a formulation because they influence the manufacturability, stability, bioavailability and safety of the formulation 1 . Depending on the composition of the formulation, excipients may constitute more than 50 % of the entire formulation.…”