Document Type


Date of Degree

Fall 2011

Degree Name

PhD (Doctor of Philosophy)

Degree In


First Advisor

Flanagan, Douglas R

First Committee Member

O'Shaughnessy, Patrick

Second Committee Member

Anthony, Renée

Third Committee Member

Grassian, Vicki

Fourth Committee Member

Oleson, Jacob


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 SiO2 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 rather than silicification-dependent. Additionally, silicification decreased the apparent plasticity and elastic recovery of SDCII and WGCII when compacted. The former effect along with increased powder porosity increased surface area and compressibility of SDCII and WGCII. Compact tensile strength of silicified CII materials was in the order: spray-dried > wet granulated > spheronized. This order was due to the combined effect of particle morphology and how fumed silica was incorporated and distributed within CII particles. Silicification did not affect the rapid disintegration properties of CII. Thus, diphenhydramine HCl and griseofulvin tablets prepared with silicified CII had faster disintegration and release than those prepared with commercial silicified CI (Prosolv®). Moreover, CII beads containing diphenhydramine HCl or griseofulvin had faster release profiles compared to beads prepared with Prosolv® SMCC 50 or Avicel® PH-101. This behavior showed that rapid disintegration is an intrinsic property of CII. Compact tensile strength decreased more for unsilicified CI and CII compacts stored at 75% RH, while silicified CI and CII compacts lost less tensile strength under the same conditions. Reprocessed CI materials containing acetaminophen (1:1mixtures) lost 35-72% of their original strength compared to silicified CII materials (15-25% loss) indicating more particle interaction upon recompression.



cellulose II, co-processing, drugs, excipients, pharmaceutics, Spray drying


xx, 336 pages


Includes bibliographical references (pages 315-336).


Copyright 2011 Jhon J. Rojas