Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)


Pharmaceutical Sciences

Research Advisor

Atul J. Shukla, Ph.D.


Bernd Meibohm, Ph.D. Casey Laizure, Pharm. D. James R. Johnson, Ph.D. Yingxu Peng, Ph.D.


carbopol, hot melt granulation, controlled release tablet, Nearinfrared, dissolution prediction


Carbopol is crosslinked acrylic acid. Carbopol can be used in developing formulations for transdermal, oral, rectal use. It is forms strong gel in low concentration. Therefore, it can be used in low concentration in developing controlled release formulations. This increases the cost effectiveness and number of formulation options. In spite of its effectiveness, carbopol is one of the most efficient however underutilized polymer in oral controlled drug delivery system development. This is attributed to the difficulty in processing the carbopol. Carbopol has poor flow characteristics and stickiness. Objective of our research is to eliminate processing difficulties of carbopol using hot melt granulation process and to develop sustained release oral formulations of a basic (Propranolol HCl) and an acidic drug (Glipizide).

Hot melt granulation was used to prepare free-flowing, directly compressible carbopol-wax blends. Evaluation of granular characteristics of carbopol-wax blends indicated that changes in the granular characteristics is dependent on process variables such as granulation temperature, granulation time and mixing speed. At higher granulation temperature, the granulation process became sensitive to granulation time and mixing speed. Thus, for developing robust granulation process to prepare carbopol-wax blends, the granulation must be done with lower granulation temperatures.

Carbopol is an acidic polymer and forms complex with basic drugs. Carbopol-basic drug complex has poor solubility. Hence oral controlled delivery system containing carbopol and basic drug, result in incomplete drug release. Water uptake and tablet erosion studies confirmed that incomplete drug release is a result of ionic complexation and absence of tablet erosion. Thus, by selecting appropriate carbopol grade, extent of ionic complexation was reduced and by using soluble filler in the formulation, an USP compliant controlled release oral formulation of propranolol hydrochloride was developed.

Controlled release properties of carbopol matrix containing Glipizide were evaluated. Formulations containing lactose as filler, either had long lag time or burst release based on the concentration of lactose in the formulation. Formulations containing Avicel yielded tablets with high hardness and zero order drug release. The drug release pattern of Avicel based formulations was dependent on drug-polymer ratio. Release of Glipizide from Avicel based formulations was dependent on compression force. Bioequivalent formulation of Glipzide was prepared using carbopol-wax blend.

Near infrared spectrophotometer was used to predict dissolution profiles of propranolol sustained release tablets non-destructively. Three different modeling algorithms were compared for their predictability. K-nearest neighbors algorithm (KNN) yielded models with better predictability compared to partial least squares algorithm and support vector machines algorithm. Model validation was performed using independent data set. Model validation confirmed that KNN models can non-destructively predict dissolution profiles of sustained release propranolol tablets prepared at two different compression forces.