Novel Carbopol – Wax Blends for Controlled Release Oral Dosage Forms

ii ACKNOWLEDGEMENTS I would like to thank my major professor, Dr. Atul J. Shukla for his valuable support and guidance. I would also like to thank my committee members, Dr. for their valuable suggestions and guidance. I would also like to thank my present lab colleagues Dr. for their guidance and help. I thank my parents, wife and sister for supporting me at all times. My success has always been a fruit of their persistent support and help. I would like to thank Ms. Shirley Hancock for her kind helps and patience during format review of this dissertation. Health Science Center for giving me the opportunity to pursue my research. iii ABSTRACT 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 iv 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 …