Apparent dissolution rate enhancement of poorly-water soluble drugs by adsorption technique

<p>Nearly 70% of the new chemical entities (NCE’s) discovered are poorly-water soluble drugs and the number of poorly-water soluble drugs are increasing rapidly in the drug discovery. Most of the NCE’s are lipophilic and have dissolution rate issues. Low dissolution rate of the drugs result in poor bioavailability. To overcome poor bioavailability, an adsorption technique is developed to enhance the apparent dissolution rate of poorly-water soluble drugs. In this study, two poor-water soluble model drugs, ibuprofen and carvedilol were used. Methanol, DMF, DMSO and PEG400 were used as solvents and microcrystalline cellulose was used as an adsorbent. Pure model drugs, physical mixtures and prepared composites were characterized by using FTIR, DSC, XRD and dissolution testing. Results showed that the composites prepared with solvents DMF, DMSO and PEG400 showed enhancement in dissolution rates of two model drugs. Characterization of the composites prepared by using non-volatile solvents showed successful conversion of crystalline model drugs into solution state. Whereas, composites prepared by using volatile solvent showed similar results like physical mixtures and pure drug. Ibuprofen composites containing DMF, DMSO and PEG400 showed 9.4, 7.4 and 1.8 folds of increase in apparent dissolution rate, respectively. Whereas carvedilol composites containing DMF and DMSO showed 11.52 and 3.4 folds of increase in apparent dissolution rate. Four months of stability study were conducted on prepared composites at both 40°C and room temperature. It was observed that prepared composites were stable after 4 months and exhibited similar dissolution rate. In conclusion, the use of non-volatile solvents disrupted the crystal structure but also retained the drug in solution state which in turn enhanced the apparent dissolution rate of model drugs used. From the observed results we conclude that this method has a potential to replace existing techniques to enhance the apparent dissolution rate of the drug and stability of the composites.</p>

Name thesis:degree_name

Master of Science (M.S.)

Level thesis:degree_level

Thesis - Pacific Access Restricted

Discipline thesis:degree_discipline

Pharmaceutical and Chemical Sciences

Year dc:date.available

2015

Author dc:creator

• Vutukuru, Naresh Kumar Reddy

Contributors dc:contributor

• Xiaoling Li

• Pharmacy sciences
• Health and environmental sciences
• Chemicals and Drugs
• Chemistry
• Medical Pharmacology
• Medicinal-Pharmaceutical Chemistry
• Medicine and Health Sciences
• Pharmaceutical Preparations
• Pharmacy and Pharmaceutical Sciences
• Physical Sciences and Mathematics

Licence

• http://rightsstatements.org/vocab/InC/1.0/

Identifier

9781339847115

OAI identifier oai:identifier

oai:scholarlycommons.pacific.edu:uop_etds-1268