Honors Program

Honors in Chemistry

Date of Award

5-2015

Thesis Professor(s)

Sam Harirforoosh

Thesis Professor Department

Pharmaceutical Sciences

Thesis Reader(s)

Abbas Shilabin, George Poole

Abstract

Aliskiren is a non-peptide, orally active renin inhibitor with poor absorption and low bioavailability (~2.6%). In order to improve the current drug delivery system, a commercially available, biodegradable copolymer, poly(lactide-co-glycolide) (PLGA), was employed for a nanoparticle (NP) reformulation of aliskiren. An emulsion-diffusion-evaporation technique was implemented where aliskiren and PLGA were dissolved in dichloromethane, ethyl acetate, or ethyl acetate/acetone. To an aqueous phase containing 0.25% w/v didodecyldimethylammonium bromide (DMAB) as stabilizer, the previously prepared organic phase was added drop-wise. Following sonication, NP diffusion was expedited with the addition of water, and the organic phase was evaporated to form a suspension. Centrifugation was performed at 10,000 rpm, and the supernatant was analyzed for drug entrapment efficiency via ultraviolet-visible spectroscopy as well as particle morphology with the use of a transmission electron microscope (TEM). Having the highest entrapment efficiency (82.68 ± 1.18 %), ethyl acetate was used as the organic solvent in further testing, such as examining the effects of variation in DMAB stabilizer concentration (0.10, 0.25, 0.50, or 1.00% w/v) and centrifugation speed (10,000 or 12,000 rpm). The optimum formulation was ascertained through observing certain NP characteristics, such as entrapment efficiency particle size, zeta potential, and polydispersity index (PDI). A NICOMP Particle Sizer was used to measure particle size, zeta potential, and PDI. The smallest NP size (67.27 ± 0.87 nm) was accomplished with 0.50% w/v DMAB concentration using a centrifugation speed of 12,000 rpm, while the highest zeta potential (18.73 ± 0.03 mV) was detected with the 1.00% w/v DMAB concentration and a 10,000 rpm centrifugation speed. Further, the best entrapment efficiency and PDI (82.68 ± 1.18 % and 0.15 ± 0.03, respectively) were accomplished with 0.25% w/v DMAB and centrifugation at 10,000 rpm. The most favorable formulation yielding the highest zeta potential (18.73 ± 0.03 mV) was observed when DMAB stabilizer was 1.00% w/v and centrifuged at 10,000 rpm. Particle size and entrapment efficiency for this formulation were 75.67 ± 0.89 nm and 71.62 ± 0.11 %, respectively.

Document Type

Honors Thesis - Withheld

Copyright

Copyright by the authors.

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