Date of Award
1-1-2024
Document Type
Thesis
Degree Name
M.S. in Pharmaceutical Science
First Advisor
Michael A. Repka
Second Advisor
Eman Ashour
Third Advisor
Walter G. Chambliss
Relational Format
dissertation/thesis
Abstract
Simvastatin, a potent HMG-CoA reductase inhibitor, lowers cholesterol levels. It prevents cardiovascular events like heart attacks and strokes in patients with high cholesterol and heart disease. However, its oral bioavailability is limited due to its poor aqueous solubility The current study aims to enhance the solubility of the poorly water-soluble drug simvastatin through the development of self-emulsifying drug delivery systems (SEDDS). Gelucire® 48/16 (oil), Gelucire 44/14 (surfactant), and Cremophor RH40 (co-surfactant) were assessed as potential excipients for SEDDS formulation. Initial SEDDS (Before adsorption) formulations were created based on the solubility of simvastatin in solid lipid excipients, as determined by a method developed by Gattefossé. Subsequent optimization of these formulations was conducted based on In-vitro drug release studies. Lead formulations were transformed into granules of solid SEDDS (S-SEDDS) by adsorbing drug-lipid mixture onto solid carriers using the Twin Screw Granulation (TSG) approach. Interestingly, granules extruded with temperature exhibited improved drug release in dissolution studies. The lead formulations of both SEDDS (F7) and S-SEDDS (S5, S6) were evaluated for emulsification time, globule size, and polydispersity index (PDI). Additionally, the developed formulations were assessed for their solid-state properties using differential scanning calorimetry (DSC), revealing the drug's existence in an amorphous state. Fourier transform infrared spectroscopy (FTIR) confirmed drug-excipient compatibility and the absence of interactions. Moreover, the flow properties of the extruded granules were analyzed to further assess their suitability for drug delivery applications. Therefore, the developed SEDDS formulation could be an effective oral delivery platform for simvastatin and could lead to better therapeutic outcomes.
Recommended Citation
Chilamula, Srikanth, "Formulation development of simvastatin self-emulsifying drug delivery system using Hot melt extrusion" (2024). Electronic Theses and Dissertations. 2799.
https://egrove.olemiss.edu/etd/2799