Preparation and Evaluation of Aripiprazole-Loaded pH-Modulated Solid Dispersion via Hot-Melt Extrusion Technology

McFall, Haley (2016) Preparation and Evaluation of Aripiprazole-Loaded pH-Modulated Solid Dispersion via Hot-Melt Extrusion Technology. Undergraduate thesis, under the direction of Adam Smith from Chemical Engineering, University of Mississippi.


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The objective of this study was to prepare aripiprazole (ARI)-loaded solid dispersions (SDs) to enhance solubility and dissolution via hot-melt extrusion (HME) technology. ARI was chosen due to its poorly water-soluble properties. Solubility screenings of various polymers and acidifiers were performed to select appropriate excipients for the SD. Succinic acid (SA) and Kollidon 12 PF (PVP) were selected as the acidifier and the polymer, respectively. Differential scanning calorimetry and thermogravimetric analysis were used to determine the miscibility, interactions, and thermal stability of the drug and selected excipients. MODDE 8.0 is a design of experiment software that was implemented to produce several formulas that varied in screw speed and drug/polymer/acidifier ratios. The formulations were extruded using a twin-screw extruder and then milled into a fine powder using a laboratory grinder. Scanning electron microscopy and differential scanning calorimetry were used to perform solid-state characterizations of the pure drug and extrudates. The aqueous solubility and dissolution were then evaluated for the pure drug and milled extrudates. Each formulation showed increased solubility and dissolution compared to the crystalline ARI powder, which showed that HME is an advanced approach to enhance the dissolution and solubility of poorly soluble drugs. Since PVP was extrudable with ARI and SA, it appears to be a promising carrier for SDs with the poorly water-soluble drug using HME. Furthermore, the addition of an appropriate acidifier to the formulation has an important role on the solubility and dissolution of drug. The pH-modulated SD via HME could be used as a platform technology for solubilization of various poorly water-soluble drugs with pH-dependent solubility.

Item Type: Thesis (Undergraduate)
Creators: McFall, Haley
Student's Degree Program(s): B.S. Chemical Engineering
Thesis Advisor: Adam Smith
Thesis Advisor's Department: Chemical Engineering
Institution: University of Mississippi
Subjects: R Medicine > RM Therapeutics. Pharmacology
Depositing User: Haley McFall
Date Deposited: 25 Jan 2017 19:13
Last Modified: 25 Jan 2017 19:13

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