Versatility of hot-melt extrusion for dosage form design

Recently, Hot Melt Extrusion (HME) has attracted the attention of pharmaceutical companies and scientists as a technique for manufacturing a variety of dosage forms. In this research, HME was applied in different ways to achieve different goals, such as solubility enhancement, taste masking, solid state stability enhancement, and sustained release formulations for oral drug delivery, using one model drug, mefenamic acid. For solubility enhancement and taste masking formulations, Eudragit EPO was blended with MA in different ratios (20, 25, 30, and 40% of drug loads) and processed by a hot melt extruder to produce a solid dispersion system. FT-IR analysis suggested hydrogen bonding between the drug and the carrier up to 25% drug loading. SEM images indicated aggregation of MA at over 30% drug loading. Based on the FT-IR, SEM, and dissolution results for the extrudates, two optimized formulations (20% and 25% drug loads) were selected to formulate orally disintegrating tablets (ODTs). ODTs were successfully prepared with excellent friability and rapid disintegration time, in addition to the desired taste-masking effect. In chapter 3, HME was applied to enhance the solubility of class II drugs by making solid dispersion systems by mixing MA with hydrophilic polymers (polyvinylpyrrolidone, PVP) in different ways as follow: (1) to demonstrate the effect of polyvinylpyrrolidone (PVP) matrices on the release of the poorly water-soluble drug, MA was prepared using the hot-melt extrusion technique, (2) to investigate the effect of PEG as a plasticizer and swelling agent in dissolution studies, (3) to study the influence of MgO as an alkalizer on the modification of the microenvironmental pH of the matrices, and (4) to investigate the combined effect of PEG and MgO on the drug release behavior of the formulations. In addition, we have also studied the ability of HME techniques to produce sustained release formulations for oral drug delivery. Various drug loads of MA and Kollidon® SR as a polymeric carrier were blended and extruded using a twin-screw extruder (16-mm Prism EuroLab, ThermoFisher Scientific) to prepare a solid dispersion system. Thermal analyses were used to confirm thermal stability, miscibility and to select the optimum processing conditions for extrusion. Sustained release tablets were successfully prepared with excellent tablet characteristics of these formulations. The drug release from the 40% drug-loaded extrudate reached 20% within 2 hours and 80% within 12 hours, compared to more than 80% drug release of the corresponding physical mixture, and 100% of the pure drug and formulations with higher drug loads of 60% and 80% within 2 hours. Therefore, the drug release of MA was further retarded by increasing the concentration of this polymer, which indicates Kollidon® SR has a significant effect on MA sustained release formulations.

Name thesis:degree_name

Ph.D. in Pharmaceutical Sciences

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biomolecular Sciences

Year dc:date.available

2015

Author dc:creator

• Alshehri, Sultan Mohammad

Contributors dc:contributor

• Michael A. Repka
• Samir A. Ross
• S. Narasimha Murthy

• Pharmacy and Pharmaceutical Sciences

Repository record dc:identifier

https://egrove.olemiss.edu/etd/1492

OAI identifier oai:identifier

oai:egrove.olemiss.edu:etd-2491