Date of Award
1-1-2022
Document Type
Dissertation
Degree Name
Ph.D. in Pharmaceutical Sciences
First Advisor
Michael Repka
Second Advisor
Eman Ashour
Third Advisor
Walt Chambliss
School
University of Mississippi
Relational Format
dissertation/thesis
Abstract
Hot melt extrusion technology has been prevalent in the pharmaceutical industry for the mixing, compounding and processing of materials. Due to the adaptability and versatility of the twin screw extruder, the hot melt extrusion process has been widely used as a manufacturing tool in formulation and product development. Hot melt extrusion being a continuous manufacturing process has several advantages in comparison to the batch manufacturing process, thus being explored for different applications and for the development of diverse dosage forms. The conventional formulation techniques have limitations due to the use of large amount of solvents and challenges for scaling up.
The aim of the research was to explore different dosage forms prepared by hot melt extrusion technology for oral delivery thereby understanding the impact of process and formulation parameters on the developed product. Taste masking for immediate release, twin screw melt granulation for extended release and amorphous solid dispersions for the dissolution enhancement of poorly soluble drug by hot melt extrusion technology was explored. Inclusion of lipids and polymers as excipients were extensively studied in the formulation design.
The potential of various lipids in masking the bitter taste of the model API-caffeine citrate by hot melt extrusion technology was investigated. Extruded granules containing high drug loadings with different lipids such as Compritol® 888 ATO and Precirol® ATO 5 were prepared by using a 11mm co-rotating twin-screw extruder. Dissolution studies in pH-6.8 showed a decrease in drug release at the end of 2 min in comparison to the pure caffeine citrate demonstrating the taste masking efficiency of the incorporated lipids. The influence of different solubilizers such as Gelucire ® 48/16, Gelucire ® 50/13 and poloxamer 188 was explored to assess the drug release in 0.1N HCl.
Twin screw melt granulation was employed for a lipid-based matrix tablet with polymeric binders for an extended release application. Quetiapine fumarate as the model API was extruded as granules using 11mm co-rotating twin-screw extruder (Process 11 twin screw extruder, Thermo Fisher Scientific) utilizing a modified screw configuration at 30% drug loading with Gelucire® 43/01 lipid as the retarding agent along with Klucel ™ EF and Plasdone ™ S630 Ultra as polymeric binders. The binder concentrations were varied from 5%-15% (w/w). Avicel ® PH 101 was also added during the extrusion process. The granules were compressed into tablets and characterized for in vitro drug release, water uptake and matrix erosion studies. Outcome of dissolution results showed Klucel ™ EF formulations extended the release of the API over 24h with water uptake and erosion studies corroborating the dissolution results due to the increased viscosity and high molecular weight of Klucel™ EF as binder.
Determination of process parameters of a product during hot melt extrusion process is vital for the operation of continuous processes. An immediate release hot melt extruded pellets containing the poorly aqueous soluble drug indomethacin with five different screw configurations was developed for oral application. Numerical simulation with respect to residence time was performed for each configuration to give valuable tool for better process understanding and ease of scale-up. The pellets were prepared using immediate release matrix forming polymers such as Kollidon® and Soluplus® by coupling hot melt extrusion with a die-surface cutting pelletizer into 1.5 mm pellets. In vitro release studies demonstrated that the indomethacin dissolution rate was improved significantly from both polymeric matrices for all the tested screw configurations as compared with the bulk drug. The numerical simulation studies did not show significant difference between predicted and experimental extrusion residence time for only four screw configurations. In conclusion, hot melt extrusion can be considered as an efficient, scalable, and a solvent-free process for the manufacture of different dosage forms for distinct applications and a potential alternative for the common techniques.
Recommended Citation
SRINIVASAN, PRIYANKA, "Preparation of different dosage forms utilizing hot melt extrusion technology for oral delivery" (2022). Electronic Theses and Dissertations. 2460.
https://egrove.olemiss.edu/etd/2460
Concentration/Emphasis
Pharmaceutical Science