Controlled Release Oral Dosage Forms Using Functional Additives in Hot Melt Extruded Pharmaceuticals

Alqahtani, Fahad (2021) Controlled Release Oral Dosage Forms Using Functional Additives in Hot Melt Extruded Pharmaceuticals. Doctoral thesis, University of East Anglia.

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Hot melt extrusion (HME) has been widely used for producing amorphous solid dispersions (ASD). There is an extensive body of literature on the pharmaceutical applications of solid dispersions produced by HME for improving the dissolution rates of poorly soluble drugs, but most systems are either binary polymer-drug or ternary polymer-drug-surfactant mixtures. There is still limited number of studies exploring the use of low quantities of functional additives in hot melt extruded solid dispersions to (1) tune the drug release rate from the formulations (for either immediate release or controlled release applications) and (2) to increase the drug loading capacity. The aim of this project is to develop fundamental understanding and formulation strategies in order to achieve these two new capabilities. Such knowledge has excellent potential to extend the application of solid dispersions for a much wider range of products.

Firstly, to develop tuneable drug release capability of ASD produced via HME, this project used carbamazepine as the model drug and HPMCAS as the base formulation and a range of low-quantity functional additives to investigate for their abilities to alter the drug release rate of the extrudates. We developed in depth understanding of the effects of these additives on the control of internal microstructure of HME extrudates. Secondly, to develop innovative approaches to increase the drug loading of ASD without compromising physical stability, we used tolbutamide as the model drug and Soluplus as the base formulation and mesoporous silica (MPS) as the functional additive. The results indicated the potential and limitations of MPS as a functional excipient for increasing drug loading in ASD prepared by HME. In this project, all hot melt extruded ASDs were characterised using conventional techniques including DSC, MTDSC, TGA, ATR-FTIR, PXRD, SEM, EDS, XμCT, in-vitro dissolution testing. Novel UV-imaging methodology was developed and performed on carbamazepine-loaded ASDs which facilitated the understand of the in-vitro dissolution behaviour of the ASDs.

The results of this project demonstrate the practicality of using low-quality functional additives in a single-step hot melt extrusion (HME) process to tune drug release behaviour and drug loading of ASDs which can bring new insights into the industrial applications of HME and ASDs.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Nicola Veasy
Date Deposited: 29 Nov 2022 11:15
Last Modified: 08 Dec 2022 10:29


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