The use of imaging in understanding the dissolution behaviour of Hypromellose and 3D printed compacts

Student thesis: Doctoral Thesis

Abstract

Controlled-release systems are created to produce a predictable, consistent plasma concentration level regardless of the biological environment at the site of application. The emergence of 3D printing has also proved to be a manufacturing route that takes patients need into consideration in providing patient-centred individual medicaments (personalised medicine). The main objectives of this thesis were to evaluate the micrometric and tabletting properties of the high viscosity K chemistry hypromellose polymer grades from various vendors and to examine the effect of hydro-alcoholic media on their matrix performance in a quest to determine if potentially interchangeable should there be supply issues. With the advent of 3D printing in exploring the potential of personalised as well as on-demand medicaments, fused deposition modelling (FDM) 3D printing was also investigated by exploring the probable use of polyvinyl alcohol (PVA) as a suitable filament for the printing process. This was conducted by investigating the effect of printed shell layers on a conventional tablet's dissolution behaviour and UV dissolution imaging. The results obtained from the study of these objectives suggested that the CR grades of the hypromellose K100M polymers displayed smaller particle size and better mechanical properties compared to their DC grade counterparts. The DC grades, however, had better flow properties than their CR counterparts. Statical factor analysis results confirmed that BonuCel D or Benecel XR under 7.5 kN, Methocel DC under 10 kN and Benecel DC under 12.5 kN will show similar properties overall. Despite the similarity in substitution level, suggesting that care and consideration should be given when a change is required or suggested. The CR and DC grade of Methocel was further evaluated to determine hydro-alcoholic effects on their performance. X-ray microtomography (XµT) and magnetic resonance imaging (MRI) were used as complementary techniques in determining the influence of the media composition on gel formation. The result showed that although differences were present in the gel layer thickness potentially due to differences in particle morphology, it did not significantly impact the dissolution process, especially in acidic and hydroalcoholic media. PVA was also successfully investigated as a filament for loading drug and being used to print three different infill percentage FDM 3D printing tablets. The impact of the infill percentages on the drug release was demonstrated via dissolution imaging. The 3D printing technique applied different thicknesses around the conventional tablets. UV dissolution imaging and in-vitro dissolution testing were employed to quantify the drug release behaviour from the different thicknesses of shell-printed tablets. 25% infill PAR 3D printing tablets followed the zero-order kinetic while 90% infill was fitted to the first-order kinetics. The UV dissolution imaging confirmed the effect of the shell on reducing the contact between the PPN conventional tablet and the dissolution media. 20 min dissolution profiles showed a 48.2 % drug release for the tablet alone, while 7T showed a 5.3 % drug release in acidic media. Where tablet alone fitted to Higuchi kinetics and 7T tablet fitted to the zero-order kinetics. The kinetics of the drug release confirmed the ability to increase the shell thickness allowed for the modification/manipulation of the kinetics model of drug release which can be beneficial for a patient.
Date of Award5 May 2023
Original languageEnglish
SupervisorKofi Asare-Addo (Main Supervisor), Karl Walton (Co-Supervisor), Kofi Asare-Addo (Co-Supervisor) & Karl Walton (Co-Supervisor)

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