A study of magnesium stearate behaviour in pharmaceutical blends and tablets employing Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS)

Peddapatla, Raghu V. G.

A study of magnesium stearate behaviour in pharmaceutical blends and tablets employing Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS)

dc.check.chapterOfThesis	3, 4, 6, 7
dc.check.date	2023-02-25T13:44:10Z
dc.check.embargoformat	Apply the embargo to both hard bound copy and e-thesis (If you have submitted an e-thesis and a hard bound thesis and want to embargo both)	en
dc.check.info	Restricted to everyone for three years	en
dc.check.opt-out	Not applicable	en
dc.check.reason	This thesis is due for publication or the author is actively seeking to publish this material	en
dc.contributor.advisor	Crean, Abina	en
dc.contributor.advisor	Sousa Gallagher, Maria J	en
dc.contributor.author	Peddapatla, Raghu V. G.
dc.contributor.funder	Enterprise Ireland	en
dc.contributor.funder	Science Foundation Ireland	en
dc.date.accessioned	2020-02-26T13:44:10Z
dc.date.issued	2019
dc.date.submitted	2019
dc.description.abstract	Magnesium Stearate (MgSt) is the most commonly used lubricant in pharmaceutical industries. Effects of MgSt on the final product have been extensively studied in batch processing. In recent times pharmaceutical companies have been increasingly interested in continuous processing, where the relative effects of material properties and process parameters on blend behaviour during continuous processing has gained significant attention. It is important to assess the behaviour of materials and it is a challenging feat to monitor behaviour of very cohesive materials like MgSt in continuous processing. The main aims of this thesis were, to investigate the role of MgSt supplier variability during continuous feeding through a loss in weight feeder (LIW) and to investigate the capability of Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS) to discriminate between blends and tablets with variable MgSt distribution. Initially, the variability among four different grades of MgSt samples from two different suppliers was studied. The variability among the samples was evident (chapter-3) and the effect of this variability on continuous feeding performance of MgSt samples was studied (Chapter-4). Bulk density of the samples dictated the feed factor achieved for the MgSt samples, when fed through K-Tron MT12 feeder (Chapter-4). Higher variability in the feed rate RSD was noticed for the MgSt samples, when fed at lower feed rate of 0.15 kg/hr and for samples (Ligamed MF-2- V and Ligamed MF-2-V-BI) with similar properties. Post feeding characterisation of MgSt samples was performed to identify any effect of feeding on particulate properties. A reduction in particle size due to feeding of the samples was noted and these samples when included in tablet blends, showed a delayed drug release, which was more prominent in tablets with fed MgSt of Alfa Aesar and Ligamed MF2-V samples. Ligamed MF-3-V was least effected by feeding and when fed samples were included in formulations a very slight delay in drug release was noted compared to other tablets with other MgSt samples (Chapter-4). A novel technology, BARDS was employed for the first time to analyse the excipients, tablet blends and tablets (Chapter-5 and Chapter-6). Analysis of unlubricated and lubricated blends using BARDS, clearly discriminated between the blends, resulting inan extended acoustic response for lubricated blends. K-Tron MT12 feeder, was used to feed the unlubricated and lubricated blends at three different feed rates (0.2238 kg/hr, 0.5594 kg/hr and 1.006 kg/hr), anticipating lubricated blend with varied degrees of blend lubrication. When analysed using BARDS, unlubricated blend fed at increasing feed rates showed similar acoustic response, whereas lubricated blend showed extended acoustic response, which was dependent on the feed rate (Chapter-5). Gas elimination rate constant was used to determine the degree of lubrication within blends. The degree of overlubrication was further confirmed by the standard wetting techniques and tabletability of the blends (Chapter-5). Tablets were produced from unlubricated and lubricated blends at a compression pressure range of 30 MPa to 234 MPa. The influence of compression pressure and tablet properties, on the BARDS acoustic response was investigated in Chapter-6. The yield pressures calculated from the Heckel analysis was 98 MPa and 102 MPa for unlubricated and lubricated tablets. A significant change in the BARDS acoustic response was noticed for tablets produced above and below yield pressure for both blends. Lubricated tablets produced at higher compression pressures, showed delamination, which was identified by BARDS. Slow gas elimination rate constant was observed for lubricated tablets compared to unlubricated tablets.	en
dc.description.status	Not peer reviewed	en
dc.description.version	Accepted Version
dc.format.mimetype	application/pdf	en
dc.identifier.citation	Peddapatla, R. V. G. 2019. A study of magnesium stearate behaviour in pharmaceutical blends and tablets employing Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS). PhD Thesis, University College Cork.	en
dc.identifier.endpage	206	en
dc.identifier.uri	https://hdl.handle.net/10468/9699
dc.language.iso	en	en
dc.publisher	University College Cork	en
dc.relation.project	Enterprise Ireland (Pharmaceutical Manufacturing Technology Centre Grant: TC 2013-0015)	en
dc.relation.project	info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2275/IE/Synthesis and Solid State Pharmaceutical Centre (SSPC)/	en
dc.rights	© 2019, Raghu V. G. Peddapatla.	en
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/	en
dc.subject	Lubrication	en
dc.subject	Broadband Acoustic Resonance Dissolution Spectroscopy	en
dc.subject	BARDS	en
dc.subject	Magnesium stearate	en
dc.subject	Continuous processing	en
dc.subject	Continuous feeding	en
dc.thesis.opt-out	false
dc.title	A study of magnesium stearate behaviour in pharmaceutical blends and tablets employing Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS)	en
dc.type	Doctoral thesis	en
dc.type.qualificationlevel	Doctoral	en
dc.type.qualificationname	PhD	en
ucc.workflow.supervisor	a.crean@ucc.ie