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The Delivery of Porous Poly (DL-Lactide-co-Glycolide) Microspheres Via Pressurised Metered Dose Inhaler Suspensions

Cocks, Elizabeth Ann; (2003) The Delivery of Porous Poly (DL-Lactide-co-Glycolide) Microspheres Via Pressurised Metered Dose Inhaler Suspensions. Doctoral thesis (Ph.D), UCL (Uiversity College London). Green open access

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Abstract

This thesis covers an area of the pharmaceutical industry that has received extensive interest in recent years, pulmonary drug delivery using biodegradable microspheres as carriers of peptides and proteins. The most common method of pulmonary administration is via a pressurised metered dose inhaler (pMDI). There has been extensive interest in the pulmonary delivery of peptides and proteins, especially with the use of relatively large porous microspheres. This work investigates the feasibility of delivering large (≈ 25 μm) porous poly (lactide- co-glycolide) (PLGA) microspheres containing a model protein via pMDI. Microspheres were prepared using a double emulsion solvent evaporation technique manipulating the primary emulsion phase characteristics to produce microspheres of varying morphology, size, encapsulation efficiency and release characteristics. Porous microspheres were then prepared as pMDI suspension based systems containing 'alternative' stabilising agents in 1,1,1,2 tetrafluoro ethane (HFA 134a) and 1,1,1,2,3,3,3-heptafluoropropane (HFA 227). The use of ethanol was also investigated to prepare stable pMDI suspensions. The physical stability of the suspension was assessed by visual and optical suspension characterisation. Aerosolisation characteristics were investigated using aerosol particle sizing dose delivery through the valve and shot weight. The results show physical suspension stability was not achieved when preparing pMDIs in HFA 134a due to rapid sedimentation. When employing HFA 227 an optimum concentration of stabilising agent was required to achieve physical suspension stability; formulations that exhibited good physical stability also showed optimum aerosolisation characteristics. An optimum concentration of ethanol was also required to achieve both physical suspension stability and optimum aerosolisation characteristics. In conclusion, manipulation of the double emulsion method for the preparation of microspheres produces microspheres of varying morphology, size, encapsulation efficiency and release characteristics. In addition, porous PLGA microspheres (≈ 25 μm) show potential as antigen carrier and also to target lower regions of the lungs when prepared as pMDI suspension formulations.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The Delivery of Porous Poly (DL-Lactide-co-Glycolide) Microspheres Via Pressurised Metered Dose Inhaler Suspensions
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences; Delivery; Dl-lactide-co-glycolide; Dose; Glycolide; Inhaler; Lactide; Metered; Microspheres; Porous; Pressurised; Suspensions
URI: https://discovery.ucl.ac.uk/id/eprint/10101238
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