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Title: Formulation and characterisation of novel films for buccal mucosa drug delivery for paediatric patients
Author: Khan, Sajjad
ISNI:       0000 0004 5366 9592
Awarding Body: University of Greenwich
Current Institution: University of Greenwich
Date of Award: 2015
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The main aim of this project was to develop, formulate, characterise and optimise novel pre-formed thin polymer film that will deliver therapeutically relevant drugs via the buccal mucosa route of paediatric patients, using OME as model drug. The development focused on obtaining formulations with optimized drug loading, drug release and permeation, stability and low toxicity. Five different film forming polymers hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), sodium alginate (SA), carrageenan (CA) and metolose (MET) were used initially and subsequently with polyethylene glycol (PEG 400) as plasticiser and L-arg (to stabilise OME). Polymeric gels (1% w/w) were prepared using water and ethanol (10% v/v and 20% v/v) as the casting solvents with PEG 400 at different concentrations (0 and 0.5 % w/w) and the films were obtained by drying the gels in an oven (40 °C). SA and MET films were chosen for drug loading and further investigation (OME stabilisation). These films showed a good balance between flexibility and toughness required for ease of transportation and patient handling. Drug loaded gels showed that OME was unstable, with gels turning red after 20 minutes and therefore required addition of L-arg. From the results obtained, plasticised (0.5 % w/w PEG 400) MET films prepared from ethanolic (20% v/v) gels and containing OME : L-arg ratio of 1:2 showed the most ideal characteristics (transparency, ease of peeling and flexibility) and was the formulation of choice for further investigation. Results obtained for the hydration and in vitro mucoadhesion studies showed that plasticised films had higher swelling capacity and mucoadhesivity than unplasticised films. In addition, BLK films showed higher swelling index and adhesion than DL films, whilst gelatine equilibrated with PBS showed higher values compared with simulated saliva (SS). Dissolution data from optimised DL MET films showed OME release was sustained over 1 hour. Fitting the release data to kinetic models showed that the Korsmeyer-Peppas equations best fit the dissolution data for both PBS and SS media. The permeability profile of optimised DL film using pig buccal tissue, showed that the amount of OME permeating over 2 hours was 275ug/cm2 suggesting that pig buccal membrane is generally quite permeable and also that the OME is released from the films. Application of SCF caused significant changes to the functional and physical properties of the MET films and converted the original DL MET films from a sustained release formulation (1 hour) to a rapid release system, releasing > 90% of OME within 15 minutes and the release of OME from these films followed Higuchi kinetic model. Finally, incorporation of β cyclodextrin (βCD) into DL MET films containing OME:L-arg 1:1, improved the stability of the drug over 28 days under ambient conditions compared to 14 days for the corresponding DL MET films containing only L-arg at a higher loading (OME: L-arg 1:2). The optimised formulations have potential as paediatric buccal delivery system for OME.
Supervisor: Boateng, Joshua ; Trivedi, Vivek Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RS Pharmacy and materia medica