Formulation, Characterisation and Stabilisation of Buccal Films for Paediatric Drug Delivery of Omeprazole

Abstract

Abstract. This study aimed to develop films for potential delivery of omeprazole (OME) via the buccal mucosa of paediatric patients. Films were prepared using hydroxypropylmethylcellulose (HPMC), methylcellulose (MC), sodium alginate (SA), carrageenan (CA) and metolose (MET) with polyethylene glycol (PEG 400) as plasticiser, OME (model drug) and L-arg (stabiliser). Gels (1% w/w) were prepared at 40°C using water and ethanol with PEG 400 (0-1% w/w) and dried in an oven (40°C). Optimised formulations containing OME and L-arg (1:1, 1:2 and 1:3) were prepared to investigate the stabilisation of the drug. Tensile properties (Texture analysis, TA), physical form (differential scanning calorimetry, DSC; X-ray diffraction, XRD; thermogravimetric analysis, TGA) and surface topography (scanning electron microscopy, SEM) were investigated. Based on the TA results, SA and MET films were chosen for OME loading and stabilisation studies as they showed a good balance between flexibility and toughness. Plasticised MET films were uniform and smooth whilst unplasticised films demonstrated rough lumpy surfaces. SA films prepared from aqueous gels showed some lumps on the surface, whereas SA films prepared from ethanolic gels were smooth and uniform. Drug-loaded gels showed that OME was unstable and therefore required addition of L-arg. The DSC and XRD suggested molecular dispersion of drug within the polymeric matrix. Plasticised (0.5% w/w PEG 400) MET films prepared from ethanolic (20% v/v) gels and containing OME: L-arg 1:2 showed the most ideal characteristics (transparency, ease of peeling and flexibility) and was selected for further investigation.

Functional physico-chemical, ex vivo permeation and cell viability characterization of omeprazole loaded buccal films for paediatric drug delivery

“…The development of age appropriate formulations for paediatric populations is of current topical interest and buccal films have been proposed as suitable alternatives to traditional dosage forms such as tablets and liquids (Lui et al, 2014, Khan et al, 2015. An ideal and effective buccal dosage form is required to possess certain functional properties including 55 bioadhesion (mucoadhesion), hydration and swelling upon imbibing saliva, drug release from the swollen gel and eventual permeation through the buccal membrane .…”

“…In our previous publication (Khan et al, 2015) we showed that the drug which was added originally in crystalline form was present in amorphous form or molecularly dispersed within the film matrix. However, the dissolution profiles seem to 465 correlate with the swelling profiles suggesting that most of the release occurring in the first hour occurs via drug diffusion through the swollen gel.…”

“…The ratio of 1:2 for OME:L-arg was chosen because it was previously determined to be the optimum 240 concentration of the amino acid to prevent OME degradation whilst maintaining appropriate tensile properties (Khan et al, 2015). Before the dissolution studies, the content (assay) and uniformity of OME within the film was determined.…”

Conversion of sustained release omeprazole loaded buccal films into fast dissolving strips using supercritical carbon dioxide (scCO2) processing, for potential paediatric drug delivery

“…Its stability in aqueous solution is entirely dependent on the initial pH and, it is rapidly degraded in acidic and neutral conditions but shows greater stability in alkaline medium. We have previously shown the potential of OME based buccal films for sustained delivery of via the buccal mucosa for paediatric administration (Khan et al, 2015) and demonstrated the release and permeation of the drug 4 across pig buccal membrane (Khan et al, 2016). However, though OME is well absorbed from the gastrointestinal tract its oral bioavailability in humans of about 50% which suggests first pass metabolism for this drug.…”

Polysaccharide Based Formulations for Mucosal Drug Delivery: A Review

“…In a recent study, Khan and co-authors reported on novel solvent cast films prepared various hydrophilic polymers including the polysaccharides sodium alginate and carrageenan as well as metolose, hydroxypropylmethylcellulose and methylcellulose equivalent for the paediatric buccal delivery of the proton pump inhibitor omeprazole used in treating peptic ulcers [130]. Aqueous and ethanolic gels of both polymers were prepared and dried in an oven to obtain the films and the tensile properties determined to select optimum films for further analysis and drug loading.…”