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

Abstract

25Buccal films were prepared from aqueous and ethanolic Metolose gels using the solvent casting approach (40°C). The hydration (PBS and simulated saliva), mucoadhesion, physical stability (20°C, 40°C), in vitro drug (omeprazole) dissolution (PBS and simulated saliva), ex vivo permeation (pig buccal mucosa) in presence of simulated saliva, ex vivo bioadhesion and cell viability using MTT of drug loaded (DL) films were investigated. Hydration and mucoadhesion 30 results showed that swelling capacity and adhesion was higher in the presence of PBS than simulated saliva (SS) due to differences in ionic strength. Omeprazole was more stable at 20°C than 40°C whilst omeprazole release reached a plateau within 1 hour and faster in PBS than in SS. Fitting release data to kinetic models showed that Korsmeyer-Peppas equation best fit the dissolution data. Drug release in PBS was best described by zero order via non-Fickian 35 diffusion but followed super case II transport in SS attributed to drug diffusion and polymer erosion. The amount of omeprazole permeating over 2 hours was 275ug/cm 2 whilst the formulations and starting materials showed cell viability values greater than 95%, confirming their safety for potential use in paediatric buccal delivery.

Development and functional characterization of composite freeze dried wafers for potential delivery of low dose aspirin for elderly people with dysphagia

“…In figure 4 c it can be observed that the MET:CAR 1:1 and 3:1 wafers (samples B1, B2, C1 and C2) had longer swelling duration of about 120 minutes and lower swelling capacity which is due to the higher concentrations of MET which act as a stabilizer for the wafers (Shin Etsu Chemical, 2005). In SS the swelling profile of MET:CAR 3:1,1:1 and 1:3 (samples A1, B1, C1, A2, B2 and C2) were lower than when performed in PBS (Figure 4d) which could be due to the difference in ionic strength of the media and that plays an important role in the swelling of the wafers (Khan, et al, 2016).…”

“…MET is a non-ionic cellulose ether composed of methylcellulose and three types of HPMC which are available in different grades with varying viscosities. The most important properties of MET includes solubility in cold water, development of transparent solutions and viscoelastic properties (Khan, et al, 2016).…”

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.…”

“…In previous studies (Khan et al, 2015(Khan et al, , 2016, we developed mucoadhesive and sustained release MET based films incorporating OME as a model drug and L-arg as stabilising agent to prevent drug degradation. Functional characterisation showed release of the drug and subsequent permeation through pig buccal tissues over a two hour period, owing to prolonged retention at the buccal mucosa surface.…”

“…Different studies report a residence time and ideal release period ranging from 2 -6 hours Figueiras et al, 2009;Khan et al, 2015;Trastullo et al, 2016) with the maximum usually between 4 -6 hours. We opted for the lower time period of 2 hours (Khan et al, 2015(Khan et al, , 2016, taking into consideration the expected difficulty of retaining formulations in the buccal region of paediatric patients for prolonged periods, for example challenges such as feeding and tongue movements. This study has shown that treatment of the sustained release films with scCO2 changed them into rapid release formulations as observed in the results above.…”