Enteric coated spheres produced by extrusion/spheronization provide effective gastric protection and efficient release of live therapeutic bacteria

João M.S De Barros,Tabea Lechner,Dimitrios Charalampopoulos,Vitaliy V Khutoryanskiy,Alexander D Edwards

doi:10.1016/j.ijpharm.2015.06.051

João M.S De Barros, Tabea Lechner + Show 3 more

Open Access

https://doi.org/10.1016/j.ijpharm.2015.06.051

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Abstract

We present a novel but simple enteric coated sphere formulation containing probiotic bacteria (Lactobacillus casei). Oral delivery of live bacterial cells (LBC) requires live cells to survive firstly manufacturing processes and secondly GI microbicidal defenses including gastric acid. We incorporated live L. casei directly in the granulation liquid, followed by granulation, extrusion, spheronization, drying and spray coating to produce dried live probiotic spheres. A blend of MCC, calcium-crosslinked alginate, and lactose was developed that gave improved live cell survival during manufacturing, and gave excellent protection from gastric acid plus rapid release in intestinal conditions. No significant loss of viability was observed in all steps except drying, which resulted in approximately 1log loss of viable cells. Eudragit coating was used to protect dried live cells from acid, and microcrystalline cellulose (MCC) was combined with sodium alginate to achieve efficient sphere disintegration leading to rapid and complete bacterial cell release in intestinal conditions. Viability and release of L. casei was evaluated in vitro in simulated GI conditions. Uncoated spheres gave partial acid protection, but enteric coated spheres effectively protected dried probiotic LBC from acid for 2h, and subsequently released all viable cells within 1h of transfer into simulated intestinal fluid.

Highlights

Live bacterial cells (LBC) can be administered as pharmaceuticals, nutraceuticals or food supplements, with potential to treat and prevent disease or improve health (Cook et al, 2012)
Probiotics are defined by the World Health Organization (WHO) and the Food and Agriculture Organization (FAO) as “live microorganisms which when administered in adequate amounts confer health benefit on the host” with many proposed benefits (Bron et al, 2012; Fuller, 1991)
This can be attributed to protection of live cells by the excipients chosen, the calcium crosslinked alginate that it is believed to have maintained the integrity of the matrix, and/or the presence of lyoprotectants such as polysaccharides in the formulation such as lactose that could protect bacterial cells by stabilizing the osmotic 10 pressure and replacing water during drying (Bajaj et al, 2010; Ohtake and Wang, 2011)

Summary

Introduction

Live bacterial cells (LBC) can be administered as pharmaceuticals, nutraceuticals or food supplements, with potential to treat and prevent disease or improve health (Cook et al, 2012). After fermentation and harvest, a probiotic formulation starts with a cell density of 109 colony forming units (CFU) / mL or g or higher. This number typically suffers significant losses during manufacturing processes, where the most detrimental step is drying, due to osmotic and oxidative shock (Fu and Chen, 2011), but dehydration is necessary for long term preservation of live bacteria in solid oral doses (Morgan et al, 2006). After oral administration bacterial cells must survive the natural antimicrobial human defences, such as gastric juice, bile and enzymes (de Barros et al, 2014; Edwards and Slater, 2008, 2009; Solanki et al, 2013)

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