Multiple-unit tablet of probiotic bacteria for improved storage stability, acid tolerability, and in vivo intestinal protective effect

Abstract

Hee Jun Park,1 Ga Hyeon Lee,1 Joonho Jun,1 Miwon Son,1 Myung Joo Kang2 1Dong-A Pharmaceutical Co. Ltd., Yongin, Gyeonggi, 2College of Pharmacy, Dankook University, Cheonan, Chungnam, Korea Abstract: The aim of this study was to formulate probiotics-loaded pellets in a tablet form to improve storage stability, acid tolerability, and in vivo intestinal protective effect. Bacteria-loaded pellets primarily prepared with hydroxypropyl methylcellulose acetate succinate were compressed into tablets with highly compressible excipients and optimized for flow properties, hardness, and disintegration time. The optimized probiotic tablet consisted of enteric-coated pellets (335 mg), microcrystalline cellulose (Avicel PH102, 37.5 mg), and porous calcium silicate (25 mg) and allowed whole survival of living bacteria during the compaction process with sufficient tablet hardness (13 kp) and disintegration time (14 minutes). The multiple-unit tablet showed remarkably higher storage stability under ambient conditions (25°C/60% relative humidity) over 6 months and resistance to acidic medium compared to uncoated strains or pellets. Repeated intake of this multiple-unit tablet significantly lowered plasma level of endotoxin, a pathogenic material, compared to repeated intake of bare probiotics or marketed products in rats. These results, therefore, suggest that the multiple-unit tablet is advantageous to better bacterial viability and gain the beneficial effects on the gut flora, including the improvement of intestinal barrier function. Keywords: probiotics, multiple-unit tablet, bacterial viability, acid resistance, intestinal barrier function

Keywords

• probiotics
• multiple-unit tablet
• storage stability
• acid tolerability
• intestinal protection