Multiple-unit tablet of probiotic bacteria for improved storage stability, acid tolerability, and in vivo intestinal protective effect.
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.
Dong-A Pharmaceutical Co. Ltd., Yongin, Gyeonggi, Korea.
Hee Jun
HJ
Park
Dong-A Pharmaceutical Co. Ltd., Yongin, Gyeonggi, Korea.
Ga Hyeon
GH
Lee
Dong-A Pharmaceutical Co. Ltd., Yongin, Gyeonggi, Korea.
Joonho
J
Jun
Dong-A Pharmaceutical Co. Ltd., Yongin, Gyeonggi, Korea.
Miwon
M
Son
College of Pharmacy, Dankook University, Cheonan, Chungnam, Korea.
Myung Joo
MJ
Kang
D000143:Acids / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D017610:Calcium Compounds / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D004356:Drug Storage; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007422:Intestines / Q000187:drug effects* / Q000382:microbiology; D007778:Lactobacillus / Q000737:chemistry; D019936:Probiotics / Q000008:administration & dosage* / Q000737:chemistry*; D020011:Protective Agents / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017640:Silicates / Q000737:chemistry; D013607:Tablets
D000143:Acids; D017610:Calcium Compounds; D004731:Endotoxins; D020011:Protective Agents; D017640:Silicates; D013607:Tablets; C031293:calcium silicate
acid resistance; bacterial viability; intestinal barrier function; multiple-unit tablet; probiotics