Affiliation:
1. Department of Chemical Engineering, Loughborough University, Loughborough LE11 3TU, UK
Abstract
This study addresses the challenge of developing a cheap, patient-friendly alternative to antibiotics using bacteriophages for gastrointestinal applications. It explores the feasibility of manufacturing an enteric solid dosage form containing a salmonella-specific Myoviridae phage, Felix O1, encapsulated in spray-dried trehalose/Eudragit microparticles. The spray-dried powder was further formulated by combining the spray-dried microparticles with magnesium stearate to facilitate the fabrication of tablets using direct compression. The paper presents a comprehensive evaluation of the tablets with measurements of phage viability during tablet fabrication using a range of compression settings and, after tablet disintegration, dissolution and friability. Phage viability measurements were performed using storage stability testing of spray-dried powders and tablets in sealed vials at 4 °C, 20 °C and 30 °C and under different humidity conditions of 0%, 50% and 65% RH. The recommended compression force range was found to be 10–15 kN for a standard 10 mm diameter tablet. The storage of tablets at 4 °C/0% RH was found to be the most favourable condition resulting in a ~1 log loss in titre over a six-month storage period. Storage at higher temperatures and samples exposed to high levels of humidity resulted in a significant loss in phage viability. The paper highlights challenges in developing phage formulations suitable for direct-compression tableting, which afford the phages protection when exposed to temperatures and humidity levels that do not require a cold supply chain.
Funder
UK Engineering and Physical Sciences Research Council
Subject
Process Chemistry and Technology,Chemical Engineering (miscellaneous),Bioengineering
Reference28 articles.
1. Intussusception-related Hospitalizations Among Infants Before and After Private Market Licensure of Rotavirus Vaccines in Taiwan, 2001–2013;Yen;Pediatr. Infect. Dis. J.,2017
2. Bacteriophage Therapy;Sulakvelidze;Antimicrob. Agents Chemother.,2001
3. Antibiotics and bacterial resistance in the 21st Century;Fair;Perspect. Med. Chem.,2014
4. The global problem of childhood diarrhoeal diseases: Emerging strategies in prevention and management;Mokomane;Ther. Adv. Infect. Dis.,2018
5. Antibiotic resistance—A rundown of a global crisis;Aslam;Infect. Drug Resist.,2018