Development and In-vitro Evaluation of a Probiotic-embedded Enteric Capsule for Simultaneous Antibiotic Delivery and Gut Microbiota Protection

Abstract

Antibiotic therapy remains indispensable for the treatment of bacterial infections; however, it frequently disrupts the intestinal microbiota, leading to antibiotic-associated dysbiosis and complications such as antibiotic-associated diarrhoea (AAD). Although probiotic supplementation has been widely recommended to restore microbial balance, conventional co-administration often results in poor probiotic survival during gastric transit and direct exposure to antibiotics, thereby reducing therapeutic effectiveness. The present study was designed to develop and evaluate a new dual-delivery enteric capsule system that achieves spatial and temporal separation of probiotic microorganisms from antibiotics within a single oral dosage form. Five probiotic strains were isolated from commercially available probiotic formulations (Lactobacillus rhamnosus GG, Bifidobacterium longum, Bacillus clausii, Bacillus coagulans and Saccharomyces boulardii) and characterised using morphological and biochemical methods. Susceptibility to amoxicillin, chloramphenicol, azithromycin and ciprofloxacin was determined using the broth macrodilution method over a concentration range of 0.06-256 µg/mL. Enteric-modified gelatin capsule shells containing probiotic cultures were prepared using hydroxypropyl methylcellulose phthalate (HPMCP), while antibiotics (250 mg) were separately encapsulated in the capsule core. The formulation was evaluated using a two-stage simulated gastrointestinal dissolution model comprising simulated gastric fluid (pH 2.5, 2 h), followed by simulated intestinal fluid (pH 6.8 containing 0.3% bile salts). The enteric capsule shells maintained their integrity during the gastric phase, preventing premature release of the antibiotics and probiotics. Slow disintegration of the capsules under intestinal conditions enabled controlled antibiotic release (around 65–83% in 120 min) and recovery of viable probiotic cells from the capsule matrix. Saccharomyces boulardii maintained high viability because of its intrinsic resistance to antibiotics, whereas Bifidobacterium longum showed reduced survival, consistent with its antibiotic susceptibility profile. Spectrophotometric estimation indicated reliable antibiotic quantification within the analytical calibration ranges. The results indicate the potential of an enteric dual-delivery capsule to protect probiotics during gastric transit and provide controlled antibiotic delivery in the intestine. Although further optimisation and in vivo validation are required, this formulation represents a promising microbiota-aware approach to improving antibiotic therapy and reducing antibiotic-associated dysbiosis.