A Dual-Biotic System for the Concurrent Delivery of Antibiotics and Probiotics: In Vitro, Ex Vivo, In Vivo and In Silico Evaluation and Correlation.

Purpose: A delayed release bio-polymeric Dual-Biotic system has been extensively evaluated in this study to overcome the therapeutic issue of probiotic killing due to incorrect administration with the antibiotic.

Methods: In vitro and ex vivo release and characterization studies have been undertaken on the Dual-Biotic system. In vivo analyses utilizing a Large White pig model were also performed with commercial products used as a comparison. Intestinal fluid for probiotic quantification was aspirated using a surgically implanted intestinal cannula with Lactobacillus acidophilus cell counts determined through luminescence and inoculation onto Lactobacilli-specific agar. Plasma amoxicillin concentrations were determined through Ultra-Performance Liquid Chromatography. The reactional profile and crosslinking mechanism of ovalbumin and genipin was elucidated using molecular mechanic energy relationships in a vacuum system by exploring the spatial disposition of different concentrations of genipin with respect to ovalbumin with ovalbumin/genipin ratios of 1:1, 1:5 and 1:10.

Results: In vivo evaluation of the Dual-Biotic system detailed maximum Lactobacillus viability (~455% baseline viability) 6 h after oral administration. Concurrent administration of the commercial products revealed a 75% decrease in bacterial viability when compared to the controls analyzed. A level A in vitro-in vivo correlation was also established with 96.9% predictability of amoxicillin release ascertained. The computational results achieved corroborated well with the experimental findings and physicochemical data.

Conclusions: Evaluation and correlation of the Dual-Biotic system has detailed the success of the formulation for the concurrent delivery of an antibiotic and probiotic.