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The development of probiotics targeting non-intestinal body sites continues to generate interest amongst researchers, biotech companies and consumers alike. A key consideration for any bacterial strain to be developed into a probiotic is a robust assessment of its safety profile. Streptococcus salivarius strain M18 was originally isolated from a healthy adult and evaluated for its probiotic capabilities targeted to dental and oral health applications. This publication presents the safety characterisation of strain M18. Application of a diverse range of techniques showed that strain M18 can be specifically distinguished from other S. salivarius using a variety of molecular and phenotypic methodologies and that it lacks any relevant antibiotic resistance or virulence determinants. Direct comparison of the strain M18 safety profile with that of the prototype S. salivarius probiotic, S. salivarius strain K12, supports the proposition that strain M18 is indeed safe for probiotic application in humans.

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Penethamate (PNT) is an ester prodrug of benzylpenicillin which is marketed as dry powder for reconstitution with aqueous vehicle prior to injection. The purpose of this paper was to investigate the chemical stability of PNT in oily formulations to provide a basis for a ready-to-use (RTU) oil-based PNT formulation. The chemical stability of PNT solutions and suspensions in light liquid paraffin (LP), medium chain triglyceride (MIG), ethyl oleate (EO) and sunflower oil (SO) was investigated at 30 °C. Solid state stability of PNT powder and stability of PNT in EO suspensions with different moisture contents were also evaluated. The solubility of PNT in the oils was in order SO > EO > MIG > LP. Degradation of PNT was rapid in oily solutions and less than 10% remained after 7-15 days. Stability of PNT decreased with increase in moisture content in ethyl oleate suspensions. PNT was stable over four weeks in the solid state. Hydrolysis, due to moisture in the oil formulation is not the only degradation mechanism. PNT stability (% drug remaining) in oily suspensions after 3.5 months was in the order LP (96.2%) > MIG (95.4%) > EO (94.1%) > SO (86%). A shelf-life of up to 5.5 years at 30 °C may be achieved for PNT suspension in these oils.

Penethamate (PNT) is a diethylaminoethyl ester prodrug of benzylpenicillin used to treat bovine mastitis via the intramuscular route. Because of its instability, PNT products must be reconstituted before administration and the reconstituted injection has a short shelf life (7 days at 2-8°C). The purpose of this paper was to investigate whether the stability of PNT can be improved in order to achieve a chemically stable ready-to-use aqueous-based PNT formulation or at least to extend the shelf life of the reconstituted suspension. A chemical stability study of PNT in aqueous-based solutions as a function of pH, buffer strength, solvent mixtures and temperature, supported by studies of its solubility in mixed solvents, allowed predictions of the shelf life of PNT solution and suspension formulations. PNT degraded in aqueous solutions by several pathways over the pH range 2.0-9.3 with a V-shaped pH-rate profile and a minimum pH of around 4.5. The stability of PNT solutions in mixed solvents was greater than in aqueous solutions. For example, in propylene glycol:citrate buffer (60:40, v/v, pH 4.5), the half-life of PNT was 4.3 days compared with 1.8 days in aqueous buffer. However, solubility of PNT in the mixed solvent was higher than that in aqueous solution and this had an adverse effect on the stability of suspensions. By judicious choosing of pH and mixed solvent, it is possible to achieve a storage life of a PNT suspension of 5.5 months at 5°C, not sufficient for a ready-to-use product but a dramatic improvement in the storage life of the reconstituted product.

Bovine mastitis caused by bacterial infections of the mammary gland (udder) of dairy cows is a costly pathology for the dairy industry due to direct and indirect losses in production. Penethamate, a pro-drug of benzylpenicillin, is used by intramuscular injection (IM). The existing products are powders which must be reconstituted in water-for-injection and this presents difficulties in the field. Penethamate is too unstable to be formulated as an aqueous formulation but a chemically stable suspension formulation was possible in certain oils; however, some literature suggests that such formulations would have unacceptable prolonged release. The translational research proceeded iteratively from lab to the target species, rather than via laboratory animal trials. Pilot studies in cows suggested that some oily suspensions would give concentrations of benzylpenicillin, (in both blood and milk) comparable with those of the reconstituted product. A physicochemical screen and a low level in vitro-in vivo correlation (IVIVC) was cautiously used to guide selection of formulations for subsequent animal trials which have resulted in a lead formulation for good laboratory practices (GLP), good clinical practices (GCP) studies.

Probiotics developed for topical applications in humans have the potential to beneficially modulate microbial imbalances on the skin surface and thereby improve skin health. This study was conducted to determine whether topical formulations containing the human skin commensal Micrococcus luteus strain Q24 (BLIS Q24) are safe, tolerable and efficacious when used by healthy human subjects. M. luteus Q24 was assessed in vitro for haemolytic activity and its antibiotic susceptibility profile. Formulations of strain Q24 were evaluated for the preliminary safety and tolerability in healthy human participants. Forty-seven adults were randomly assigned to four single-site, single-blind randomised placebo or baseline controlled or active-controlled trials. Skin swab samples were collected for differential viable counts to monitor levels of probiotic colonisation. M. luteus Q24 was found to be non-haemolytic and susceptible to commonly used antibiotics. The M. luteus Q24 formulations were safe and tolerable and >90% of the participants reported improvements from baseline in the appearance (e.g., radiance and hydration) of their treated skin. Additionally, participants observed a reduction in pore size, skin clarity and enhanced skin softness. No adverse effects were reported. A dose-related significant increase was observed in the levels of M. luteus Q24 isolated from skin swabs of the probiotic-treated subjects. Placebo-controlled trials in human subjects involving the topical application of different doses of M. luteus Q24 formulations were supportive of the safety, tolerability and efficacy of probiotic M. luteus Q24. Self-reported skin health assessments by the subjects indicated that M. luteus Q24 has good potential as a probiotic for improving skin health quality.