title: Study of the Lactobacillus rhamnosus Lcr35® properties after compression and proposition of a model to predict tablet stability.
abstract: The beneficial effects of probiotic bacteria on human health are now widely acknowledged, and this has prompted growing interest in research and development in the pharmaceutical field. However, to be viable when they reach their target, the bacteria must be able to survive during the manufacturing process and the biological pathway. Tablet form best meets the requirements for protecting acid labile drugs, but the tableting process could be an additional stress for the bacteria. This study evaluated the initial effect of compression pressure on the Lcr35® strain in a vaginal (Lcr regenerans®) and an intestinal (Lcr restituo®) formulation. A stability study was also performed on the tablets and revealed a beneficial effect of this form. The obtained destruction rates (k) demonstrated that the bacterial stability was greater in tablets than in powders (kpowders>ktablets). A new mathematical model was developed combining compression and temperature parameters to predict the bacterial viability at any pressure and time. Moreover, the genetic profile of Lcr35® (Rep-PCR, microarrays), its resistance to acidity and its ability to inhibit Candidaalbicans growth, after compression, were determined to evaluate the target product profile (TPP) in a Quality by Design (QbD) approach. The Rep-PCR analysis validated the strain identity and the microarrays demonstrated the genetic stability of Lcr35® strain after compaction. Additionally, ability to inhibit the C. albicans growth was maintained and the resistance to gastric conditions of Lcr35® was even improved by tableting. As a dosage form, tablets containing probiotic can guarantee that an adequate amount of bacteria reaches the therapeutic target (intestinal or vaginal) and that the product remains stable until the time of consumption.
authors.affiliation: Département Recherche et Développement - Probionov, Arpajon-sur-Cère, France; Université Paris Sud, UFR de Pharmacie, Laboratoire Matériaux et Santé EA401, Châtenay-Malabry, France. Electronic address: c.muller@probionov.com.
authors.forename: Claudia
authors.initials: C
authors.lastname: Muller
authors.affiliation: Université Paris Sud, UFR de Pharmacie, Laboratoire Matériaux et Santé EA401, Châtenay-Malabry, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Mazel
authors.affiliation: Département Recherche et Développement - Probionov, Arpajon-sur-Cère, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Dausset
authors.affiliation: Université Paris Sud, UFR de Pharmacie, Laboratoire Matériaux et Santé EA401, Châtenay-Malabry, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Busignies
authors.affiliation: IUT Clermont-Ferrand, Département Génie Biologique, Aurillac Cedex, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bornes
authors.affiliation: Département Recherche et Développement - Probionov, Arpajon-sur-Cère, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Nivoliez
authors.affiliation: Université Paris Sud, UFR de Pharmacie, Laboratoire Matériaux et Santé EA401, Châtenay-Malabry, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Tchoreloff
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D019245:Compressive Strength; D004355:Drug Stability; D005544:Forecasting; D052201:Lacticaseibacillus rhamnosus; D008962:Models, Theoretical; D019936:Probiotics / Q000737:chemistry*; D013607:Tablets
chemical_list: D013607:Tablets
keywords: Acid resistance; C. albicans; Destruction rate; Lactobacillus rhamnosus Lcr35®; Probiotic; Stability prediction; Tablet