Romain Caillard

β-Lactoglobulin tablets as a suitable vehicle for protection and intestinal delivery of probiotic bacteria

The use of succinylated β-lactoglobulin as a novel functional tablet excipient for the protection of probiotic bacteria against the adverse gastric conditions and their delivery in the intestine was studied. Tablets were produced by direct compression of a dry mixture of Bifidobacterium longum HA-135 and the tested excipient. The results showed that tablets made of native β-lg did not ensure cell survival while grafting carboxylic acid groups on the protein revealed to be an innovative method to create a gastroresistant matrix that could allow the survival of up to 10(8)CFU and 10(7)CFU after 1h and 2h gastric incubation, respectively. When compared to other polymers, succinylated β-lg promoted the best survival both upon compression and after simulated gastric passage. The proportion of succinylated β-lg in the formulation could be lowered to 60% without modifying the protective ability of the matrix. Additionally, the tablets proved to be stable over a period of 3 months when refrigerated. Succinylated β-lg tablets are an interesting vehicle for the protection of acid-sensitive bacteria during transit in the upper gastro-intestinal tract.

Protein based tablets as reversible gelling systems for delayed release applications

Succinylated β-lactoglobulin (S-β-lg) was previously shown to be efficient as new excipient for the formation of enteric tablets, suitable for several applications including probiotics delivery. This work investigates the mechanisms leading to S-β-lg tablets delayed release. Release kinetics were evaluated in vitro. Fourier transformed infra red spectroscopy (FTIR) was used to visualize the effect of dissolution medium on matrix tablet surface. Results demonstrated that tablets release in simulated gastric fluids (SGF) might be due to water/drug diffusion through an in situ formed gel layer, as revealed by FTIR data. As SGF penetrated the tablet, regardless of protein succinylation rate (50% or 100%), molecular rearrangements occurred, allowing the development of an important band located in the 1621-1623 cm(-1) region. This band was characteristic of the formation of protein intermolecular β-sheets. The gel was showed to be reversible in intestinal conditions, allowing delayed release. While the molecular structure of the gel layer was not depending on protein succinylation rate, it appeared that 100% S-β-lg tablets showed slower release. This low release was probably related to 100% S-β-lg lower solubility, lower charge density, and their ability to form stronger intermolecular hydrogen bonds. This work highlights proteins potential for the conception of controlled drug delivery systems.

In vitro gastric survival of commercially available probiotic strains and oral dosage forms

Although the intestinal microbial community is still incompletely understood, there is strong evidence of the benefits of using probiotics to address some medical states or conditions. As a result, the probiotics oral supplements market has exploded during the last few years. However, while their sensitivity to gastric juices, acidic pH and bile is well known, most of these oral forms would not guarantee any survival of the strains in such conditions. In this work, we have studied the resistance to simulated gastric juices of several commercially available probiotics products. These included sixteen strains and ten oral forms such as enteric/non-enteric capsules/tablets and microencapsulated strains. Results demonstrated that all tested strains showed high sensitivity to acidic conditions and suggested that most of these microorganisms would not show any viability when immersed in the stomach at fasting. Most probiotics oral forms did not provide any protection to strains, unless these forms presented strong enteric protection. Consequently, the efficacy of non-enteric products to fully provide to the patient the benefits related to the consumption of probiotics supplement would be strongly questionable. This study underlines the chasm between the current opinion about probiotics protection needs and the products proposed by many companies in the dietary supplements area.