Determination of Honey Varietals’ Impact on Bifidobacterium animalis ssp lactis Survivability in Commercial Yogurt Through Simulated In Vitro Digestion

Objectives Consumption of yogurt containing the probiotic Bifidobacterium animalis lactis DN-173 010/CNCM I-2494 (B. animalis) improves digestive health and quality of life in adults. To optimize the benefits of this probiotic, we aimed to test our hypothesis that yogurt with honey would increase the survivability of B. animalis under simulated gastrointestinal tract digestion conditions. Methods Phase 1 tested four honey varietals (alfalfa, buckwheat, clover, and orange) at a final concentration of 20% w/w in yogurt containing B. animalis. Undiluted yogurt and yogurt with added sucrose or water (20% w/w) were included as control treatments. Phase 2 assessed clover honey at final concentrations of 20, 14, 10, 9, 8, 6, 4% w/w. Yogurt samples were subjected to in vitro simulated oral, gastric, and intestinal digestion using simulated salivary, gastric, and intestinal fluids, respectively. At four time points—pre-digestion, and after each phase of digestion (oral, gastric, intestinal)—probiotic cells were enumerated first by spread plating on MRS agar and incubated for 5 h at 37°C under anaerobic conditions. Then, plates were overlaid with MRS supplemented with lithium chloride and sodium propionate and incubated an additional 67 h prior to quantification of the probiotic colony forming units (CFU). Results Phase 1 demonstrated similar probiotic counts between honey varietals and controls after exposure to oral and gastric simulated fluids (< 1 Log CFU/g of probiotic reduction after gastric phase). There was comparable probiotic survival after the simulated intestinal phase for yogurt with the alfalfa, buckwheat, and orange honey varietals relative to control yogurt treatments. However, higher B. animalis survivability was observed in yogurt with clover honey after exposure to simulated intestinal fluids (∼3.5 Log CFU/g reduction) compared to all control treatments (∼5.5 Log CFU/g reduction, P ˂ 0.05). Phase 2 revealed that 20%, 14% and 10% w/w clover honey similarly supported B. animalis survivability after exposure to simulated intestinal fluids. Conclusions These results demonstrated that clover honey increased B. animalis survivability in yogurt during in vitro digestion when provided at doses equivalent to 1 to 2 tablespoons per serving (170g) of yogurt. Funding Sources The National Honey Board.

Effects of Transport Medium Composition on in vitro Drug Permeation across Excised Pig Intestinal Tissue

Background:: Knowledge of the permeation characteristics of new chemical entities across biological membranes is essential to drug research and development. Transport medium composition may affect the absorption of compounds during in vitro drug transport testing. To preserve the predictive values of screening tests, the possible influence of transport media on the solubility of model drugs, and on the activities of tight junctions and efflux transporter proteins (e.g. P-glycoprotein) must be known. Objective:: The aim of this study was to compare the impact of different transport media on the bi-directional transport of standard compounds, selected from the four classes of the Biopharmaceutical Classification System (BCS), across excised pig intestinal tissue. Methods:: The Sweetana-Grass diffusion apparatus was used for the transport studies. Krebs-Ringer bicarbonate (KRB) buffer and simulated intestinal fluids in the fed (FeSSIF) and fasted (FaSSIF) states were used as the three transport media, while the chosen compounds were abacavir (BCS class 1), dapsone (BCS class 2), lamivudine (BCS class 3) and furosemide (BCS class 4). Results:: Abacavir exhibited lower permeability in both the simulated intestinal fluids than in the KRB buffer. Dapsone showed similar permeability in all media. Lamivudine exhibited lower permeability in FaSSIF than in the other two media. Furosemide exhibited improved transport with pronounced efflux in FaSSIF. Conclusion:: Different permeation behaviors were observed for the selected drugs in the respective media, which may have resulted from their different physico-chemical properties, as well as from the effects that dissimilar transport media components had on excised pig intestinal tissue.

Intrinsic Dissolution Rate Profiling of Poorly Water-Soluble Compounds in Biorelevant Dissolution Media

The intrinsic dissolution rate (IDR) of active pharmaceutical ingredients (API) is a key property that aids in early drug development, especially selecting formulation strategies to improve dissolution and thereby drug absorption in the intestine. Here, we developed a robust method for rapid, medium throughput screening of IDR and established the largest IDR dataset in open literature to date that can be used for pharmaceutical computational modeling. Eighteen compounds with diverse physicochemical properties were studied in both fasted and fed state simulated intestinal fluids. Dissolution profiles were measured in small-scale experimental assays using compound suspensions or discs. IDR measurements were not solely linked to API solubility in either dissolution media. Multivariate data analysis revealed that IDR strongly depends on compound partitioning into bile salt and phospholipid micelles in the simulated intestinal fluids, a process that in turn is governed by API lipophilicity, hydrophobicity, and ionization.

An investigation of PS-b-PEO polymersomes for the oral treatment and diagnosis of hyperammonemia

Ammonia-scavenging transmembrane pH-gradient poly(styrene)-b-poly(ethylene oxide) polymersomes were investigated for the oral treatment and diagnosis of hyperammonemia, a condition associated with serious neurologic complications in patients with liver disease as well as in infants with urea cycle disorders. While these polymersomes were highly stable in simulated intestinal fluids at extreme bile salt and osmolality conditions, they unexpectedly did not reduce plasmatic ammonia levels in cirrhotic rats after oral dosing. Incubation in dietary fiber hydrogels mimicking the colonic environment suggested that the vesicles were probably destabilized during the dehydration of the intestinal chyme. Our findings question the relevance of commonly used simulated intestinal fluids for studying vesicular stability. With the encapsulation of a pH-sensitive dye in the polymersome core, the local pH increase upon ammonia influx could be exploited to assess the ammonia concentration in the plasma of healthy and cirrhotic rats as well as in other fluids. Due to its high sensitivity and selectivity, this novel polymersome-based assay could prove useful in the monitoring of hyperammonemic patients and in other applications such as drug screening tests.Graphical abstract

Potential Use of the Maillard Reaction for Pharmaceutical Applications: Gastric and Intestinal Controlled Release Alginate-Albumin Beads

In this study, bovine serum albumin (BSA) and alginate (ALG) conjugates were synthesized by the Maillard reaction in order to evaluate their potential to develop controlled release drug delivery systems. The progress of the Maillard reaction was evidenced using ultraviolet (UV) absorbance, determination of BSA remaining free amino groups, and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). BSA-ALG conjugates possessed enhanced and tunable viscosity, foamability and foam stability. Foam generated from BSA-ALG conjugate solution was used to prepare floating gastroretentive calcium ALG beads. Unlike traditional ALG beads, BSA-ALG foam beads were able to float and sustain the ciprofloxacin (CIP) release in gastric medium. Interestingly, intestinal beads made of ALG, BSA-ALG physical mixture and BSA-ALG conjugate resulted in different release rates and orders of indomethacin (IND) in simulated intestinal fluids; while beads based on a physical mixture of BSA-ALG resulted in a first order sustained release profile, both systems based on ALG and BSA-ALG conjugate displayed zero order sustained release profiles with IND being released at a slower rate from the conjugate beads.

Synthesis Of Mesoporiic Silica From Rice Husk Ash For Pinostrobin Based Drug Delivery

A study has been conducted on the synthesis of mesoporous silica as introductory material pinostrobin anticancer compounds. The aim of this study was to synthesis paramagnetic mesoporous silica from rice husk ash waste; knowing the characteristics of silica gel and mesoporous silica from rice husk and the value of adsorption capacity (Q). Based on the results of the study, it was found that mesoporous silica can be synthesized from the rice husk ash waste. Characterization using FTIR produces silanol (Si-OH), and siloxan (Si-O-Si). The use of 30% w/w tartaric acid as a template doesn’t change the functional groups of silica. The optimum conditions of adsorption of pinostrobin compounds by mesoporous silica at the adsorption capacity of 7.049 mg/g. In simulated intestinal fluids (pH 7.4),pinostrobin is released slowly at every hour, then slightly increases at the 10th hour and continues to increase again slowly so that the pinostrobin compound is completely released at 12 hours.