Optimal protection of stabilised dry live bacteria from bile toxicity in oral dosage forms by bile acid adsorbent resins

We previously found that dried live bacteria of a vaccine strain can be temporarily sensitive to bile acids and suggested that Bile Adsorbing Resins (BAR) can be used in oral vaccine tablets to protect dried bacteria from intestinal bile. Here, we report a quantitative analysis of the ability of BAR to exclude the dye bromophenol blue from penetrating into matrix tablets and also sections of hard capsule shells. Based on this quantitative analysis, we made a fully optimised formulation, comprising 25% w/w of cholestyramine in Vcaps™ HPMC capsules. This gave effectively 100% protection of viability from 4% bile, with 4200-fold more live bacteria recovered from this formulation compared to unprotected dry bacteria. From the image analysis, we found that the filler material or compaction force used had no measurable effect on dye exclusion but did affect the rate of tablet hydration. Increasing the mass fraction of BAR gave more exclusion of dye up to 25% w/w, after which a plateau was reached and no further dye exclusion was seen. More effective dye exclusion was seen with smaller particle sizes (i.e. cholestyramine) and when the BAR was thoroughly dried and disaggregated. Similar results were found when imaging dye penetration into capsule sections or tablets. The predictions of the dye penetration study were tested using capsules filled with dried attenuated Salmonella vaccine plus different BAR types, and the expected protection from bile was found, validating the imaging study. Surprisingly, depending on the capsule shell material, some protection was given by the capsule alone without adding BAR, with Vcaps™ HPMC capsules providing up to 174-fold protection against 1% bile; faster releasing Vcaps Plus™ HPMC capsules and Coni Snap™ gelatin capsules gave less protection.

Protection of live bacteria from bile acid toxicity using bile acid adsorbing resins

We previously demonstrated that a dry, room temperature stable formulation of a live bacterial vaccine was highly susceptible to bile, and suggested that this will lead to significant loss of viability of any live bacterial formulation released into the intestine using an enteric coating or capsule. We found that bile and acid tolerance is very rapidly recovered after rehydration with buffer or water, raising the possibility that rehydration in the absence of bile prior to release into the intestine might solve the problem of bile toxicity to dried cells. We describe here a novel formulation that combines extensively studied bile acid adsorbent resins with the dried bacteria, to temporarily adsorb bile acids and allow rehydration and recovery of bile resistance of bacteria in the intestine before release. Tablets containing the bile acid adsorbent cholestyramine release 250-fold more live bacteria when dissolved in a bile solution, compared to control tablets without cholestyramine or with a control resin that does not bind bile acids. We propose that a simple enteric coated oral dosage form containing bile acid adsorbent resins will allow improved live bacterial delivery to the intestine via the oral route, a major step towards room temperature stable, easily administered and distributed vaccine pills and other bacterial therapeutics

The EU, counter-terrorism and the protection of Muslims as European minorities

This article examines the EU’s promotion of the religious identity of Muslims within the context of European counter-terrorism measures. Counter-terrorism laws of the EU and its Member States impact on the religious identity of Muslims. They have an arguably disproportionate effect on the civil rights of individuals in the quest to combat terrorism and can be seen to increase Islamophobia in two ways: a rise in general discrimination against Muslims and a requirement on Muslims to distance their connection to Islamic practice and traditions. EU law dealing with terrorist offences speak little of this backlash that Muslims face in European countries. Although the EU has somewhat of a framework in place which concerns the protection of Islamic identity, the reluctance of the EU to take a determined stance on the issue of the protection of religious identity is illustrated through the ambiguous nature of its legislation.

Wanted dead and alive : to what extent are hunting and protection of an endangered species compatible?

Cash-constrained wildlife departments must increasingly look towards revenue-generating activities such as sales of permits for hunting common species combined with fines for those caught with rare species. Pertinent to west Africa, an optimal enforcement model demonstrates the conditions under which a department with neither external budget nor tourism revenue can fully protect a rare species, and the impact on other species and local hunters' livelihoods. The department's effectiveness is shown to depend critically on the extent to which hunters can discriminate among different species. Improvements in hunting technology selectivity are therefore a substitute for increased enforcement spending.