Development of Novel Eubiotic Drug Formulations and a Process for their Manufacturing
Tech Area / Field
- MED-DRG/Drug Discovery/Medicine
- BIO-IND/Industrial Biotechnology/Biotechnology
8 Project completed
Senior Project Manager
Weaver L M
State Research Center of Virology and Biotechnology VECTOR / Institute of Aerobiology, Russia, Novosibirsk reg., Koltsovo
- US Department of Defense / Defense Threat Reduction Agency, USA, VA, Fort Belvoir
Project summaryThe treatment of dysbacteriosis, a widespread disorder among the population of Russia, requires an application of special drugs — eubiotics (such as Bifidumbacterin, Lactobacterin, Colibacterin, Bificol, Bifilong, etc.), that bring the function of gastrointestinal tract back to normal. Due to the present high occurrence of this disease, the real need for eubiotic drugs is estimated as about 40 blns. doses in a year, whereas the existing national production capacity does not exceed 450 bil. doses annually. In order to fill this dramatic gap, the Russian Ministry of Healthcare outlined a package of measures, among them are: the improvement of current production technologies; the expansion of production capacities; and, the most important, the development and launch of novel eubiotic formulations possessing an increased therapeutic efficiency.
A particular feature of eubiotics is that that they contain alive cultures of bacteria comprising normal healthy inhabitance of a human gastrointestinal tract, and a clue to the therapeutic value of an eubiotic formulation is the viability of bacteria it contains. Modern trends in the design of eubiotics are, firstly, the creation of complex drugs containing several species of bifido- and lactobacteria in one formulation, and, secondly, the development of encapsulated and/or immobilized composite drugs with prolonged terms of storage at ambient temperatures. Because of apparent medical and economical benefits, these new types of eubiotic drugs draw considerable attention not only in CIS countries (Russia, Ukraine, Belarus, and Kazakhstan), but also in Japan, USA and Germany.
The clinical and laboratory experience shows that an eubiotic drug looses more than 90% of its initial activity before it reaches the intestines, on the way through the stomach. We believe that the viability of an active component and, hence, the therapeutic efficiency of the whole formulation can be markedly enhanced by means of immobilization of alive bacterial cells on porous microcarriers. At IOA extensive studies are now under way on composite formulations prepared by the immobilization of one of the most active strain, B. bifidum No. 791, on the porous microcarrier SUMS. SUMS is a fine powder of aluminium oxide (40-100 mcm) used in medicine as an effective enterosorbent. Compared with other types of enterosorbents (zeolites, microcrystalline cellulose, active charcoal), SUMS has the highest specific surface area and does not affect the K/Na ionic balance in gastrointestinal tract. Physico-chemical and toxicological studies of the composite formulations are now in progress, preclinical trial are expected to be performed at SRC VB "Vector" in the nearest future.
The main objective of the proposed project is the creation of a new composite eubiotic formulation on basis of the immobilized Bifidumbacterin, as well as a new complex formulation containing the most active strains of several species of bifidobacteria and acidophilic bacteria. This includes the physico-chemical study of the formulations, the evaluation of their antagonistic activity, preclinical trials on laboratory animals and, finally, clinical trials on volunteers. Together with experimental studies, an appropriate technological documentation (Pilot Manufacturing Regulations, technological directions), quality control regulations (Provisional Pharmacopea Article) and application manual have to be elaborated. The results of experimental studies, the set of documentation and samples from pilot series of the new eubiotic drugs will be presented at Tarasevitch GISK to perform state acceptance trials. At the final stage of the project we expect to launch a pilot scale facility for the manufacturing of the new eubiotic drugs.
In accordance with the stated above, we propose a project "Development of novel eubiotic drug formulations and a process for their manufacturing".
Following tasks will be accomplished in the course of the project fulfillment:
1. Design of novel and efficient immobilized and complex eubiotic formulations and the manufacturing of their experimental samples.
2. Experimental studies and process development for the production of new drugs (including the process for growing and harvesting of bifido- and lactobacteria, and methods of accelerated freeze drying and spray drying).
3. Physico-chemical and microbiological study of the formulations and evaluation of their antagonistic activity towards standard cultures of pathogenic microbial species.
4. Preclinical trials of the formulations on laboratory animals, assessment of their clinical properties and toxicological safety, selection of the most efficient formulations.
5. Clinical trials of the selected formulations on volunteers. Elaboration of the application manual on the basis of the trials.
6. Development of required documentation in accordance with existing regulations; presentation of the complete set of documentation and samples from pilot series of the new eubiotic drugs at Tarasevitch GISK to perform state acceptance trials.
7. Adjustment of the production process and facilities and beginning of the pilot scale manufacturing of the new eubiotic drugs.