Fabrication of oral acid resistant Fermosorb (ferment+sorbent)-type preparations can be simplified using industrial Bacillus subtilis culture filtrates as an enzyme source

Abstract

In our recent article [Biziulevičius, G.A. and Žukait≐, V., 1999. Int. J. Pharm. 189, 43–55] we described a novel approach in design of oral preparations intented for intestinal delivery of enzymes, based on reversible immobilization of the latter onto the polymer matrix. Fermosorb (ferment+sorbent)-type preparations, produced in such a way, are characterized as two-component delayed-release enzyme formulations being stable at acidic pH and thus ensuring the protection of an active substance in the environment of the gastric region and liberating the active substance through dissociation of the enzyme–polymer complex at neutral pH values characteristic for the intestines. In the present paper we report our updated findings showing that the technology of fabrication of two Fermosorb-type preparations manufactured (namely Fermosorb and Polyferm) can be simplified (as well as their production cost reduced) substituting the acetone precipitated enzyme preparation solutions, currently used as an enzyme source, by their precursors — industrial Bacillus subtilis culture filtrates. Moreover, we give a description of how one more Fermosorb-type preparation aimed at intestinal delivery of amylolytic enzymes can be produced in a similar manner. Determination of immobilization conditions has revealed, that irrespectively of the enzyme origin (lytic, proteolytic or amylolytic) and its source (1% acetone precipitated preparation solution or culture filtrate), optimal for immobilization v/w ratio of the liquid phase and the polymer matrix (Biocarb L) remains the same and is equal to 10:1 (approximate). The main differences have been found to be in optimal for immobilization pH values as well as process duration in regard to the two enzyme sources applied. In case of proteolytic and amylolytic enzymes only one of the variables was different (process duration for the first ones, optimal pH for the second ones), while in case of lytic enzymes both variables were different. The percentage of the enzymes activity uptaken from the reaction mixture formed by either of the enzyme sources and the polymer matrix (≈60%) as well as activity losses at drying the enzyme–polymer complexes (≈20%), tolling in the final activity yield of near 40%, were found to be very similar.