Gastroresistant Pharmaceutical Formulations Containing Rifaximin

Abstract

The object of the invention consists of pharmaceutical formulations containing rifaximin in the shape of microgranules made gastroresistant by an insoluble polymer at pH values between 1.5 and 4.0 and soluble at pH values between 5.0 and 7.5, by their preparation and by their use in the manufacture of medicinal preparations useful in the treatment of inflammatory bowel diseases (IBD) and mainly Crohn's disease.

Description

[0001]This application is a continuation under 35 U.S.C. §120 of U.S. patent application Ser. No. 11 / 814,628, filed Jul. 24, 2007, which is a 35 U.S.C. §371 national phase filing of PCT Application No. PCT / EP2006 / 002022, filed Mar. 6, 2006, which claims priority to Italian Application No. BO 2005 A 000123, filed Mar. 7, 2005, the contents of each of which are hereby incorporated by reference.[0002]The object of the invention consists of pharmaceutical formulations containing rifaximin in the shape of microgranules made gastroresistant by an insoluble polymer at pH values between 1.5 and 4.0 and soluble at pH values between 5.0 and 7.5, by their preparation and by their use in the manufacture of medicinal preparations useful in the treatment of inflammatory bowel diseases (IBD) and mainly Crohn's disease.BACKGROUND OF THE INVENTION[0003]The intestinal apparatus is affected by many inflammatory diseases generally capped as inflammatory bowel diseases. In particular, Crohn's disease is...

AI Technical Summary

Benefits of technology

The gastroresistant rifaximin microgranules effectively target the intestinal tract, reducing side effects and improving patient compliance with long-term therapy by maintaining high drug concentration and bioavailability, enhancing treatment efficacy for inflammatory bowel diseases.

Problems solved by technology

The high systemic bioavailability of these antibiotics is at the root of their high incidence of side effects registered in long-term therapies, which negatively impacts their use.

Moreover, the low absorption profile of rifaximin reduces the incidence of side effects and the unwanted risk of pharmacological interactions.

However, the absence of a placebo group in the clinical trial does not allow to draw confident conclusions, see Rizzello, Gut., 2000, 47, Supp.

However, the suggested posology the use of the rifaximin 200 mg tablets has to be considered sub optimal due to the need up to six tablets a day for three months, resulting in a poor patient compliance.

Thus, when the rifaximin finally reaches the intestinal tract, the concentration is too low resulting in the need for increasing dosages.

In such condition it is very difficult using conventional systems like fluid bed coating or pan technology.

If present, one or both of these aspects would have negative impact in any further medicinal preparation.

Indeed, several drawbacks could occur without any powder pre-treatment such as large clamp formation, large range of particle diameter, inhomogeneous composition of microgranules, no uniform coating layer.

The occurrence of some of these drawbacks is common with rifaximin, the powder of which is composed by a fine particles, and is extremely hydrophobic, electrostatic, hygroscopic and difficult to be mixed with common excipients in powder.

Moreover it has a predisposition to segregate not allowing homogenous mixture.

In presence of such unfavourable characteristics to get coated rifaximin would required the use of more than one step and a large quantity of excipients, which would limit the pharmaceutical strengths of human dosage.

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