Immediate release pharmaceutical granule compositions and a continuous process for making them

Abstract

An immediate or fast release pharmaceutical granule composition comprising at least one drug (i) classifiable as Class II or Class IV of the Biopharmaceutical Classification System, wherein the said drug constitutes at least about 0.5% by weight and no more than 50% by weight of the composition, the said composition further comprising (ii) a first excipient being a dextrin-containing compound and a second excipient (iii) being selected from the group consisting of polyethylene glycols and polypropylene glycols having weight number molecular weights between about 300 and 10,000, glycerol, propylene glycol and glycerides.

Description

FIELD OF THE INVENTION The present invention is in the field of drug delivery systems and immediate release technology. Particularly, the invention is in the field of immediate or fast release pharmaceutical solid, preferably granule, compositions. More specifically, the invention relates to such compositions with low to moderate and even high drug loading for immediate or fast release of drugs which have low or very low solubility in water. The invention also relates to various solid pharmaceutical dosage forms such as sachets, gelules and tablets including such immediate or fast release pharmaceutical granule compositions. Still more specifically, the invention relates to immediate or fast release water-soluble granule veterinary compositions which can readily be administered to animals together with drinking water. Finally the invention relates to a continuous process for manufacturing said immediate or fast release pharmaceutical or veterinary granule compositions. BACKGROUND O...

AI Technical Summary

Benefits of technology

The present invention provides a way to formulate poorly soluble drugs into fast release pharmaceutical solid dosage forms. This is achieved by mixing the drugs with a combination of two acceptable excipients: a dextrin-containing compound or a blend of microcrystalline cellulose and a swellable polymer, and a non-aqueous wetting compound comprising at least a solid fraction. The resulting granule compositions can be used to make various pharmaceutical dosage forms such as sachets, tablets, and hard gelatin capsules. The invention also provides a method for treating bacterial infections in humans and animals by oral administration of the granule compositions.

Problems solved by technology

Tablets and capsules are generally unsuitable for administering high doses of biologically active ingredients since individual large dosage forms are difficult to swallow or necessitate the administration of several tablets or capsules at a time, leading to impaired patient compliance.

Thus, when a large amount of ingredient is required for each dosage unit, depending on the bulk density of the formulation, it may be necessary to use large size capsules which are too large to swallow or, even worse, a size 000 capsule may be too small to receive the said amount.

Pellets and granules have been filled into hard gelatin capsules to be used as conventional or controlled release dosage forms, however the latter are rather difficult to manufacture.

However, compaction of coated beads or pellets for making tablets encounters many difficulties and problems.

Another difficult problem is the formulation of drugs having low or very low water-solubility into solid dosage forms for immediate release.

Few solutions to this problem have been disclosed in the art.

This process suffers from the disadvantage of providing a heating zone in the twin screw extruder and consequently a need for controlling and monitoring the temperature profile of the extruder for efficient quality control.

However, none of the above processes appear to be successful in formulating solid dosage forms of drugs having very low water-solubility, i.e. a solubility lower than 10 μg / ml, preferably lower than 5 μg / ml.

A limitation of the technology disclosed in U.S. Pat. No. 6,368,634 is that it only allows to increase the dissolution rate of formulations containing a low content of active ingredient (i.e. drug loading) since the amount of liquid phase (solubilizer) that can be fixed onto the solid carrier particles is limited to a weight ratio solubilizer / particles from 1:5 to 1:2, and the active ingredient further needs to dissolve into the solubilizer.

Another limitation of the technology disclosed in U.S. Pat. No. 6,368,634 is thus that the stickiness of the wet mass formed in step (b) should not exceed a level where its extrusion in step (c) would become impossible and / or would block the extruder.

This proviso implies significant limitations on the liquid solubilizer that may be used according to U.S. Pat. No. 6,368,634.

In particular, the latter document does not teach or suggest the use of maltodextrins, and the skilled person knows that a mixture of water and a maltodextrin would have a stickiness much higher than permitted for extrusion.

Another limitation of this technology is the need for an energy-consuming drying step in the final stage of the extrusion-spheronisation process.

Until now the skilled person has failed in the design of such a solid formulation of florfenicol, which can further be admixed with animal feed if necessary.

Images