Process for the preparation of pharmaceutical microcapsules with enhanced taste-masking and high dissolution rate

Abstract

Process for the production of microcapsules containing a drug and comprising a layer of ethylcellulose and a layer of an acrylic polymer and microcapsules produced thereby.

Description

FIELD OF THE INVENTION [0001] The present invention relates to the field of microencapsulation of active principles. A new process is described allowing to obtain pharmaceutical microcapsules with enhanced taste masking and an optimal dissolution profile. STATE OF THE ART [0002] Achieving an effective encapsulation of active principles is important for the preparation of a variety of compositions; when microparticles of an active principle must be singly provided with an external coating, microencapsulation techniques are employed. [0003] The microencapsulation process consists in coating small drug cores (microparticles) with a layer of polymer. The polymer layering may be achieved by different techniques; in particular the microencapsulation by phase separation (or coacervation), proved very reliable in obtaining coated microparticles (M. Calanchi, “Taste Masking of oral formulations”, Pharmaceutical Manufacturing International, pp. 139-141, 1996; L. Dobetti, S. De Luigi, “Develop...

AI Technical Summary

Benefits of technology

[0011] The present application discloses a microencapsulation process characterised by coating drug cores with a first layer of ethylcellulose and further coating the obtained microcapsules with a layer of an acrylic polymer. The obtained microcapsules show a high potency, an optimal taste masking, and ensure a quick release in the stomach. The invention allows thus to produce superior pharmaceutical formulations, especially useful in the case of drugs with unpleasant taste in particular drugs, which require an immediate delivery in the stomach, even if the administration in form of reconstitutable suspensions is required.

Problems solved by technology

As a consequence, it is easy to prepare taste-masked, slow-release microcapsules, whereas it is more difficult to obtain taste-masked quick-release ones: the latter form is nevertheless very desired, in particular for those drugs with unpleasant taste which, for pharmacokinetic and pharmacodynamic reasons, must be delivered quickly in the stomach: one typical example is that of antibiotic drugs (for example Penicillins, Cephalosporins, Carbapenem, Penems, Penams, Aminoglycosides, Macrolides, Ketolides, Tetracyclines, Quinolones, etc.) which are often endowed with an unacceptable taste: they require a strong taste-masking, but at the same time they must be delivered and absorbed quickly in the stomach, so to ensure a quick onset of action and avoid disturbing the intestinal bacterial flora.

However ethylcellulose-coated microparticles are not capable to associate, to the good taste masking, an elevated dissolution rate in the stomach.

In order to overcome this problem, attempts have been made to reduce the thickness of the microcapsule wall (i.e. using less encapsulating polymer); however this is not a good solution because the taste-masking is no longer ensured by the thinner coating.

The use of coating polymers alternative to ethylcellulose, having e.g. higher solubility in the stomach is equally unsatisfactory: in fact, these polymers require much a thicker coating to achieve the same level of taste masking of ethylcellulose; as a result microcapsules with very low potency are obtained: they require bulky dosage forms such as large tablets or capsules, thus quite problematic from the point of view of patient acceptability.

In addition, with respect to ethylcellulose, polymers with higher solubility present problems of particle aggregation during the coating process, with the result that small-size singly coated microparticles are yet more difficult to obtain.

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