Taste-masking assessment of orally disintegrating tablets and lyophilisates with cetirizine dihydrochloride microparticles

Abstract

Orally disintegrating tablets and oral lyophilisates are novel attractive dosage forms that disintegrate or dissolve in the buccal cavity within seconds without necessity of drinking. The major limitation in designing of these dosage forms is unpleasant taste of the drug substance. Cetirizine dihydrochloride is a H₁-antihistamine substance indicated for the treatment of allergy. It is characterized by extremely bitter taste, therefore in order to deliver cetirizine dihydrochloride using orodispersible formulations, effective taste-masking is required. The aim of this study was to investigate whether microparticles containing cetirizine dihydrochloride could be successfully used to formulate orally disintegrating tablets by direct compression method and oral lyophilisates by freeze-drying process. Taste masking of cetirizine dihydrochloride was achieved by the spray-drying technique using Eudragit^® E PO as the drug agent carrier. Based on the preliminary studies, optimal compositions of microparticles, tablets and lyophilisates were chosen. Obtained dosage forms were characterized for drug content, disintegration time and mechanical properties. In order to determine whether the microparticles subjected to direct compression and freeze-drying process effectively mask the bitter taste of cetirizine dihydrochloride, the in vivo and in vitro evaluation was performed. The results showed that designed formulates with microparticles containing cetirizine dihydrochloride were characterized by appropriate mechanical properties, uniformity of weight and thickness, short disintegration time, and the uniform content of the drug substance. Taste-masking assessment performed by three independent methods (e-tongue evaluation, human test panel and the in vitro drug release) revealed that microparticles with Eudragit^® E PO are effective taste - masking carriers of cetirizine dihydrochloride and might be used to formulate orally disintegrating tablets and oral lyophilisates.

Keywords: Cetirizine dihydrochloride; E-tongue; Oral lyophilisates; Orally disintegrating tablets; Taste masking.

Fig. 1

SEM image of tablet obtained by direct compression using 7.2 kN tensile force (x 10 000; arrow indicates cracked surface of microparticle).

Fig. 2

SEM images of unprocessed microparticles with CET (a) x 10000, (b) x 20000, orally disintegrating tablet (formulation T6) obtained by direct compression method using 3.7 kN tensile force (c) and oral lyophilisate (d) x 20000 (arrows indicate microparticles in the tablet or lyophilisate matrix).

Fig. 3

In vitro CET release from unprocessed taste-masked microparticles used as a control, orally disintegrating tablets (formulation T6) and oral lyophilisates in phosphate buffer (pH 6.8).

Fig. 4

Two dimensional principal component analysis score plots of chemical images of CET formulations (description of samples according to Table 3).