Formulation Development of Taste-Masked Rapidly Dissolving Films of Cetirizine Hydrochloride

The authors formulated and developed taste-masked RDFs of cetirizine hydrochloride for patients who experience difficultly in swallowing the tablet dosage form of the drug.
Feb 02, 2009
Volume 33, Issue 2

Rapidly dissolving dosage forms have acquired great importance in the pharmaceutical industry because of their unique properties (1, 2). Rapidly dissolving dosage forms are also called quick-dissolving delivery systems; quick-disintegrating, orally disintegrating, mouth dissolve dosage forms; or melt-in-mouth dosage forms (1, 3, 4). In less than one minute, these dosage forms disintegrate or dissolve in the salivary fluids of the oral cavity, releasing the drug and inactive ingredients. Most of the drug is swallowed with the saliva where subsequent absorption takes place in the gastrointestinal tract (3, 4).

Rapidly dissolving dosage forms offer advantages such as disintegration without water, rapid onset of action, ease of transportability, ease of handling, pleasant taste, and improved patient compliance. These dosage forms are most widely available as rapidly dissolving tablets (3, 4). Lyophilized wafers, thin strips, and films are newer types of rapidly dissolving dosage forms that can be manufactured using technologies such as freeze drying, vacuum drying, the incorporation of superdisintegrants, spray drying, and molding methods (1, 2).

Rapidly dissolving films (RDF) have been popular in the market predominantly for breath-freshening products. However, RDFs have recently been introduced in the United States and Europe for therapeutic products as well (2, 5–8). A film or strip comprises a water soluble polymer that causes the film or strip to dissolve when placed on the tongue. The first oral strip was developed by Pfizer (New York) as a mouth freshening product ("Listerine" pocket packs). "Chloraseptic Relief Strips" (distributed by Prestige Brands, Irvington, NY), for the treatment of sore throat pain, was the first therapeutic oral thin-film product that contained benzocaine (6, 8).

RDFs are prepared using fast disintegrating polymers that possess good film-forming properties e.g., hydroxypropyl methylcellulose [HPMC], pullulan, and hydroxypropylcellulose [HPC]) (9). HPMC E LV is a low-viscosity white to off-white modified cellulose powder that is a good solubilizer and possesses swelling characteristics. Various grades of HPMC E LV (i.e., E3, E5, and E15) were selected for this study. Solvent casting, semisolid casting, hot melt extrusion, solid dispersion extrusion, and rolling are processes used to manufacture RDFs. Solvent casting is the most common and traditional method (2). RDFs are typically evaluated for thickness, mechanical properties such as tensile strength and elasticity, in vitro and in vivo disintegration, and in vitro dissolution (10, 11).

Cetirizine hydrochloride (CTZ) is an orally active and selective H1-receptor antagonist used to treat seasonal allergic rhinitis, perennial allergic rhinitis, and chronic urticaria. CTZ is a white, crystalline water-soluble drug with a bitter taste (12, 13). Because of sore throat conditions, patients may experience difficulty in swallowing a tablet. Therefore, an RDF would serve as an ideal dosage form for these patients.

The authors formulated and developed an RDF of CTZ. The study of a CTZ RDF also involved applying taste-masking techniques to formulate a dosage form with acceptable taste. HPMC with various viscosity grades (i.e., E3, E5 and E15 LV) was selected as the film-forming polymer, and solvent casting was selected as a method of manufacture.

Materials and methods

Table I : In vitro disintegration time of preliminary batches without drug.
Materials. Cetirizine hydrochloride was received as a gift sample from Troikaa Pharmaceuticals (Ahmedabad, India). HPMC E3 LV, HPMC E5 LV, and HPMC E15 LV were received as gift samples from Colorcon Asia (Goa, India). Sucralose was obtained as a gift sample from Alkem Lab (Ankleshwar, India). Citric acid anhydrous was purchased from Central Drug House (New Delhi, India). Menthol and polyethylene glycol (PEG) 400 were purchased from S.D. Fine Chem (Mumbai, India). Aspartame was purchased from Hi-Media Lab (Mumbai). Passion fruit flavor and lemon flavor were received as gift samples from Pentagon Trading Company (Ahmedabad, India). All other chemicals were of analytical grade and were used without further purification. Double distilled water was used for the study.

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