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

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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.

Pharmaceutical Technology
Volume 33, Issue 2, pp. 48-56

The RDFs containing 200 mg HPMC E15 LV formulated with CTZ resulted in films with good quality and acceptable in vitro disintegration time (45 s). Films with 400 mg HPMC E15 LV resulted in higher in vitro disintegration time (95 s), which might be a result of delayed disintegration time with the higher viscosity grade of HPMC E LV.

Incorporating CTZ with 200 mg of HPMC E3 LV resulted in the formation of very brittle and thin films. CTZ incorporated with 400 mg of HPMC E3 LV resulted in slightly brittle films. Thus, it is necessary to add placticizer to improve the characteristics of these films. Various preliminary formulations (E1 to E8) using 400 mg of HPMC E3 LV were prepared with glycerol and menthol as plasticizers to evaluate film separation. None of these batches exhibited good film separation. Batches were prepared with glycerol and PEG 400. The batch with PEG 400 at a plasticizer:polymer ratio of 0.2:1 exhibited better elasticity than the batch prepared with glycerol. Therefore, film separation could be improved in the presence of plasticizer.

The in vitro disintegration time of batch E9 containing 400 mg of HPMC E3 LV, CTZ, and PEG 400 was 25 s. The comparative drug release of batch E9 in various dissolution media indicated 85% drug release in 2 min in distilled water, 81% drug release in 2 min in 0.1 N HCl, and 78% drug release in 2 min in simulated saliva.

Therefore, the viscosity grades of HPMC E LV affected the mechanical properties, disintegration, and dissolution characteristics of the RDFs. Higher viscosities of HPMC E LV grade exhibited increased in vitro disintegration and dissolution times. Although batches containing 400 mg HPMC E5 LV and 200 mg HPMC E15 LV in presence of drug had an in vitro disintegration time of 45 s, the in vitro dissolution time was 30 min and 45 min in distilled water, respectively. Batch E9 had 85% drug release in 2 min in distilled water. RDFs containing CTZ prepared with HPMC E3 LV also possessed satisfactory mechanical properties, in vitro disintegration, and in vitro dissolution time and were used for further optimization. Therefore, further trials were carried out using HPMC E3 LV as the polymer for RDF formulation development.

Taste masking of CTZ films. Because CTZ is bitter in taste, taste masking the films was essential to improve patient acceptability. To improve the taste of the films, flavors and sweeteners were incorporated in the film formulation.

The addition of menthol (5% w/w of drug and polymer amount) and aspartame (10% w/w of drug and polymer amount) at various plasticizer ratios did not mask the taste of the film. Thus, further trial batches S1 to S4 were taken with the sweetener sucralose, which also did not result in taste masking of the films. Additional trials were conducted using combinations of aspartame and sucralose.

Table III : Selection of flavors.
Table II shows that films of batch S4 had a satisfactory in vitro disintegration time of 50 s. In vivo disintegration time of the film of batch S4 was 20 s. This batch possessed a good taste masking property but also had a bitter aftertaste. Thus, further formulation modifications were carried out by adding flavoring agents such as lemon and passion fruit flavors and sour ingredients such as citric acid.


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