Palatable Levocetirizine Dihydrochloride Solid Dispersed Fast-Dissolving Films: Formulation and In Vitro and In Vivo Characterization

Abstract

One of the most important issues for bitter-tasting drugs such as levocetirizine dihydrochloride (LCD) is the production of palatable dosage forms. LCD also has a delayed onset of action following oral administration. In this study, solid dispersed fast-dissolving films (FDFs) of LCD using the solvent casting method for oral application were prepared and evaluated. The FDF is composed of HPMC as the film forming polymer and different types of superdisintegrants (sodium starch glycolate, croscarmellose sodium, or crospovidone). FDF containing crospovidone showed the highest percentage release of the drug (100.54% ± 1.47 within 3 min.) and was chosen for fabricating into palatable solid dispersed FDFs using different ratios of gelatine. The results of Raman and FTIR revealed that the drug’s crystalline structure has been disrupted, and the drug has intermolecular hydrogen bonds with gelatine. The solid dispersed FDF (LF-7), which contained the drug in the form of a 1 : 1 solid dispersion with gelatine, showed a rapid in vitro disintegration (25 seconds) and a burst release of the drug (99.22% ± 2.22 within one min). The in vivo studies were conducted on human participants and showed a significant ( p < 0.05 ) reduction in disintegration time (9.43 ± 2.16 sec.) and higher taste masking ability of the solid dispersed FDF (LF-7) compared to the nonsolid dispersed FDF (LF-4). The stability studies indicated that the prepared FDF remained stable over three months. Overall, FDFs of levocetirizine dihydrochloride with a palatable and rapid onset of action were developed to relieve allergic symptoms.

The Potential of Films as Transmucosal Drug Delivery Systems

“…Based on a brief analysis of these studies, the most cited polymers were HPMC, polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), and sodium alginate (SA), while in relation to production methods, solvent casting was the most used technique. Finally, the health conditions mentioned were: (a) hypertension [69][70][71][72][73][74][75], (b) psychological disorders [76][77][78][79][80], (c) migraine [61,[81][82][83][84][85], (d) allergic conditions [85][86][87][88][89][90], (e) vomiting and nausea [91,92], (f) diabetes [60,93,94], (g) menopausal symptoms [95,96], (h) erectile dysfunction [97], (i) tuberculosis [98], (j) Alzheimer's [99], (k) smoking [59], (l) heart failure [100], (m) epilepsy [82], (n) HIV [101], and (o) sedation [102]. Below, we describe examples of recently published studies that were successful in the development of buccal films.…”

“…In a study by Al-Kubati et al [90], the authors aimed to develop solid, dispersed, fastdissolving films (FDFs) of levocetirizine dihydrochloride by using gelatine as a dispersing agent for LCD and hydroxypropyl methylcellulose as a film-forming agent, with the purpose of treating the symptoms of allergic conditions. Oral fast-dissolving films are formulations composed of hydrophilic polymers that quickly dissolve or disperse when in contact with the oral mucosa.…”