Cetirizine is a second-generation antihistamine drug, which is used for relieving nose and eye symptoms of seasonal or perennial allergic rhinitis as well as for relieving symptoms of chronical idiopathic urticaria due to its antiallergic properties. There are mostly solid dosage forms available on the market, which are however, in terms of application, less appropriate for children and people with difficulty swallowing. With the purpose of enhancing patient compliance and improving therapeutic outcomes, we wanted to prepare a more suitable dosage form – straws filled with granulation containing cetirizine.
After reviewing the literature and performing analyses on the active ingredient in the preformulation phase, we formed the process of granulate production. In the process, besides the appropriate dissolution rate of the active ingredient and performance of the granulate in the straw, the amount of granulate was important as well, because 5 mg dose for children and 10 mg dose for adults was too small for filling in the straw and we had to increase the quantity. Firstly, we layered neutral pellets with cetirizine chloride and after that, we added film layer of polymer for masking the unpleasant substance taste. We tested five following polymers and combinations of polymers: poly(vinil alcohol) (PVOH 28-29), poly(ethyl acrylate-co-methyl methacrylate-co-trimethylammonioethyl methacrylate chloride) (Eudragit® RL 30 D) alone and in combination with poly(ethyl acrylate-co-methyl methacrylate-co-trimethylammonioethyl methacrylate chloride) (Eudragit® RS 30 D), polyvinyl acetate (Kollicoat® SR 30 D) and poly(ethyl acrylate-co-methyl methacrylate) (Eudragit® NE 30 D). The pellets were then granulated with sugars and sugar alcohols (mannitol, trehalose, isomalt, erythritol, xylitol, sorbitol, maltitol, sucrose), which formed an additional layer around the pellet cores.
Through every stage of the process, we regulated comparison of results by standardizing particle size and evaluating products in every stage. After layering the pellets, we particularly evaluated release of the drug, which needs to be fast for rapid onset of therapeutic effects. For granulates, pressure in the straw during the sipping simulation was crucial. Among the produced granules, those prepared with xylitol and erythritol gave best results. This finding corresponds with results of dissolution rate of sugar alcohols. Polyols that dissolved faster produced lower pressures. We also established interesting correlation between difficulty of granulation process and its successfulness. Polyols, with which granulation process was easier, formed more even layers around coated pellet cores, what we evaluated with optic microscope.
Based on dissolution results, we concluded that all of the studied pellet coats are appropriate. Based on the obtained results and from a financial point of view, erythritol is the most appropriate choice for granulation excipient. For further experiments it would be wise to prepare granulates with erythritol with all five coated pellets and test them in a straw. Furthermore, analysis of taste masking would be wise. Formulation with the best results in a straw and the best taste masking properties would be the most appropriate in terms of the wanted properties of the final product.
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