Orodispersible Films with Rupatadine Fumarate Enclosed in Ethylcellulose Microparticles as Drug Delivery Platform with Taste-Masking Effect

Abstract

Orally disintegrating (orodispersible) films provide a versatile tool for drug administration, especially in the pediatric and geriatric population, since they reduce the risk of choking and do not necessitate drinking water during application. By considering their direct contact with the taste buds, palatability is an influential aspect related to patient compliance. The microparticles based on taste-masking polymers containing drugs enclosed inside effectively mask the unpleasant taste of medicines. Ethylcellulose is a hydrophobic polymer widely used as a taste-masking material. Rupatadine fumarate, a second-generation antihistamine drug, is characterised by an intense bitter taste; therefore, it is crucial to achieve a tolerable taste whilst developing orodispersible formulations with its content. The objective of this study was to develop orally disintegrating films with rupatadine fumarate in the form of ethylcellulose-based microparticles obtained from aqueous dispersions of ethylcellulose—Surelease® or Aquacoat® ECD. It was a technological challenge to achieve homogenous drug content per dosage unit and sufficient mechanical properties for film operating due to the necessity to suspend the microparticles in the casting solution. Although the process of obtaining films consisted of several steps (mixing, pouring, drying), the particles were homogeneously dispersed, and each film of the desired size contained the proper dose of the drug. The taste-masking effect was also maintained. This parameter was confirmed by three independent methods: in vivo by healthy volunteers, an electronic tongue and a dissolution test. The applied taste-evaluation techniques showed that the films containing Aquacoat® ECD microparticles have the highest degree of bitter taste reduction, which confirms the results obtained in our previous studies.

Incorporation of Ethylcellulose Microparticles Containing a Model Drug with a Bitter Taste into Nanofibrous Mats by the Electrospinning Technique—Preliminary Studies

“…The taste masking effect of the obtained formulations was determined in vivo by a human taste panel and in vitro by a drug dissolution test. The formulation prepared with MP-A-RUP (F3) was rated as non-bitter to slightly bitter ( Table 2 ) compared to the formulation containing pure RUP (F2), which is in agreement with our previous results [ 26 , 30 ]. In the dissolution test, it was shown that formulation F2 released RUP very fast, whereas F3 was characterised by a much slower drug release ( Figure 3 ).…”

“…Mats were tested in terms of tensile strength—TS, Young’s modulus—E, the percent of elongation at break—EB, and tear resistance—TR by a texture analyser (TA.XT plus, Stable Micro Systems, Godalming, UK). A piece of mat was placed in the bracket at a height of 20 mm and then extended with a 1 mm/s speed and a 5 kg cell loading [ 30 ]. Each study was performed at least in triplicate.…”

“…The evaluation of the taste-masking efficacy of the obtained nanofibrous mats was performed in vivo, involving six healthy volunteers [ 30 ] (Approval of Bioethics Commission number APK.002.112.2021). Briefly, after the mouth was rinsed with purified water, the mat was held in the mouth for 30 s and spat out, and then the mouth was rinsed again.…”

Orodispersible Films—Current State of the Art, Limitations, Advances and Future Perspectives

“…A similar approach was used by Marzouk and co-workers [ 76 ] where the complexation of fluoxetine with β-cyclodextrins led to a taste-masking effect and also by Khan et al who focused on the developing of ODF with cefixime trihydrate and β -CD inclusion complexes [ 10 ]. Another example of manufacturing ODF with successful masking of the API bitter taste is the study of Olechno and co-workers [ 23 , 77 ]. An orally disintegrating film was developed with rupatadine fumarate in the form of ethylcellulose-based microparticles, using the solvent-casting method and electrospinning.…”

“…Improving the bioavailability of some APIs was a trigger for implementing solutions that enable controlling the rate of drug release. In this way, ODFs became a carrier for microparticles [ 23 ], nanoparticles [ 24 ], or nanocrystals [ 18 ], and self-emulsifying systems [ 25 ]. The development is also visible in another aspects, namely in manufacturing methods.…”