(M0930-08-54) Use of Granulation and E-Tongue for Taste-Masking of an Orally Disintegrating Tablet (ODT)

Purpose: Taste-masking is an essential process for development of solid oral dosage forms to overcome unpleasant taste of the active ingredient or excipients used in the formulation. Poor palatability can have a negative impact on patient compliance, especially in the case of pediatric and geriatric patients who may also have difficulty swallowing pills or tablets. Taste-masking not only improves the acceptability of the medication but also enhances therapeutic outcomes by ensuring a consistent dose intake by the patient. Coating of the active molecule is an effective way to achieve taste-masking with additional benefits of enhancing overall product stability. The latter is afforded by preventing degradation of the active ingredient due to exposure to external factors such as humidity, temperature and light. Therefore, taste-masking in developing oral dosage forms is important to improve patient compliance, augment therapeutic outcomes as well as improving product shelf life. In this study, an orally disintegrating tablet (ODT) was formulated using racecadotril, an active drug used in the treatment of diarrhea. Oral disintegration is important for fast delivery of the active and taste-masking is key as there is immediate disintegration of the tablet in the mouth cavity. The formulation was ideated using HyperStart^®, Formulation Service and included StarTab^®, Directly Compressible Starch, as a key excipient to improve mouth feel. Taste-masking was achieved through coating/granulation with Opadry^® EC, Ethylcellulose Organic Coating System and the efficiency of taste-masking was assessed though use of the E-Tongue technique.

Methods: Racecadotril was granulated in a VFC-LAB 1 Fluid Bed (Vector Corporation) using Opadry EC. Samples were taken at 8 and 12% weight gain for further evaluation. To avoid rupturing, the dry granules were not subjected to a milling step. The resulting granules were mixed with mannitol, StarTab, sweetener, flavoring and magnesium stearate and compressed using a Piccola BD-EU (Riva S.A.) tableting machine. The composition of ODT is described in Table 1. The inclusion or exclusion of a flavor enhancer, neohesperidin, was evaluated during the granulation process. Tablets were evaluated for weight, hardness, friability and disintegration time. Taste-masking was evaluated using E-Tongue (Impedance Analyzer - Solartron 1260). Either an ODT (350 mg) or the active drug (100 mg) was diluted in 10 mL of artificial saliva and a 20 µL sample is then placed at the tip of each electrode. Electrical impedance data of frequency range of 1 Hz - 1 MHz, applying 25 mV of voltage at 20ºC is measured. Methodology flow is shown in Figure 1.

Results: The ODTs exhibited acceptable mouth feel and good tablet characteristics, with average tablet hardness of 4-5 kp, friability of 0.3% and disintegration time of about 7 minutes. E-Tongue taste-masking results were conducted on 7 samples. Figure 2 shows the results of E-Tongue evaluation. These techniques are basically for pattern recognition of data. In the generated graphs, each impedance spectrum is represented by a point (symbol), and distant points mean that the spectra are quite different from each other. That is, the electrical properties of the samples under analysis are quite distinct when the corresponding data are placed apart on a PCA and HCA plot. It should be noted that in the analyses with electronic languages the hypothesis is adopted that a difference in electrical properties is correlated with difference in taste. Therefore, an electronic language is considered to mimic the biological flavor recognition system. The taste-masking results showed that samples 4 and 6 (granulation with 12% WG Opadry EC) are the most distinct in terms of electrical properties compared to API alone.

Conclusion: Excellent oral disintegration tablets (ODT) were developed based on the recommended HyperStart Formulation Service, saving time on initial formula design. Use of the starch-based excipient, StarTab, improved the mouth feel and disintegration times. This work showed that use of Opadry EC in granulation at 12% WG achieved excellent taste-masking and would deliver a positive experience for patients to improve compliance. The use of neohesperidin can improve mouth feel but is not critical for taste-masking.

References: 1. Efficient Praziquantel Encapsulation into Polymer Microcapsules and Taste Masking Evaluation Using an Electronic Tongue *jcarlosso@hotmail.com (J. C. Machado), fmshimizu@yahoo.com.br (F. M. Shimizu), nadia.volpato@ufrgs.br (N. M. Volpato) 2018
2. Guidance for Industry - Incorporation of Physical-Chemical Identifiers into Solid Oral Dosage Form Drug Products for Anticounterfeiting. https://www.fda.gov/downloads/drugs/guidances/ucm171575.pdf April 2019

Figure 1: E-Tongue Methodology

Table 1. Formulation of Orally Disintegrating Tablets (ODT)

Figure 2. Results obtained through E-Tongue