Artful Taste Masking Improves Patient Compliance

Lipids have found extensive use as functional excipients in taste masking because:

• They control drug release in the oral cavity, preventing buildup of a concentration higher than the bitterness threshold;
• They have a biocompatible nature, which increases their acceptability in the human body
• They can alter pharmacokinetics of APIs by modulating release profiles; and
• They have low melting points, ideal for incorporating drugs in methods like hot-melt extrusion, melt granulation, spray drying, and emulsification.

Selecting a lipid depends on its physiochemical properties and the desired quality of the dosage form. Lipid membrane taste sensors have been widely used in assessing taste and palatability of pharmaceutical formulations using electronic tongue (e-tongue).²

Complexation is especially applicable for liquid products (e.g. cyclodextrins, ion exchange resins). The purpose of the complexing agent is to mask the unpleasant taste of specific drug either by reducing its oral solubility or reducing the amount of the drug particles interacting with taste buds. One of the most popular approaches in the masking of the taste of bitter drugs is based on ion exchange resin complexes (IER). IER are the polyelectrolytes of the high molecular weight of solids, and, in a suitable insoluble form, can exchange their ions in movement the load equal to the surrounding medium.³ According to webinar, IER enables more flexible formulation of a bitter API. Generally, a weak cation or anion exchange resin is used for taste masking purposes so that the loosely bound drug is released in the gastrointestinal tract.

With complexation, IERs binds or exchange ions with the polymer, but does not necessarily engulf the molecule. With inclusion complexation, on the other hand, there is hydrophobic interaction between the API and the donut shaped cyclodextrin, which acts as the host and engulfs the API to prevent its exposure to the bulk solution. The complexing agent masks the bitter taste of the drug by either decreasing its oral solubility upon ingestion or decreasing the amount of drug particles exposed to taste buds, thereby reducing the perception of bitter taste. This method is most suitable for low dose drugs.⁴

A coating or granulation prevents interaction of the harsh tasting medicine by blocking the drug contact with the taste buds in mouth. These taste maskers offer a physical wall around the medicine, and can be applied using:

• Spray drying: Spray drying converts a feed from a fluid state – emulsion, suspension or solution – into dried particulate form by subjecting the feed to a hot drying medium. Dried particles are separated and collected in the form of microspheres in which the bitter drug is encapsulated/entrapped in a polymeric matrix. The spray-dried microspheres does not allow the drug to be released at salivary pH thus masking the bitterness in oral cavity. However, active drug is then rapidly released afterwards in gastric fluids. Thus, the taste is masked without interfering with the release of drug in gastric environment, which makes spray drying a suitable technique for taste masking immediate-release oral dosage forms.⁵
• Fluid Bed Granulation: A fluidized bed processor (agglomeration) is among highly efficient and simple methods of masking drug taste in formulations pediatric, tablets chewable, and liquid formulations liquid. The method involves fluidizing fine powders up to 50μm in expansion chambers through fast-moving hot air.⁶ Drug particles gush from the top of the expansion chamber with a spray nozzle and get covered with the coating solution on their way to the bottom. The coated granules are then dried in hot air.
• High Shear Granulation: This method turns powders into dense granules and thereby reduces the effective surface area. Granulation with polymer solution that prevent quick release in the saliva can reduce the exposure of the API and improve the taste perception of the oral granules or tablet formulation. Alternatively, for extremely bitter drugs, the dried granules can be coated in fluid bed with various polymers of choice to mask the taste and tailor the release profile of the formulation.
• Hot-melt Granulation: Pharmaceutical powders are efficiently agglomerated by the use of a low melting point binder, generally wax or lipid-based, which is added to the other components of the powder. At molten state, the binder acts as a granulating liquid and coats the drug to mask the taste.

Masking the bitter taste of the drug using multiple emulsions technique is also a good approach. This technique is achieved by dissolving the active pharmaceutical ingredient in the inner aqueous phase of w/o/w emulsion. The internal aqueous phase and the external aqueous phase are separated by the oil phase. Another type is o/w/o emulsion, in which water globules contain oil globules. The effectiveness of masking the bitter taste using both types of multiple emulsions is high.⁸

No matter the taste masking method chosen, a skilled contract development and manufacturing organization (CDMO) will take the following into account as they formulate the ideal taste masker for an API³:

• Minimal equipment and processing steps;
• Dosage delivery options (solution vs. suspension vs. granules/tablet)
• No effect to the bioavailability of the drug;
• Fewer excipients are needed to get the best formulation;
• Affordable raw materials;
• Reduced production costs; and
• Quick and easy preparation.

Most importantly, keep in mind that the appropriate choice of masking substance completely hides, anesthetizes, or changes the flavor of the sour tasting drug without altering the delivery mechanism of the drug. It is important to partner with an experienced CDMO that has the masking methods, uses state-of-the-art technology, and understands the art and science of taste masking.

1. Flavor Masking Agents Market to Hit $332.16 Million, Globally, by 2028 at 5.7% CAGR, The Insight Partners, April 4, 2022.
2. Lipids for Taste masking and Taste assessment in pharmaceutical formulations, Surojit Banerjee, et. al., ScienceDirect, Vol. 235, March 2021.
3. Taste Masking Practices in Sold form Drugs, Bushra Iftikhar, Rizwan Liaqat, Research and Reviews: Journal of Chemistry, Sept. 16, 2021.
4. Taste Masking Technologies in Oral Pharmaceuticals: Recent Developments and Approaches, Harmik Sohi, et. al., Drug Development and Industrial Pharmacy, Vol. 30, May 25, 2004.
5. Taste masking of bitter pharmaceuticals by spray drying technique, Deepak Kaushik and Harish Dureja, Journal of Chemical and Pharmaceutical Research, 2015.
6. Taste Masking: A Review, H.B. Pagar, et. al., Research Journal of Pharmacy and Technology, Vol. 5, Issue 2, 2012.
7. A Comparison of Granules Produced by High-Shear and Fluidized-Bed Granulation Methods, Garrett Morin and Lauren Briens, AAPS PharmSciTech, Aug. 2014.
8. Taste Masking Approaches for Unpleasant Taste Drugs, Noora Abdulla AlAteibi and Aliasgar F. Shahiwala, Boffin Access, Oct. 21, 2019.