Ignorance is Bliss in Solid Dosage Taste-Masking

April 10, 2013
Cynthia A. Challener
Cynthia A. Challener

Cynthia A. Challener is a contributing editor to Pharmaceutical Technology.

The trick to taste-masking in solid dosage forms is to never let the taste buds have a chance.

Although taste-masking is more often associated with pediatric and geriatric liquid formulations, the APIs used in solid dosage drugs often have a very bitter flavor as well. Tablets and capsules are swallowed whole, thus masking the taste of the ingredients involves prevention of dissolution before the pill reaches the stomach. Nigel Langley, head of technical sales for pharma ingredients and services at BASF Pharma Ingredients and Services, discussed the two approaches to taste-masking of solid and semisolid dosage drugs with Cynthia Challener, editor of the Pharmaceutical Sciences, Manufacturing and Marketplace Report.

Choice of protection
Pharmaceutical Sciences, Manufacturing and Marketplace Report:
What are different methods that can be used to achieve a taste-masking effect for solid and semisolid dosage forms?

Langley (BASF): There are two approaches to taste-masking of solid and semisolid drugs, and both involve coating the product in some way with a polymer. The goal of the coating is to prevent disintegration and release of the drug into the mouth or throat so the taste buds are never exposed to the API. In one method, a sustained-release polymer system is used, and in the other, an instant-release polymer that exhibits pH-dependent solubility ensures that the drug remains whole until swallowed. These polymer coatings can be applied to the entire tablet or capsule, or to crystals, granules, or other particulates used to manufacture the final dosage form.

API characteristics are importantPharmaceutical Sciences, Manufacturing and Marketplace Report: What factors must be considered when selecting a taste-masking excipient for a particular API/formulated drug?

Langley (BASF): APIs themselves can be acidic. Most polymers that have pH-dependent solubility characteristics are basic. Therefore, the choice of polymeric coating type can be influenced by the nature of the API. It is, however, possible to apply a barrier coating to the tablet or particle before the pH-dependent coating is applied if this type of taste-masking system is preferred.

The chemistry mattersPharmaceutical Sciences, Manufacturing and Marketplace Report: What is the chemistry of the different types of taste-masking polymers? How does each type generally work?

Langley (BASF): Our [BASF] pH-dependent polymer is based on acrylate chemistry and is an aqueous dispersion of a copolymer comprised of methyl methacrylate and diethylaminoethyl methacrylate. This coating is stable at neutral pH, and thus does not dissolve in saliva, which generally has a pH of 6.8-7.2. Below pH 5.5, however, the polymer will form salts. Thus, in the stomach, where the pH is typically 1.2, but can be a little higher in people who suffer from acid reflux, the coating reacts with biosalts, becomes soluble, and the drug is released. In fact, the coating operates in the opposite manner to an enteric coating.

Sustained-release coatings work because they can be formulated with both water- insoluble and water-soluble polymers, the latter of which is referred to as a pore former. The sustained release behavior of the coating can be tuned by varying the amount of pore former and therefore customized to meet the release profile required for a specific solid dosage drug.

Different polymer types have been used as sustained release coatings, including cellulose-based resins. BASF’s polyvinylacetate water-insoluble film former is offered as a 30% dispersion in water. Our water-soluble pore former is a polyvinyl alcohol-polyethylene glycol graft copolymer with polyethylene glycol (PEG) units incorporated into the backbone that impart flexibility.

New technologies improve performancePharmaceutical Sciences, Manufacturing and Marketplace Report: What specific new technology has BASF developed and how is it an improvement over current products? What might be expected in the future?

Langley (BASF): The instant-release technology from BASF is unique in that, even though the acrylate copolymer is basic, it has a very bland odor. At least one other pH-dependent taste-masking product on the market smells strongly of ammonia, which is quite offensive in the manufacturing setting. In addition, BASF’s polymer hides very bitter tastes at a reduced coating thickness compared to other products on the market. It also prevents moisture uptake, which is an added benefit for sensitive solid dosage formulations. Furthermore, because it is a dispersion in water, no organic solvent is required for spraying of the coating.

These advantages, in fact, led Colorcon to recognize our acrylate technology as the best-in-class reverse enteric polymer for taste-masking, according to general manager for film coating Kamlesh Oza. As a result, BASF and Colorcon have been in a collaboration since October, 2011 for the development of film-coating systems using BASF’s polymer. Colorcon has developed a preformulated additive system for use with the BASF coating that lowers the number of materials to be dispensed by 50% and reduces the preparation time by almost 40%, thus enabling efficient preparation and application for taste-masking of solid and semisolid dosage forms.

The pH-dependent technology was introduced two years ago and has attracted a lot of interest. It takes quite some time for pharmaceutical customers to adopt a new excipient and get a product approved by the FDA, but we are working closely with our customers to reach that goal.