Taste Masking of Orodispersible Films: A Case Study in Palatability Optimization

It’s all about the taste when David Tisi from Senopsys writes an article and we are happy to share his view on “Taste Masking of Orodispesible Films” with you in this article.

Orodispersible films (ODFs) are strips of water-soluble polymer matrices which contain an active ingredient that dissolves or disintegrates on contact with saliva. ODFs can be formulated for lingual, sublingual or buccal delivery, offering opportunities for local or systemic absorption. Although some oral films are formulated to adhere to the oral mucosa (“mucoadhesive”) enabling sustained release at the application site, most are non-mucoadhesive and are formulated to dissolve or disintegrate rapidly in the oral cavity without the need for water or chewing.

ODFs offer a convenient alternative to traditional solid oral dosage forms, particularly the ability to take the medicine without water; an advantage shared with orally disintegrating tablets (ODTs). This product attribute makes taking medicine easy and discrete. It can also help ensure successful administration for patients who have difficulty swallowing tablets and capsules (dysphagia) or (“institutionalized”) patients who refuse administration by “cheeking” and expectorating tablets and capsules.

Disadvantages of ODFs are a relatively low drug loading owing to their traditional postage stamp size and thickness, and sensitivity to temperature and humidity necessitating specialized manufacturing and packaging. It should be noted that some ODT technologies also share these limitations.

Formulating for Function and Palatability

ODFs incorporate excipients that provide essential functional properties:

Film Formers – natural or synthetic hydrophilic (water soluble) polymers that form the film matrix and account for 40-50% of the total composition.
Plasticizers – used to improve the flexibility and reduce the brittleness of the films (i.e., mechanical properties).
Processing Aids – used to solubilize the drug active and improve viscosity of the film precursor solution/suspension.
Saliva Stimulating Agents – organic acids produce sourness which promotes salivation providing the fluid necessary to breakdown the film.
Disintegrants – hydrophilic materials that “wick” saliva and help break down the film in the oral cavity.

In addition to creating the necessary form and functional properties of oral films, palatability is critical to patient acceptance recognizing that many drug actives are bitter, burning or malodorous¹.

For some drug actives, application of a barrier coating may be required to “sequester” the drug active from the taste receptors. Challenges for this approach include drug loading limitations of ODFs and the requirement for small sized particles to avoid the perception of grittiness, generally less than 100 microns².

Barrier coatings are rarely 100% effective for taste masking and may negatively affect bioavailability. By applying techniques from the food industry, “flavor systems” may be formulated to reduce residual taste effects of the drug active and film matrix. The composition of a typical flavor system includes high intensity sweeteners, buffers, taste modifiers and identifying aromatics (e.g., citrus, berry, mint). The flavor system may also include Saliva Stimulating Agents, such as organic acids which produce sourness to promote salivation providing additional fluid to breakdown the film more quickly.

Sensory-Directed Approach

This case study demonstrates how quantitative sensory analysis can guide the development of palatable, patient-accepted ODFs. Four ODF prototypes (2 x 2 design of two sweetener systems and two flavor types) and a commercial ODT were evaluated using the Flavor Profile Method (an ASTM / ISO analytical sensory methodology). The results were then analyzed using Senopsys’ FlavorMetrics℠ Palatability Profile.

Patient acceptability of a drug product is a function of both its initial flavor and aftertaste. The FlavorMetrics℠ Palatability Profile maps a product’s initial flavor quality as measured by Amplitude (balance and fullness) against its aftertaste flavor quality as measured by the degree of coverage of the aversive attribute (bitterness). Empirical decision boundaries relate measured flavor quality to patient palatability and expected compliance:

Green: Palatable with good prospects for acceptance and adherence.
Yellow: Sub-optimal, requiring further optimization
Red: Unpalatable (likely to be rejected) potentially requiring a different taste-masking strategy

Results and Discussion

The FlavorMetrics℠ Palatability Profile (see figure below) revealed that optimizing the sweetener system significantly improved the overall flavor quality of the prototype ODFs, surpassing even the commercial ODT. While the initial and aftertaste flavor quality were similar between the Citrus and Berry flavored ODFs, the optimized sweetener system #2 significantly improved palatability.

This is not a surprising result as taste and smell represent completely different modalities, just like the sense of sight is different than touch. The perception of bitterness is mitigated by balancing with the complementary basic tastes – sweet, sour and salty. The optimized sweetener system effectively reduced bitterness, and further improvements may be possible through additional adjustments to the sweetener system or increased sourness.

FlavorMetrics℠ Palatability Profile

Conclusions

Palatability is a critical factor in medication acceptance and adherence. The choice of taste-masking technology depends on the severity of the drug’s aversive sensory attributes (taste, aroma, mouthfeel, and texture). This study demonstrates the value of sensory analysis by trained panels, using standardized quantitative methods in conjunction with the FlavorMetrics℠ Palatability Profile, to guide the development of palatable and effective taste-masked oral dosage forms.

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Author: David Tisi, Senopsys LLC

Senopsys LLC is a specialty services firm dedicated to the development of palatable drug products. Senopsys uses GCP-compliant taste assessment tools to identify the taste attributes of APIs and drug products and measure the flavor quality of drug product prototypes. The company’s formulation scientists are experienced in the art and science of taste masking and develop palatable liquid, powder and solid dosage forms of investigational and approved drugs for pediatrics and adults.

¹ TISI, David A.; WORTHINGTON, Jeffrey H. Taste Masking Challenge of 155 Active Pharmaceutical Ingredients. Medical Research Archives, [S.l.], v. 12, n. 10, oct. 2024. ISSN 2375-1924. Available at:<https://esmed.org/MRA/mra/article/view/5890>. doi: https://doi.org/10.18103/mra.v12i10.5890.

²Engelen L, van der Bilt A, Schipper M, Bosman F. Oral size perception of particles: effect of size, type, viscosity and method. J Texture Stud. 2005;36:373–86. https://doi.org/10.1111/j.1745-4603.2005.00022.x.