Product Description

Chewable tablets as a dosage form are growing in popularity, and the potential for this drug delivery system is expanding. Though drug delivery by chewable tablet would be highly advantageous in many cases, usage has been limited as formulators have encountered difficulties in achieving satisfactory sensory characteristics.

Avicel CE-15 incorporates particle-engineered products and process technology allowing the formulator to overcome the old barriers and bring new ideas to market.

FMC BioPolymer developed Avicel CE-15 in response to industry-wide needs and specific customer requests, driven by a number of market factors.

• In the pediatric market, there is strong demand for dosage forms that can be chewed rather than swallowed.
• The shift towards more over-the-counter medications makes it more difficult for physicians and pharmacists to influence patient compliance. Palatable chewable tablets encourage compliance.
• Chewable OTC tablets are also desirable because they offer convenience for consumers.
• Doses can be minimized through chewable tablets.

Applications

Controlled Sensory Characteristics
Avicel CE-15 provides excellent control of sensory factors that affect palatability. Smoother mouthfeel can be attained. Grittiness can be eliminated. Toothpacking can be significantly reduced. An overall texture can be modified so the resulting chewable dose form yields a creamy feeling dispersion.

Improvement in Perceived Taste
The most challenging problem in chewable tablet development is taste masking. Many active ingredients have a very bitter or otherwise unpleasant taste that conventional masking techniques cannot overcome. Avicel CE-15 imparts such pleasing sensory features to chewable tablets that the perceived taste of drugs is remarkably altered.

Greater Palatability Means Better Compliance
The true test of Avicel CE-15 is in the mouth of the patient. By helping to make a chewable tablet that has a pleasant taste and mouthfeel, Avicel CE-15 may have a direct, positive impact on patient compliance.

Other Practical Advantages
As one of the world's leading suppliers of functional excipients for pharmaceutical applications, FMC BioPolymer understands the importance of facilitating drug manufacturing and distribution. Avicel CE-15 is, therefore, designed to perform in direct compression formulations, producing comparably softer tablets that are less friable and disintegrate rapidly. Avicel CE-15 processes well upon scale-up and is compatible with conventional formulation excipients.

Benefits

The superior organoleptic performance of Avicel CE-15 in chewable tablets results in dramatic differences for end users, primarily in the areas of overall sensory experience and perceived taste, when compared to existing products.

When chewing a tablet formulated with Avicel CE-15, the user experiences:

• Less grittiness
• Reduced tooth packing
• Minimal chalkiness
• Creamier mouthfeel
• Improved overall palatability

The FMC BioPolymer Solution: Particle Engineering and Processing Technology
As the manufacturer of a wide range of Avicel microcrystalline cellulose products, FMC BioPolymer is highly skilled at using innovative processing technology to achieve new MCC functionalities. Our co-processed mixtures of MCC and sodium carboxymethylcellulose, Avicel RC/CL products, illustrate this point.

Combining this knowledge of processing technology with particle engineering skills, FMC BioPolymer has met the chewable tablet challenge with Avicel CE-15 - a patented combination of MCC and guar gum that imparts unprecedented sensory characteristics.

Sensory Performance Data
Throughout the product development and testing process, during which manufacturing feasibility and verification were demonstrated, sensory characteristics were monitored carefully.

Trained sensory panels involving 30 people were used to evaluate chewable dosage forms in the course of developing Avicel CE-15. These individuals were all specially trained by the National Food Laboratory.

A variety of active drugs were tested in chewable forms, with panelists characterizing physical, flavor and textural properties. The organoleptic properties, summarized below, led to the validation of a number of products in chewable dosage forms.

Detailed Product Information

Microcrystalline cellulose and guar gum are generally recognized as safe (GRAS) by qualified experts. Guar gum is listed under 21 CFR 184.1339. Avicel CE-15 is manufactured in accordance with current Good Manufacturing Practices, and are in compliance with the Federal Food, Drug and Cosmetic Act, as amended, and applicable regulations. FMC BioPolymer maintains a Drug Master File at the U.S. Food and Drug Administration to support the use of Avicel CE-15 in drug products.

Additional regulatory information for Avicel CE-15 is available upon request.

Guidelines for Use Levels and Typical Formulations
Avicel CE-15 has been shown to be effective at low ranges in several cases. In practice, however, use levels of Avicel CE-15 will be dependent upon many factors specific to the product being developed. Key among them will be the type and level of active ingredient, the dose level per tablet, overall formulation objectives, and other excipients used in the formulation. The choice of polyols is a critical factor, especially when their cooling effect and influence on sweetness are considered. Avicel CE-15 will make a desirable impact on your specific formulation, whether it is a new product or reformulation.

New Products
The performance properties of Avicel CE-15 suggest that the preferred development approach is to begin with the active and Avicel CE-15 in a range up to 10%. This is followed by addition and optimization of types and levels of polyols, especially xylitol and mannitol, leading to the most significant sensory enhancement and processing benefits. Using these excipients can result in cost-effective new products with exceptional sensory performance.

Product Reformulations
Incorporating Avicel CE-15 into a reformulation of an existing product can dramatically improve sensory characteristics. Though this can often be achieved by simply adding Avicel CE-15 to an existing product, replacing varying levels of other excipients with Avicel CE-15 can be particularly beneficial in improving performance.

Case History Summaries
FMC BioPolymer has formulated Avicel CE-15 into several products demonstrating its wide effective use range with a variety of actives. The following summaries of several OTC product reformulations illustrate sensory and process benefits.

Product	Problem	FMC BioPolymer Approach	Results
Adult Chewable Acetaminophen Tablet	Gritty, chalky mouthfeel	Add 10% Avicel CE-15 in place of like amount of mannitol	Improved overall mouthfeel; less grittiness, chalkiness, toothpacking; perceived better taste
Adult Chewable Antacid Tablet	Extreme hardness (22Kp), high friability (1.5%)	Add 9% Avicel CE-15 extragranular	More acceptable hardness (9Kp) and reduced friability (0.5%)
Adult Chewable Aspirin Tablet	Gritty mouthfeel, chalky residue	Add 10% Avicel CE-15 in place of like amount of mannitol	Creamier, less gritty texture; low toothpacking; decreased friability; better compressibility at scale-up
Large Chewable Antacid Tablet	Large 2 gram size, poor mouthfeel, high friability	Add 3% Avicel CE-15, allowing for removal of 0.7 grams of other excipients (40% reduction in excipients usage)	Smaller tablet; improved mouthfeel; friability reduced from 1.25% to 0.9%
Chewable Antacid Tablet	Poor overall mouthfeel	Add 2% Avicel CE-15 in place of like amount of mannitol	Overall sensory performance improved

Regulatory Status of Avicel CE-15
Microcrystalline cellulose and guar gum are generally recognized as safe (GRAS) by qualified experts. Guar gum is listed under 21 CFR 184.1339. Avicel CE-15 is manufactured in accordance with current Good Manufacturing Practices, and are in compliance with the Federal Food, Drug and Cosmetic Act, as amended, and applicable regulations. FMC BioPolymer maintains a Drug Master File at the U.S. Food and Drug Administration to support the use of Avicel CE-15 in drug products.

Additional regulatory information for Avicel CE-15 is available upon request.

Shelf Life/Storage Conditions for Avicel® CE-15
Store Avicel CE-15 at ambient conditions in sealed containers, as the material is very hygroscopic. If storage conditions are observed, there is no expiration date.

Production Sites
Avicel CE-15 is manufactured at FMC BioPolymer's plant in Newark, DE

Kosher Status
Avicel CE-15 is certified as Kosher. For certificates, please contact your nearest representative.

Product Brochure

For a copy of a product brochure, please click here.

Application Bulletin

For a copy of an application bulletin on CE-15 please click here.

MSDS

For a copy of the MSDS, please click here.