Micronized Ethylcellulose For Controlled Release Applications

The Dow Chemical Co. has released results from a recent study on micronized ehtylcellulose, which demonstrates the utility of a new form of the product, Ethocell Standard 10 FP Premium Ethycellulose (ESPE). In their investigation, Dow scientists Douglas Pollock and Karen Balwinski studied ESPE as a wet granulation aid in a model controlled release formulation. Their objective was to show that ESPE, when added to a formulation mix as a micronized powder, could deliver the same benefits as aqueous ethylcellulose without the limitations of the older formulation.

Ethocell Premium ethylcellulose ethers are a family of inert hydrophobic polymers that have been used as pharmaceutical vehicles since their commercial introduction in the mid-1930s. Ethylcellulose polymers are tasteless, odorless, colorless and noncaloric, and form strong, tough films at low concentrations. This unique combination of properties makes them useful in a variety of pharmaceutical applications. Ethylcellulose has been used as a taste masking coating material for tablets and granules, as a tablet binder, in the preparation of microcapsules and microspheres, and most importantly as a film/matrix forming material for controlled release formulations. Ethylcellulose is among only a very small number of water-insoluble excipient polymers that are approved and accepted globally for pharmaceutical applications.

Until recently, premium ethylcellulose polymers were only available in varying viscosity grades. The products were granular, with an average particle size greater than 250 µ. In the fall of 1995, Dow introduced a finely milled form of Ethocel, Ethocell FP Premium, which ranged in average particle size from a nominal 6 µ to 50 µ. These polymers are chemically equivalent to the existing standard ethoxyl grade of premium ethylcellulose materials and can be used in formulations without dissolution in organic solvents.

Methods

The basic test formulation used throughout the study was 16% acetaminophen and 84% lactose filler/ethylcellulose binder mix. The ethylcellulose was used at 1, 5, 10, and 20% levels with a corresponding reduction in the lactose content. Formulations were mixed for 10 minutes in a laboratory blender. In some formulations, triethyl citrate was added as a plasticizer.

Wet granulation of the dry formulation was conducted in a low shear planetary mixer. Granulation liquid was added via an atomizer to a final level of approximately 25%. The generated wet masses were dried overnight at 110° F, after which they were dry-milled.

Tablets were prepared on an automated laboratory press with 0.5-inch flat-faced tooling. Particle size distributions for crushed tablets were obtained using a sieve shaker; tablet thickness, hardness, and dissolution (in phosphate buffer at pH 7.0) were also tested (Figure 1).

Results

The results of this study are consistent with those in the literature that suggests that ethylcellulose, even though it is a water insoluble, can function as an aqueous granulation aid to improve the formation of granules, improve their compressibility and modify drug release. The micronized form of ethylcellulose, ETHOCEL Standard 10 FP, can be used to incorporate higher levels of polymer in a single granulation step than can aqueous dispersions of ethylcellulose, therefore simplifying the granulation process.

Specifically, the study authors found that:

• At constant amounts of water and granulation conditions, an increase in the weight percentage of micronized ethylcellulose in the dry mix resulted in products with lower levels of both product oversize and product fines.
• As the polymer level increases, the porosity of the tablet decreases, as measured by tablet thickness at constant tablet weight.
• When small levels of triethyl citrate were added, the granulations gave much softer tablets, although the plasticizer had no effect on the release rate of the drug (Figure 2).

For more information: Harold Nicoll, The Dow Chemical Co., 100 Larkin Center, Midland, MI 48674. Telephone: 517- 636-8068.