Controlled Release Capsules

Hydroxypropylmethylcellulose, or Methocel, is a cellulose derivative polymer that is used as a hydrophilic matrix material. When Methocel hydrates, it forms a gel of such consistency that drug diffusion through the gel can be controlled. A hydrophilic matrix controlled release system is a dynamic system composed of polymer wetting, polymer hydration, and polymer dissolution. At the same time, other soluble excipients or drugs will also wet, dissolve, and diffuse out of the matrix while insoluble materials will be held in place until the surrounding polymer erodes or dissolves away.

Initially, the surface becomes wet and Methocel polymer starts to partially hydrate forming a gel layer on the surface of the capsule. As water continues to permeate into the capsule, the gel layer becomes thicker, and soluble drug will diffuse out through the gel layer. Ultimately, water will dissolve the capsule shell and continue to penetrate into the drug core. So release is controlled by the dissolution of soluble drug into the penetrating water and diffusion across the gel layer.

To formulate a successful hydrophilic matrix system, the polymer substance must wet and hydrate to form a gel layer fast enough to protect the interior of the capsule from dissolving and disintegrating during the initial wetting and hydration phase. If the polymer is too slow to hydrate, gastric fluids may penetrate to the capsule core, dissolve the drug substance, and allow the drug to diffuse out prematurely. Even among the family of hydroxypropylmethylcellulose products (Methocel E, F, and K), there are significant differences in the rate at which the polymers will hydrate. This is due to the varying proportions of the two chemical substituents attached to the cellulose backbone, hydroxypropoxyl and methoxyl substitution.

• The methoxyl substituent is a relatively hydrophobic component and does not contribute as greatly to the hydrophilic nature of the polymer and the rate at which it will hydrate.
• The hydroxpropoxyl group does contribute greatly to the rate of polymer hydration.

As a result, Methocel K products are the fastest to hydrate because they have the lower amount of the hydrophobic methoxyl substitution and a higher amount of the hydrophilic hydroxypropoxyl substitution. The range of chemical substitution in Methocel products is shown below.

Increasing the concentration of the polymer in a matrix system increases the viscosity of the gel that forms on the capsule surface. Therefore, an increase in the concentration of the polymer used will generally yield a decrease in drug diffusion and drug release. An increase in the concentration of polymer also tends to put more polymer on the capsule surface. Wetting is more readily achieved so gel formation is accelerated.