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
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.
||Relative Rate of Hydration
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.