Low-Substituted Hydroxyproxyl Cellulose

Chemical properties

Low-substituted hydroxypropyl cellulose occurs as a white to yellowish white powder or granules. It is odorless or has a slight, characteristic odor, and it is tasteless.

Production Methods

Low-substituted hydroxypropyl cellulose is manufactured by reacting alkaline cellulose with propylene oxide at elevated temperature. Following the reaction, the product is recrystallized by neutralization, washed, and milled.

Pharmaceutical Applications

Low-substituted hydroxypropyl cellulose is widely used in oral solid-dosage forms. It is primarily used as a disintegrant, and as a binder for tablets and granules in wet or dry granulation. It has been used in the preparation of rapidly disintegrating tablets produced by direct compression methods.In addition, lowsubstituted hydroxypropyl cellulose has been used as a binder/ disintegrant included in the powder layering process on spherical cores and to prepare pellets by extrusion/spheronization. A low particle size and high hydroxypropyl content is recommended to produce round spheres and rapid dissolution.
There are a number of grades that have different particle sizes and substitution levels. LH-11 has the longest fibrous particles, and is typically used as an anticapping agent and disintegrant for direct compression. LH-21 is less fibrous and is used as a binder and disintegrant for tablets through the wet-granulation process. LH-31 is a small-particle grade used especially for extrusion to produce granules, as it has a small particle size that is better for passing a screen. LH-B1 is the nonfibrous, high-density grade designed for fluid-bed granulation, and can be used for direct compression and/ or formulations with a high low-substituted hydroxypropyl cellulose loading. Lower substitution grades LH-22 and LH-32 can be used for better disintegration capability, depending on the characteristics of the active ingredients.
The typical content of low-substituted hydroxypropyl cellulose in a formulation is approximately 5–50%.

Safety

Low-substituted hydroxypropyl cellulose is generally regarded as a nontoxic and nonirritant material.
Animal toxicity studies showed no adverse effects in rats fed orally 6 g/kg/day over 6 months. No teratogenic effects were noted in rabbits and rats fed 5 g/kg/day.
LD50 (rat, oral): >15 g/kg

Storage

Low-substituted hydroxypropyl cellulose is a stable, though hygroscopic, material. The powder should be stored in a wellclosed container.

Incompatibilities

Alkaline substances may interact. If a tablet formulation contains such a material, the disintegration time may be extended after storage.

Regulatory Status

Included in the FDA Inactive Ingredients Database (oral capsules, tablets, pellets). Approved for use in pharmaceuticals in Europe, Japan, USA, and other countries. Included in the Canadian List of Acceptable Non-medicinal Ingredients.