Hydroxypropyl Cellulose

Category

Binder Excipients

Grade

Pharmceutical Excipients

Description

Hydroxypropyl cellulose is a white to slightly yellow-colored, odorless and tasteless powder.

UNII

RFW2ET671P

Chemical Name

Cellulose, 2-hydroxypropyl ether

CAS Number

9004-64-2

Synonyms

Cellulose, hydroxypropyl ether; E463; hydroxypropylcellulosum; hyprolose; Klucel; Nisso HPC; oxypropylated cellulose.

Administration route

Oral; topical and transdermal

Dosage Form

Oral capsules and tablets; topical and transdermal preparations

Stability and Storage Conditions

Hydroxypropyl cellulose powder is a stable material, although it is hygroscopic after drying. Aqueous solutions of hydroxypropyl cellulose are stable at pH 6.0-8.0, with the viscosity of solutions being relatively unaffected.However, at low pH aqueous solutions may undergo acid hydrolysis, resulting in chain scission and hence a decrease in solution viscosity. The rate of hydrolysis increases with increasing temperature and hydrogen ion concentration.

Source and Preparation

A purified form of cellulose is reacted with sodium hydroxide to produce a swollen alkali cellulose that is chemically more reactive than untreated cellulose. The alkali cellulose is then reacted with propylene oxide at elevated temperature and pressure. The propylene oxide can be substituted on the cellulose through an ether linkage at the three reactive hydroxyls present on each anhydroglucose monomer unit of the cellulose chain. Etherification takes place in such a way that hydroxypropyl substituent groups contain almost entirely secondary hydroxyls. The secondary hydroxyl present in the side chain is available for further reaction with the propylene oxide, and ‘chaining-out’ may take place. This results in the formation of side chains containing more than 1 mole of combined propylene oxide.

Applications

Hydroxypropyl cellulose is widely used in oral and topical pharmaceutical formulations. In oral products, hydroxypropyl cellulose is primarily used in tableting as a binder, film-coating, and extended-release-matrix former.

Safety

Hydroxypropyl cellulose is widely used as an excipient in oral and topical pharmaceutical formulations. It is also used extensively in cosmetics and food products. Hydroxypropyl cellulose is generally regarded as an essentially nontoxic and nonirritant material. It is not absorbed from the gastrointestinal tract and is fully recovered in feces after oral administration in rats. It does not exhibit skin irritation or skin sensitization. However, the use of hydroxypropyl cellulose as a solid ocular insert has been associated with rare reports of discomfort or irritation, including hypersensitivity and edema of the eyelids. Adverse reactions to hydroxypropyl cellulose are rare. However, it has been reported that a single patient developed contact dermatitis due to hydroxypropyl cellulose in a transdermal estradiol patch. The WHO has specified an acceptable daily intake for hydroxypropyl cellulose of up to 1500 mg/kg body-weight.Excessive consumption of hydroxypropyl cellulose may have a laxative effect.
LD50 (rat, IV): 0.25 g/kg
LD50 (rat, oral): 10.2 g/kg

Incompatibilities

Hydroxypropyl cellulose in solution demonstrates some incompatibility with substituted phenol derivatives, such as methylparaben and propylparaben. The presence of anionic polymers may increase the viscosity of hydroxypropyl cellulose solutions. The compatibility of hydroxypropyl cellulose with inorganic salts varies depending upon the salt and its concentration. Hydroxypropyl cellulose may not tolerate high concentrations of other dissolved materials.The balance of the hydrophilic-lipophilic properties of the polymer, which are required for dual solubility, reduces its ability to hydrate with water and it therefore tends to be salted out in the presence of high concentrations of other dissolved materials. The precipitation temperature of hydroxypropyl cellulose is lower in the presence of relatively high concentrations of other dissolved materials that compete for the water in the system;