Фталат гидроксипропилметилцеллюлозы

Химические свойства

White to off-white free-flowing flakes or granules

Методы производства

Hypromellose phthalate is prepared by the esterification of hypromellose with phthalic anhydride. The degree of alkyloxy and carboxybenzoyl substitution determines the properties of the polymer and in particular the pH at which it dissolves in aqueous media.

Фармацевтические приложения

Hypromellose phthalate is widely used in oral pharmaceutical formulations as an enteric coating material for tablets or granules. Hypromellose phthalate is insoluble in gastric fluid but will swell and dissolve rapidly in the upper intestine. Generally, concentrations of 5–10% of hypromellose phthalate are employed with the material being dissolved in either a dichloromethane : ethanol (50 : 50) or an ethanol : water (80 : 20) solvent mixture. Hypromellose phthalate can normally be applied to tablets and granules without the addition of a plasticizer or other film formers, using established coating techniques. However, the addition of a small amount of plasticizer or water can avoid film cracking problems; many commonly used plasticizers, such as diacetin, triacetin, diethyl and dibutyl phthalate, castor oil, acetyl monoglyceride, and polyethylene glycols, are compatible with hypromellose phthalate. Tablets coated with hypromellose phthalate disintegrate more rapidly than tablets coated with cellulose acetate phthalate.
Hypromellose phthalate can be applied to tablet surfaces using a dispersion of the micronized hypromellose phthalate powder in an aqueous dispersion of a suitable plasticizer such as triacetin, triethyl citrate, or diethyl tartrate together with a wetting agent.
Hypromellose phthalate may be used alone or in combination with other soluble or insoluble binders in the preparation of granules with sustained drug-release properties; the release rate is pH-dependent. Since hypromellose phthalate is tasteless and insoluble in saliva, it can also be used as a coating to mask the unpleasant taste of some tablet formulations. Hypromellose phthalate has also been co-precipitated with a poorly soluble drug to improve dissolution characteristics.

Безопасность

Hypromellose phthalate is widely used, primarily as an enteric coating agent, in oral pharmaceutical formulations. Chronic and acute animal feeding studies on several different species have shown no evidence of teratogenicity or toxicity associated with hypromellose phthalate.Hypromellose phthalate is generally regarded as a nonirritant and nontoxic material.

хранилище

Hypromellose phthalate is chemically and physically stable at ambient temperature for at least 3–4 years and for 2–3 months at 40°C and 75% relative humidity. It is stable on exposure to UV light for up to 3 months at 25°C and 70% relative humidity. Drums stored in a cool, dry place should be brought to room temperature before opening to prevent condensation of moisture on inside surfaces. After 10 days at 60°C and 100% relative humidity, 8–9% of carbyoxybenzoyl group were hydrolyzed. In general, hypromellose phthalate is more stable than cellulose acetate phthalate. At ambient storage conditions, hypromellose phthalate is not susceptible to microbial attack.

Несовместимости

Incompatible with strong oxidizing agents.
Splitting of film coatings has been reported rarely, most notably with coated tablets that contain microcrystalline cellulose and calcium carboxymethyl cellulose. Film splitting has also occurred when a mixture of acetone : propan-2-ol or dichloromethane : propan- 2-ol has been used as the coating solvent, or when coatings have been applied in conditions of low temperature and humidity. However, film splitting may be avoided by careful selection of formulation composition, including solvent, by use of a higher molecular weight grade of polymer, or by suitable selection of plasticizer.
The addition of more than about 10% titanium dioxide to a coating solution of hypromellose phthalate, which is used to produce a colored film coating, may result in coating with decreased elasticity and resistance to gastric fluid.

Регуляторный статус

Included in the FDA Inactive Ingredients Database (oral capsules and tablets). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.