ヒプロメロースフタル酸エステル 化学特性,用途語,生産方法
効能
コーティング剤
化学的特性
White to off-white free-flowing flakes or granules
調製方法
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.
応用例（製薬）
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.
安全性
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.
貯蔵
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.
不和合性
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.
規制状況(Regulatory Status)
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.
ヒプロメロースフタル酸エステル 上流と下流の製品情報
原材料
準備製品