Name: Copovidone
CAS No: Acetic acid ethenyl ester, polymer with 1-ethenyl-2-pyrrolidinone [25086-89-9]
BP: Copovidone PhEur: Copovidone USP-NF: Copovidone
Acetic acid vinyl ester, polymer with 1-vinyl-2-pyrrolidinone; copolymer of 1-vinyl-2-pyrrolidone and vinyl acetate in a ratio of 3 : 2 by mass; copolyvidone; copovidonum; Kollidon VA 64; Luviskol VA; Plasdone S-630; poly(1-vinylpyrrolidone-co-vinyl acetate); polyvinylpyrrolidone-vinyl acetate copolymer; PVP/VA; PVP/VA copolymer.
Acetic acid ethenyl ester, polymer with 1-ethenyl-2-pyrrolidinone [25086-89-9]
(C6H9NO)n(C4H6O2)m (111.1)n þ (86.1)m The ratio of n to m is approximately n = 1.2m. Molecular weights of 45 000–70 000 have been determined for Kollidon VA 64. The average molecular weight of copovidone is usually expressed as a K-value. The K-value of Kollidon VA 64 is nominally 28, with a range of 25.2–30.8. The K-value of Plasdone S 630 is specified between 25.4 and 34.2. K-values are calculated from the kinematic viscosity of a 1% aqueous solution. Molecular weight can be calculated with the formula: M = 22.22 (K þ 0.075K 2 ) 1.65 The PhEur 6.0 and USP32–NF27 describe copovidone as a copolymer of 1-ethenylpyrrolidin-2-one and ethenyl acetate in the mass proportion of 3 : 2.
Copovidone is used as a tablet binder, a film-former, and as part of the matrix material used in controlled-release formulations. In tableting, copovidone can be used as a binder for direct compression(1–3) and as a binder in wet granulation.(4,5) Copovidone is often added to coating solutions as a film-forming agent. It provides good adhesion, elasticity, and hardness, and can be used as a moisture barrier
Copovidone is a white to yellowish-white amorphous powder. It is typically spray-dried with a relatively fine particle size. It has a slight odor and a faint taste
See Table II.
Density(bulk) 0.24–0.28 g/cm3 Density (tapped) 0.35–0.45 g/cm3 Flash point 2158C Flowability Relatively free-flowing powder. Glass transition temperature 1068C for Plasdone S-630. (6) Hygroscopicity At 50% relative humidity, copovidone gains less than 10% weight. K-value 25.4–34.2 for Plasdone S-630. (6) Melting point 1408C Solubility Greater than 10% solubility in 1,4-butanediol, glycerol, butanol, chloroform, dichloromethane, ethanol (95%), glycerol, methanol, polyethylene glycol 400, propan-2-ol, propanol, propylene glycol, and water. Less than 1% solubility in cyclohexane, diethyl ether, liquid paraffin, and pentane. Viscosity (dynamic) The viscosity of aqueous solutions depends on the molecular weight and the concentration. At concentrations less than 10%, the viscosity is less than 10 mPa
Copovidone is stable and should be stored in a well-closed container in a cool, dry place.
Copovidone is compatible with most organic and inorganic pharmaceutical ingredients. When exposed to high water levels, copovidone may form molecular adducts with some materials; see Crospovidone and Povidone
Copovidone is manufactured by free-radical polymerization of vinylpyrrolidone and vinyl acetate in a ratio of 6 : 4. The synthesis is conducted in an organic solvent owing to the insolubility of vinyl acetate in water.
Copovidone is used widely in pharmaceutical formulations and is generally regarded as nontoxic. However, it is moderately toxic by ingestion, producing gastric disturbances. It has no irritating or sensitizing effects on the skin. A study was conducted to look at the carcinogenicity and chronic toxicity of copovidone (Kollidon VA 64) in Wistar rats and Beagle dogs. The results of these studies demonstrated the absence of any significant toxicological findings of high dietary levels of copodivone in rats and dogs, resulting in noobserved-adverse-effect levels of 2800 mg/kg body-weight/day in rats and 2500 mg/kg body-weight/day in dogs, the highest doses tested.(7) LD50 (rat, oral): >0.63 g/kg(8)
Observe normal precautions appropriate to the circumstances and quantity of material handled. When heated to decomposition, copovidone emits toxic vapors of NOx. Eye protection, gloves, and a dust mask are recommended.
Copovidone is included in the FDA Inactive Ingredients Database (oral tablets, oral film-coated tablets, sustained action)
Crospovidone; povidone.
Copovidone is one of the materials that have been selected for harmonization by the Pharmacopeial Discussion Group. For further information see the General Information Chapter <1196> in the USP32–NF27, the General Chapter 5.8 in PhEur 6.0, along with the ‘State of Work’ document on the PhEur EDQM website, and also the General Information Chapter 8 in the JP XV. Kollidon VA 64 has a spherical structure, with a high proportion of damaged spheres. The shell-like structure reduces flowability, but the damaged spheres cover a greater surface area of the filler particles, increasing the efficacy of its use as a dry binder.(9) Furthermore, when used in transdermal drug delivery systems, copovidone has been shown to significantly alter the melting behavior, by reducing the heat of fusion and the melting point of estradiol and various other sex steroids.(10) Plasdone S-630 has been used in direct compression experiments with active substances that are difficult to compress, such as acetaminophen (paracetamol); and has been shown to produce harder tablets than those containing the same actives but made with microcrystalline cellulose.(11) In general, copovidone has better plasticity than povidone as a tablet binder, and is less hygroscopic, more elastic, and less tacky in film-forming applications than povidone. Up to about 1975, copovidone was marketed by BASF under the name Luviskol VA 64. Luviskol is currently used only for the technical/cosmetic grade of copovidone.