Cas-No: 9003-39-08
Einecs: 1312995-182-4
Composition: Copovidone, vinylpyrrolidone-vinyl acetate
Dosage Form: Capsules, Granules, Tablets
Function: Binder, coating, Crystallisation inhibitor, Direct compression, film former, Moisture protection, Solubility enhancement, Wetting-dissolution enhancement
Kollidon VA 64 is a white or slightly yellowish, free-flowing powder with a faint characteristic odor and practically no taste.
Kollidon VA 64 readily dissolves in all hydrophilic solvents.
Solutions of more than 10 % concentration can be prepared in water, ethanol, isopropanol, methylene chloride, glycerol and propylene glycol.
Kollidon VA 64 is less soluble in ether, cyclic, aliphatic and alicyclic hydrocarbons.
Kollidon VA 64 is a vinylpyrrolidone-vinyl acetate copolymer that is soluble both in water and in alcohol.
Kollidon VA 64 is used as a dry binder in tabletting, as a granulating auxiliary and as a film-forming agent in the pharmaceutical industry
Kollidon VA 64 can also be used as a binder in wet granulation for the production of tablets and granules, since it is readily soluble in all the usual solvents.
Kollidon VA 64 can then be added either as a solution during granulation, or dry to the other ingredients, in which case the solvent is added alone during granulation.
Trials so far conducted with both methods, using equal quantities of liquid, produced tablets of much the same hardness.
A combination of the two methods, i.e. mixing some of the Kollidon VA 64 with the active ingredient, and dissolving the rest in the solvent, sometimes gives the best results.
This is particularly recommended if the active ingredient does not readily absorb the solvent.
Since it is less hygroscopic than povidone (e.g. Kollidon 25 or 30), Kollidon VA 64 gives granules that have less tendency to stick to the punches of the tabletting machine, when operating under humid conditions.
The binding power of Kollidon VA 64 is comparable to that of Kollidon 25 and Kollidon 30.
Features of Kollidon VA 64:
-Excellent for high humidity exposure
-Excellent for peroxide sensitive actives
Applications of Kollidon VA 64:
-Solid Dosage
-Tablets
-Capsules
-Wet Granulation
-Solid Dispersions
-Hot Melt Extrusion (HME)
-Semi-solid Dosage
-Transdermal Films
Benefits of Kollidon VA 64:
Kollidon VA 64 provides erodible instant release matrix
Kollidon VA 64 is a solubilizer, dispersant, crystallization inhibitor and matrix former
For direct compression, roller compaction and wet granulation, suitable for markets with higher humidity exposure
Kollidon VA 64 has excellent stability throughout the extrusion process
A coarse powder provides a dust free handling, good flowability and faster extruder feeding
Recently obtained GRAS/SA status (Generally Recognized As Safe/Self-Affirmed) by the U.S. Food & Drug Administration (FDA) for use in food and nutritional supplements e.g. vitamin and mineral tablets
Description of Kollidon VA 64:
White or slightly yellowish, free-flowing powder with a faint characteristic odour and practically no taste.
Kollidon VA 64 is a vinylpyrrolidone-vinyl acetate copolymer that is soluble both in water and in alcohols.
Kollidon VA 64 is used in the pharmaceutical industry as a binder in tablets, as a granulating agent, as a retarding agent and as a film-forming agent.
Kollidon VA 64 is available as Product No. 95405-2-43.
For further details that are beyond the scope of this leaflet, please consult the book, “Kollidon – Polyvinylpyrrolidone for the Pharmaceutical Industry” 4th edition 1999.
Identity: Conforms
Clarity of the solution (10 % in water): No more opalescent than reference suspension III
Colour of the solution (10 % in water): No darker than B5, BY5 or R7
K-value (nominally 28): 25.2 – 30.8
Relative viscosity (1% in water): 1.178 –1.255
Nitrogen: 7.0 – 8.0 %
Loss on drying : 5.0%
Vinylpyrrolidone (by HPLC): 10 ppm
Vinyl acetate (by HPLC): 10 ppm
Monomers VP + VAc (by titration): 0.4%
Saponification value: 230 – 270
Sulfated ash: 0.1%
Heavy metals: 10 ppm
pH value (10 % in water): 3 – 7
Peroxides: 400 ppm
Hydrazine: 1 ppm
Vinyl acetate, polymerized: 35.3 – 41.4%
Acetaldehyde (enzymatic determination): 500 ppm
Kollidon VA 64 is a white or slightly yellowish, free-flowing powder with a faint characteristic odor and practically no taste.
KEYWORDS:
9003-39-08, 1312995-182-4, Kollidon, Kollidon VA, Copolyvidone, Copovidone, VP/VAc copolymer 60/40, copolymer of 1-vinyl-2-pyrrolidone and vinyl acetate in a ratio of 6 : 4 by mass, Conforms, Nitrogen
Kollidon VA 64 & VA 64 Fine are vinylpyrrolidone-vinyl acetate copolymers or copovidone.
Due to Kollidon VA 64s exceptionally high binding capacity, Kollidon ® VA 64 can be used as a dry binder for direct compression tableting and as a soluble binder for granulation; these properties make it an attractive and cost-effective alternative to natural binders.
In addition, Kollidon VA 64 is ideal as a solubilizer in hot-melt extrusion processes.
Kollidon VA 64 fine is specifically designed for roller compaction and binding in DC formulations.
Solubility Kollidon VA 64 readily dissolves in all hydrophilic solvents.
Solutions of more than 10 % concentration can be prepared in:
-water
-ethanol
-isopropanol
-methylene chloride
-glycerol
-propylene glycol
Kollidon VA 64 is less soluble in:
-ether
-cyclic, aliphatic and alicyclic hydrocarbons.
Viscosity of Kollidon VA 64:
The values were determined at 25 °C in a capillary viscometer.
They represent typical values.
Particle size distribution of Kollidon VA 64:
The following values were determined with an air-jet sieve and should be regarded as typical values.
Finer than 50 µm approx. 15 %
Coarser than 250 µm approx. 1 – 2 %
Bulk density of Kollidon VA 64:
The bulk density of Kollidon VA 64 usually lies in the 0.2 – 0.3 g/ml range.
Hygroscopicity of Kollidon VA 64:
Kollidon VA 64 absorbs only about one third of the quantity of water absorbed by povidone, e.g. Kollidon 30.
Molecular weight of Kollidon VA 64:
The average molecular weight is usually expressed as a K value.
The exact weight-average molecular weight, Mw of the product is best determined by measuring the light scatter of a solution.
Values in the range of 45,000 – 70,000 have been determined for Kollidon VA 64.
Stability, storage of Kollidon VA 64:
Kollidon VA 64 can be stored at room temperature (max. 25 °C) in the unopened original containers for at least 3 years.
The storage temperature should be kept below 25 °C.
General:
Copovidone has been used for decades in the pharmaceutical industry in Europe.
Up to about 1975 Kollidon VA 64 was marketed under the name of Luviskol VA 64, which today is used only for the technical/cosmetic grade of this copolymer.
This is why older publications often refer to the use of Luviskol VA 64 in pharmaceuticals.
Binder for tablets and granules of Kollidon VA 64:
Kollidon VA 64 is an excellent binder for tablets and granules.
Between 2% and 5%, as a proportion of the final weight of the preparation, is usually used.
An important property of Kollidon VA 64 in this application is its plasticity, which distinguishes it from povidone (e.g. Kollidon 30).
This property often gives granules and mixtures that are less susceptible to capping during tabletting, and tablets that are less brittle.
Dry binder for compression of Kollidon VA 64:
Kollidon VA 64 has been found to be the best dry binder for direct comdirect pression that gives much better results than any of the povidone grades.
Kollidon VA 64 can be added to materials such as sorbitol, mannitol, starch, or direct compression aids, e.g. microcrystalline cellulose, whose own binding strength is inadequate, to give tablets with very good properties.
The literature contains a large number of vitamin formulations with Kollidon VA 64.
Pharmacopoeias of Kollidon VA 64:
Kollidon VA 64 fulfils the requirements of the current Ph. Eur. monograph,“Copovidone” and the JPE monograph, “Copolyvidone”.
A DMF with the number 6745 has been drawn up in the USA.
It also meets the requirements of the USP-NF draft monograph „Copovidone“ published in 1998.
Infrared spectrum of Kollidon VA 64:
The infrared spectrum was obtained with a tablet of Kollidon VA 64 in potassium bromide.
Arrows indicate where the spectrum differs from that of povidone.
Film-coating Kollidon VA 64 forms films that are soluble at all pH values.
They are less hygroscopic and more elastic than those formed by povidone (e.g. Kollidon 30).
Nevertheless, Kollidon VA 64 usually still absorbs too much water, so that it can seldom be used as the sole film-forming agent in a formulation.
It is therefore recommended to combine it with less hygroscopic substances such as cellulose derivatives, shellac or polyethylene glycol (e.g. Lutrol® E 6000). Plasticizers are normally not required.
The formulations in Tables 5 and 6 are typical formulations for tablet coatings.
They were tested on 9 mm diameter, 3.4 mm thick, 200-mg placebo tablet cores in the laboratory.
Kollidon VA 64 significantly improves their brittleness and solubility when it is combined with cellulose derivatives.
When it is used in film coatings based on shellac, the properties of the film are more consistent.
Subcoating of Kollidon VA 64:
If it is intended to coat tablet cores with aqueous solutions or suspensions, it is recommended to provide them with a barrier if they contain a water-sensitive active ingredient or a highly effective disintegrant (e. g. Kollidon CL) that is activated by water.
This also applies if the cores are too soft or if their adhesive properties are inadequate for aqueous coatings.
The cores are warmed to about 35 °C and sprayed with a 10 % solution of Kollidon VA 64 dissolved in an organic solvent, e.g. isopropanol, ethanol, ethyl acetate or acetone.
As soon as a barrier film of adequate thickness has been built up, the aqueous coating can be applied.
It has been found that 0.4 mg Kollidon VA 64/cm2 is adequate.
Sugar-coating of Kollidon VA 64:
Kollidon VA 64 is used in sugar-coating to improve the adhesion of the coating to the surface of the tablet core and to increase the capacity of the coating solution for pigments and improve their dispersibility.
However, Kollidon VA 64 helps not only in the application of sugar coatings but also in the automation of the sugar-coating process.
Sprays of Kollidon VA 64:
Because of its good film-forming properties, Kollidon VA 64 can also be used in topical sprays.
The formulation in Table 7 provides a typical example of a spray bandage.
Kollidon VA 64 and Kollidon VA 64 Fine are vinylpyrrolidone-vinyl acetate copolymers which are soluble both in water and in alcohols.
They are used in the pharmaceutical industry as binders in tablets and as granulating, retarding and fi lm-forming agents.
Kollidon VA 64 and Kollidon VA 64 Fine are white or slightly yellowish, free-fl owing powders with a faint characteristic odor and practically no taste.
The study evaluates use of Kollidon VA 64 and a combination of Kollidon VA 64 with Kollidon VA 64 Fine as excipient in direct compression process of tablets.
The combination of the two grades of material is evaluated for capping, lamination and excessive friability.
Inter particulate void space is higher for such excipient due to the hollow structure of the Kollidon VA 64 particles.
During tablet compression air remains trapped in the blend exhibiting poor compression with compromised physical properties of the tablets.
Composition of Kollidon VA 64 and Kollidon VA 64 Fine is evaluated by Design of Experiment (DoE).
A Scanning Electron Microscopy (SEM) of two grades of Kollidon VA 64 exhibits morphological differences between coarse and fine grade.
The tablet compression process is evaluated with a mix consisting of entirely Kollidon VA 64 and two mixes containing Kollidon VA 64 and Kollidon VA 64 Fine in ratio of 77:23 and 65:35.
A statistical modeling on the results from the DoE trials resulted in the optimum composition for direct tablet compression as combination of Kollidon VA 64 and Kollidon VA 64 Fine in ratio of 77:23.
This combination compressed with the predicted parameters based on the statistical modeling and applying main compression force between 5 - 15 kN, pre-compression force between 2 - 3 kN, feeder speed fixed at 25 rpm and compression range of 45 - 49 rpm produced tablets with hardness ranging between 19 - 21 kp, with no friability, capping or lamination issue.
Synonyms:
Copolyvidone
Copovidone
VP/VAc copolymer 60/40
copolymer of 1-vinyl-2-pyrrolidone and vinyl acetate in a ratio of 6 : 4 by mass.