A copovidone used in granulation and as a dry binder in tablets, capsules and granules, as a film-forming agent in tablet coatings and subcoatings, and as a film-forming agent in topical sprays. Soluble copovidones are widely used for instant release formulation and is suitable in hot melt extrusion processes
Kollidon® VA 64 is a vinylpyrrolidone-vinyl acetate copolymers. It is used as dry binders for direct compression tableting, as granulating agents, as retarding and as a film-forming agents as well as in taste-masking applications. As copovidone with an 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, it is ideal as a solubilizer in hot-melt extrusion processes. Kollidon® VA 64 is especially suitable for markets with higher humidity exposure.
Binder for tablets and granules
Kollidon® VA 64 is an excellent binders for tablets and granules. Between 2% and 8%, as a proportion of the final weight of the preparation, is usually used. An important property of Kollidon® VA 64 in this application is the plasticity, which distinguishes the products from povidone (e.g. Kollidon® 30). This property often gives granules and mixtures that are less susceptible to capping during tableting, and tablets that are less brittle.
Dry binder for direct compression
Kollidon® VA 64 have been found to be excellent dry binders for direct compression. The hardness, friability, porosity and disintegration time of lactose and starch placebo tablets produced with Kollidon® VA 64 are directly related to the compression force used. Kollidon® VA 64 can be added to materials such as sorbitol, mannitol, starch, or direct compression aids, e.g. micro crystalline cellulose, whose own binding strength is inadequate, to give tablets with very good properties.
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. It 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 tableting machine, when operating under humid conditions. The binding power of Kollidon® VA 64 is comparable to that of Kollidon® 25 and Kollidon® 30.
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. Plasticizers are normally not required. 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.
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.
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.
Because of its good film-forming properties, Kollidon VA 64® can also be used in topical sprays.
Kollidon® VA 64 is frequently cited in the literature as a matrix material for instant release and for sustained release dosage forms. Formulations with cellulose derivatives, polyacrylic acid, stearyl alcohol or polyhydroxyethyl methacrylate have been described for sustaining or controlling release. The formulations can be treated in various ways, e.g. freeze-dried or extruded, to produce a granulate, or melted and extruded, to produce pellets. Any relevant patents must be respected.
Hot melt extrusion processes
The solubility and bioavailability of poorly soluble APIs is often enhanced when they are molecularly dispersed in a polymeric carrier. This makes hot melt extruision (HME) a valuable technology for the pharmaceutical industry – and opens new doors for formulators working with promising actives that cannot otherwise be solubilized. HME also grants manufacturers a great amount of flexibility, as the viscous fluid obtained from the extrusion process can be directly shaped into any desired form. In addition, the extrudates usually have a high density, which makes them suitable for producing controlled-release dosage forms. Kollidon® VA 64 is especially suitable for hot melt extrusion processes. In matrices it acts as solubilizing agent, dispersant, crystallization inhibitor as well as is suitable in immediate-release matrices.