Applications of crospovidone

Gravimetric analysis provides the best method for the quantitative determination of normal crospovidone in preparations. 

Suspend the sample material in water and/or a suitable solvent that dissolves all the other components of the preparation. Crospovidone is determined gravimet-rically after filtration and drying. 

Accurately weigh about 5 g of sample, that contains 2-5% of crospovidone, into a glass beaker and mix with about 250 ml of water or other solvent. Insert a magnetic stirrer bar and cover the beaker with a clock glass. Stir for 2 hours. 

Then leave to settle and draw off the supernatant solution through a dried and preweighed G 4 Gooch crucible. Wash and leave to stand again, decant the supernatant solution through the Gooch crucible, then quantitatively transfer the residue to the Gooch crucible with small portions of water. 

0/0 Crospovidone = Weight after filtration [g] x 100 Original sample weight [g] 

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Methods Nos. 1 and 2 in Table 132, in which the disintegrant is added after granulation, are used most frequently. In Methods Nos. 3 and 4, the disintegrant is added prior to granulation, while in Nos. 5 and 6 part of the disintegrant is added before, and the rest after granulation. Direct compression, Method No. 7, can also be used. The application of crospovidone in the roller compaction technology (Method No. 6) is described in the literature [650,651]. 

Hlpasawa N, Ishise S, Miyata M, Danjo K. Application of nilvadipine solid dispersion to tablet formulation and manufacturing using crospovidone and methylcellulose on dispersion carriers. Chem Pharm Bull 2004 52(2) 244-247. 

One of the most important properties of crospovidone in its applications is its ability to swell in a predictable manner without forming a gel. A number of methods are described in the literature for measuring swelling, the most important being listed in Table 119. 

Table 121. Applications of normal and micronized crospovidone as complexing agent in drugs...

An antibiotic dry syrup formulation is shown in Table 143 as an application of micronized crospovidone of low bulk density. The formulation has been developed in the laboratory for two different drugs, so that it can be regarded as a typical guide formulation. It contains citric acid, to adjust the pH to 4.9, to optimize the chemical stability of the drug, ampicillin trihydrate or amoxicillin trihydrate. 

As early as 1968, a patent was granted for the use of insoluble polyvinyl pyrroli-done as an active substance for treating certain stomach and intestinal disorders [125]. Pharmaceutical products containing micronized crospovidone as an active substance have been sold in France since the 70s on the basis of the results in a series of publications [443-454]. They contain 2g of crospovidone per dose, which, in one case, is combined with karaya gum as a further active substance. The functions and medical indications listed in Table 146 are to be found in the clinical literature and with the pharmaceutical products. This application of micronized crospovidone is based on the local effect on the mucous membrane, as opposed to a systemic effect, as it is insoluble and therefore not absorbed. This is why practically no side-effects are listed. 

The crospovidones are easily compressed when anhydrous hut readily regain their form upon exposure to moisture. This is an ideal situation for use in pharmaceutical tablet disintegration and diey have found commercial application in this technology. PVP strongly interacts with polyphenols, the crospovidones can readily remove them from beer, preventing subsequent interaction with beer proteins and the resulting formation of haze. The resin can be recovered and regenerated with dilute caustic. 

A number of different grades of lactose are commercially available that vary in their physical properties and many studies have been reported in the literature comparing the behavior of these various materials in different formulations. A number of co-processed excipients which contain lactose are available for direct-compression applications co-processed lactose and starch (Starlac, Meggle/Roquette Freres), lactose and microcrystalline cellulose Microcelac, Meggle) lactose and cellulose powder (Cellactose, Meggle), lactose, povidone, and crospovidone (Ludipress, BASF). 

Further, micronized crospovidone is of considerable significance as an active substance against diarrhoea in certain parts of the world. Micronized crospovidone grades of different bulk densities and different applications are available in the market. 

Table 117 gives the typical values for the bulk density and tap density for all crospovidone grades available in the market. The major differences in the bulk densities of the micronized/fine powder grades have an important effect on their applications. 

In 1987 the World Health Organization (WHO + FAO) specified an Accepted Daily Intake (ADI) value for soluble polyvinylpyrrolidone (povidone) in food of 0-50 mg/kg body weight [372]. For Crospovidone the ADI value is not specified and therefore no limit is given for the application in foods [215]. 

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