Determination of copovidone

Most of the colour and precipitation reactions described in the literature for soluble polyvinylpyrrolidone can be used in the qualitative determination of copovidone (Table 160). 

The method for the quantitative determination of copovidone given by the Ph.Eur. monograph measures the nitrogen content (theoretical value 7.1%) by the Kjeldahl method. 

Fig. 100. Calibration curve for the photometric determination of copovidone with iodine [18]...

Table 171. Determination of copovidone substances and auxiliaries [18] as the iodine complex in the presence of active ...

The ratio of n to m is approximately n = 1.1m. Molecular weights of 45 000-70 000 have been determined for KolUdon VA 64. The average molecular weight of copovidone is usually expressed as a K-value. 

HPLC method for the determination of free N-vinylpyrrolidone, 2-pyrrolidone and vinyl acetate in povidone and copovidone... 

The content of 2-pyrrolidone, N-vinylpyrrolidone and vinyl acetate was determined in copovidone before and after addition of different amounts of the reference substances (Table 39). 

GC Determination of 2-propanol (isopropanol) in low-molecular povidone and in copovidone... 

As these methods of determining the average molecular weight are relatively time-consuming, that of copovidone is now expressed in terms of the K-value, in accordance with the European and U.S. Pharmacopoeia methods for povidone. 

The number-average of the molecular weight, Mn is determined by methods that measure the number of molecules. Values of copovidone recently determined by this method lie between 15000 and 20000. 

The photometric determination of the iodine complex used to determine povidone can also be used for copovidone, though the colour intensity of the iodine complex only reaches its maximum after about 30 min, after which it slowly fades. Thus, it must be measured after 30 min, instead of 10 min, as in the determination of povidone [18]. 

A calibration curve must be established to determine the copovidone content from the absorbance (Fig. 100). The absorbance of the iodine complex is slightly less than that of the povidone-iodine complex. 

Methods for determining the purity of copovidone are described in the corresponding monograph of Ph.Eur. The parameters measured are those given in Table 162. 

GC Determination of(hydroxy-methyl)-butylpyrrolidone (= "2-propanol-vinyl-pyrrolidone adduct") in copovidone... 

The gaschromatographic method for the determination of HMBP in copovidone is exactly the same method as described in Section 2.3.3-7 for the low-molecular povidones. 

In addition to the validation tests reported in Section 2.3.3.7 the recovery rate was determined using copovidone. The content of the 2-propanol-vinyl-pyrrolidone adduct (HMBP) was determined twice on one batch before and after addition of different amounts of HMBP. Table 167 shows the results. 

In these tests, aqueous solutions containing 50,100 and 200 pg of copovidone and 20 times the quantity of the tablet ingredients listed in Table 171 were prepared, and their copovidone content determined. 

The optimum quantity of solvent can best be determined from the power consumption of the granulator, though it must be noted that this can vary considerably, even with the same active substance, depending on its origin [484] (Table 61). For the comparison with copovidone see Section 4.4.2.2. 

The average molecular weight of povidone and copovidone is expressed in terms of the K-value, in accordance with the Pharmacopoeias that apply in Europe and the USA [13]. It is calculated from the relative viscosity in water. The same methods can be applied to copovidone, and they give K-values between the limits given in Section 4.2.I.2. They are based on the relative viscosity of a 1% solution in water at 25°C. The relationship between the K-value and the relative viscosity is shown in Fig. 91. The curve was obtained using the method of determination and calculation described in Section 2.3.2.1. 

As the amount of water absorbed from the air is particularly important in film coating, this was determined with cast copovidone films that contained 2.5% glyc-... 

The N-vinylpyrrolidone and vinyl acetate contents of a copovidone sample were determined 6 times. The values found and the average are given in Table 164. 

The content of the residual solvent acetic acid in copovidone is determined by the following HPLC method using acetic acid as external standard. 

The most versatile method for quantitatively determining copovidone is probably the photometric measurement of the iodine complex described in Section 4.3.I.2. It has been successfully tested on samples that also contained a series of auxiliaries and active substances, to verify its suitability for preparations. 

The capacity of the powder mixture to bind liquid is one of the parameters that can be used to determine the quantity of binder solution required in wet granulation. Every powder mixture to be granulated has a different adsorption capacity for the solvent or the copovidone solutions, which most effectively minimizes the proportion of fines [483]. 

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