Determination of povidone

A simple and rapid method for the quantitative determination of povidone is by photometry of the povidone-iodine complex [18,19] ... 

Fig. 25. Calibration curves for the photometric determination of povidone K 17, povidone K 30 and povidone K 90 with iodine...

Table 54. Photometric determination of povidone K 25 in the presence of different compounds [ 18]... 

Methods for the determination of povidone in contact lens fluids with the aid of Congo Red [142] as well as a fluorimetric method that uses anilinenaphthaline sulfonate [111,181] are described in the literature. 

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]. 

The intrinsic viscosity of unfractionated povidone can be determined by various methods [212]. In Fig. n, the intrinsic viscosity of povidone K 30 is determined by extrapolation to zero concentration of measurements at different concentrations, giving a value of 0.207 dl/g. 

Fig. 11. Determination of the intrinsic viscosity [h] of povidone K 30 in water by extrapolation [212]...

The molecular weight distribution of povidone can best be determined with the aid of high-performance gel permeation chromatography. Figure r9 gives a qualitative comparison between povidone K 17 and povidone K 30 in a gel permeation chromatogram marked at a molecular weight of 35 000. 

Fig.20. Molecular weight distribution curve of povidone K 17 (Kollidon 17 PF) with integral curve, determined by GPC...

Electrophoresis has also been described in the literature as a technique for determining the molecular weight distribution of povidone [377]. 

The osmotic pressure of solutions is of particular importance with parenteral administration. (In the case of the human blood serum it is about 7.5 bar at 37 °C.) It is not very affected by the molecular weight and the concentration of povidone. The simplest method for determining the osmotic pressure uses the Van t Hoff equation. 

As the molecular weight determines many of the properties of povidone that affect its use, it is worth knowing that it is not changed by storage or heating. In... 

The most important and clearest means of identification is provided by the infrared spectrum. It is the same for all types of povidone. Figure 24 shows the infrared spectrum of povidone K 90, and Fig. 99 shows the infrared spectra of povidone K 30 (Section 4.3.1.1). The only disadvantage of this method of identification lies in the fact that crospovidone gives the same spectrum (see Section 3.3.1.1). However, the difference can readily be determined from the solubility. 

Methods for determining the purity of povidone are described in detail in the European, U.S. and Japanese pharmacopoeias. They cover all the parameters listed in Table 32. 

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

The content of 2-pyrrolidone and N-vinylpyrrolidone was determined in povidone before and after addition of two different amounts of the reference substances (Table 38). 

As the titration method for the determination of acetaldehyde is very unspecific and measures more than just aldehydes or acetaldehyde, the following specific enzymatic method is recommended. It was introduced in the harmonized monograph of povidone in Ph.Eur., USP and JP. 

The acetaldehyde content of a sample of povidone K 30 was determined 6 times. The values found, the average and the relative standard deviation are given in Table 43. 

To a sample of povidone (Kollidon 30 batch 822) different amounts of acetaldehyde-ammonia trimer (=Hexahydro 2.4.6-trimethyl 1.3.5 triazine, C6H15N3 3H20, CAS number 76231-37-3, available at Fluka/Sigma Aldrich) were added and determined enzymatically. The acetaldehyde in this Kollidon batch was 45 mg/kg before the addition (Table 44). 

The formic acid content of povidone (batch 719 of Kollidon 30) was determined in 5 times (Table 46). 

To the same batch 719 of povidone K 30 different known amounts of formic acid were added and determined (Table 47). 

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

GC Determination of(hydroxy-methyl)-butylpyrrolidone (= "2-propanol-vinylpyrrolidone adduct") in low-molecular povidone... 

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

A UV-spectrophotometric determination of more than 20% of povidone K 30 in mixtures with active ingredients was developed by multicomponent analysis [618]. 

Povidone K 25 and povidone K 30 are suitable for comilling, while the average molecular weight of povidone K 90 could decrease under prolonged mechanical stress. As a rule, the mixtures are milled for one hour, though the best time must be determined individually for each active substance. 

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. 

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. 

M Winicov, EL Winicov. Determination of free iodine and its significance in povidone-iodine solution. Proc Int Symp Povidone April 17-20 186-192, 1983. 

Eor accurate standardization of solutions, the water content of the solid povidone must be determined before use and taken into account for any calculations. A specification for povidone is contained in the Food Chemicals Codex (FCC). 

Low-molecular povidone can be polymerized in 2-propanol and in such case it contains the radical 2-propanol-vinylpyrrolidone adduct (hydroxy-methyl)-butylpyrrolidone as impurity (structure and determination see Section 2.3.3.8). The level of this impurity depends on the average molecular weight. 

As these methods of determining the average molecular weight are relatively complicated, for povidone it is expressed in terms of the K-value, in accordance with the European and U.S. Pharmacopoeias (see also Section 2.2.3.2). 

The number-average of the molecular weight, Mn is determined by methods that measure the number of molecules. This value is very seldom determined or published for povidone. Table 17 shows some older values. 

It is important that injection solutions that contain low-molecular povidone can be sterilized by filtration. The feasibility of filtering these solutions is mainly determined by the concentration of these povidone grades. The viscosity evidently plays a subordinate role, as this is always less than 5 mPa s for povidone K17 up to a concentration of 15% in water. With povidone K 12 it is even lower (see Section 2.2.3.1). Taking a batch of Kollidon 17 PF as an example, it can be seen from Fig. 23 that the filtration time depends very much on the concentration. The... 

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