2.2. Physical and physicochemical methods

基本信息

• 标准
  欧洲药典
• 版本
  EP8.0
• 来源
  VOLUME 1
• 分类
  GENERAL CHAPTERS
• 页码
  21

EUROPEAN PHARMACOPOEIA 8.02.2.1. Clarity and degree of opalescence of liquids 2.2. PHYSICAL AND PHYSICOCHEMICAL METHODS 01/2008:20201 2.2.1. CLARITY AND DEGREE OF OPALESCENCE OF LIQUIDS VISUAL METHOD Using identical test-tubes of colourless, transparent, neutral glass with a flat base and an internal diameter of 15-25 mm, compare the liquid to be examined with a reference suspension freshly prepared as described below, the depth of the layer being 40 mm. Compare the solutions in diffused daylight 5 min after preparation of the reference suspension, viewing vertically against a black background. The diffusion of light must be such that reference suspension I can readily be distinguished fromwater R, and that reference suspension II can readily be distinguished from reference suspension I. Aliquidisconsideredclearif its clarity is the same as that ofwater Ror of the solvent used when examined under the conditions described above, or if its opalescence is not more pronounced than that of reference suspension I. Hydrazine sulfate solution.Dissolve1.0gofhydrazine sulfate Rinwater Rand dilute to 100.0 mL with the same solvent. Allow to stand for 4-6 h. Hexamethylenetetramine solution.Ina100mL ground-glass-stoppered flask, dissolve 2.5 g of hexamethylenetetramine Rin 25.0 mL ofwater R. Primary opalescent suspension(formazin suspension). To the hexamethylenetetramine solution in the flask add 25.0 mL of the hydrazine sulfate solution. Mix and allow to stand for 24 h. This suspension is stable for 2 months, provided it is stored in a glass container free from surface defects. The suspension must not adhere to the glass and must be well mixed before use. Standard of opalescence.Dilute15.0mLoftheprimary opalescent suspension to 1000.0 mL withwater R.This suspension is freshly prepared and may be stored for up to 24 h. Reference suspensions. Prepare the reference suspensions according to Table 2.2.1.-1. Mix and shake before use. Table 2.2.1.-1 IIIIIIIV Standard of opalescence 5.0 mL 10.0 mL 30.0 mL 50.0 mL Water R95.0 mL 90.0 mL 70.0 mL 50.0 mL Turbidity standard. The formazin suspension prepared by mixing equal volumes of the hydrazine sulfate solution and the hexamethylenetetramine solution is defined as a 4000 NTU (nephelometric turbidity units) primary reference standard. Reference suspensions I, II, III and IV have values of 3 NTU, 6 NTU, 18 NTU and 30 NTU respectively. Stabilised formazin suspensions that can be used to prepare stable, diluted turbidity standards are available commercially and may be used after comparison with the standards prepared as described. Formazin has several desirable characteristics that make it an excellent turbidity standard. It can be reproducibly prepared from assayed raw materials. The physical characteristics make it a desirable light-scatter calibration standard. The formazin polymer consists of chains of different lengths, which fold into random configurations. This results in a wide assay of particle shapes and sizes, which analytically fits the possibility of different particle sizes and shapes that are found in the real samples. Due to formazin’s reproducibility, scattering characteristics and traceability, instrument calibration algorithms and performance criteria are mostly based on this standard. INSTRUMENTAL METHODS INTRODUCTION The degree of opalescence may also be determined by instrumental measurement of the light absorbed or scattered on account of submicroscopic optical density inhomogeneities of opalescent solutions and suspensions. 2 such techniques are nephelometry and turbidimetry. For turbidity measurement of coloured samples, ratio turbidimetry and nephelometry with ratio selection are used. The light scattering effect of suspended particles can be measured by observation of either the transmitted light (turbidimetry) or the scattered light (nephelometry). Ratio turbidimetry combines the principles of both nephelometry and turbidimetry. Turbidimetry and nephelometry are useful for the measurement of slightly opalescent suspensions. Reference suspensions produced under well-defined conditions must be used. For quantitative measurements, the construction of calibration curves is essential, since the relationship between the optical properties of the suspension and the concentration of the dispersed phase is at best semi-empirical. The determination of opalescence of coloured liquids is done with ratio turbidimeters or nephelometers with ratio selection, since colour provides a negative interference, attenuating both incident and scattered light and lowering the turbidity value. Theeffectissogreatforevenmoderatelycolouredsamples that conventional nephelometers cannot be used. The instrumental assessment of clarity and opalescence provides a more discriminatory test that does not depend on thevisualacuityoftheanalyst.Numericalresultsaremore useful for quality monitoring and process control, especially in stability studies. For example, previous numerical data on stability can be projected to determine whether a given batch of dosage formulation or active pharmaceutical ingredient will exceed shelf-life limits prior to the expiry date. NEPHELOMETRY Whenasuspensionisviewedatrightanglestothedirection of the incident light, the system appears opalescent due to the reflection of light from the particles of the suspension (Tyndall effect). A certain portion of the light beam entering a turbid liquid is transmitted, another portion is absorbed and the remaining portion is scattered by the suspended particles. If measurement is made at 90° to the light beam, the light scattered by the suspended particles can be used for the determination of their concentration, provided the number and size of particles influencing the scattering remain constant. The reference suspension must maintain a constant degree of turbidity and the sample and reference suspensions must be prepared under identical conditions. The Tyndall effect depends upon both the number of particles and their size. Nephelometric measurements are more reliable in low turbidity ranges, where there is a linear relationship between nephelometric turbidity unit (NTU) values and relative detector signals. As the degree of turbidity increases, notalltheparticlesareexposedtotheincidentlightand the scattered radiation of other particles is hindered on its way to the detector. The maximum nephelometric values at which reliable measurements can be made lie in the range of 1750-2000 NTU. Linearity must be demonstrated by constructing a calibration curve using at least 4 concentrations. TURBIDIMETRY The optical property expressed as turbidity is the interaction between light and suspended particles in liquid. This is an expression of the optical property that causes light to be scattered and absorbed rather than transmitted in a straight line through the sample. The quantity of solid material in suspension can be determined by the measurement of the General Notices (1) apply to all monographs and other texts21

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