endobj 5 0 obj 7 0 obj /MediaBox [0.000 0.000 1224.000 792.000] << /Type /Outlines /Count 0 >> For testing solubility in medium, the starting concentration is 20,000 mg/ml (i.e., 20 mg/mL) in Tier 1, but for DMSO and ethanol the starting concentration is 200,000 mg/ml (i.e., 200 mg/mL) in Tier 2. 82 The pH-solubility profile of the API should be determined over the pH range of 1.2–6.8. endobj stream ¾Equilibrium (= thermodynamic) solubility (S) the concentration of compound in a saturated solution when solid is present and solution and solid are at equilibrium ¾Intrinsic solubility (So) the equilibrium solubility of the free acid or base form of an ionizable compound at a pH where it is fully unionized ¾Apparent solubility (SpH) 3.1 Intrinsic rate of dissolution /Annots [ 10 0 R 12 0 R ] USP and BP solubility criteria. ] Determination of Thermodynamic Solubility of Active Pharmaceutical Ingredient for Veterinary Species Dogs –Media composition: buffer according to USP –pH: 1.2, 4.6, and 6.8 –Temperature: 39°C Cattle –Media composition: pH 2.5 HCl, pH 3.5 acetate buffer, pH 5.0 phosphate buffer and volatile fatty acids (VFA), pH 6.8 phosphate >> endobj 3 + C P D F) /Pages 3 0 R >> 2 0 obj 6 0 obj << /Filter /FlateDecode There is no substantial analysis performed on the Shear distributions for USP 25, the rotating disc. x��Zےܶ}�W�Q�Z�$x]�TY7;�r��*O��3�YZ3�1��z�!�ޜ�p����[email protected]��n�A�4I�T�O����٫*/�4�T�ˤ�k�a��{�Uf�T}�W����t^�]���]���'�K�N�;t�yz���z��ٵ����F=�T��~U�7��}���$�juP�TI�?�W���Kg+�'yVzg�w��өSýz?Ls�}���⌂�\�ūՏݱ۽z�О�nT��a:u��g�z8�y�.��:iL�\���O_�. The information is provided for those who use, prepare, and dispense drugs, solely to indicate descriptive and solubility properties of … Descriptive term: Part of solvent required per part of solute: Very soluble: Less than 1: Freely soluble: From 1 to 10: Soluble: From 10 to 30: Sparingly soluble: From 30 to 100: Slightly soluble: From 100 to 1000: Very slightly soluble: From 1000 to 10,000: Practically insoluble: 10,000 and over: Follow us: The solubility of one substance in another is a measure of the degree of molecular mixing between the two pure substances at thermodynamic equilibrium. >> [/PDF /Text ] The similarities to USP Apparatus II (same vessel as the rotating disk but a paddle ... solubility and bulk concentration respectively, A is the surface area and h is the … /ProcSet 4 0 R /Length 3283 >> /MediaBox [0.000 0.000 1224.000 792.000] The ability to accurately measure the aqueous solubility of a material is affected by the physico-chemical properties of the material (e.g., surface area, particle size, crystal form), the properties of the solvent (e.g., pH, polarity, surface tension, added surfactants, co-solvents, salts), and the control of the solubility measurement parameters (e.g., temperature, time, agitation method). /F1 8 0 R 83 Measurements should be made in triplicate under at least three pH conditions, pH 1.2, 4.5 and 6.8 Nifedipine is a dihydropyridine calcium channel blocking agent. /Resources << /Count 2 The rate of dissolution will affect the time required to reach equilibrium, but will not affect the final equilibrium solubility… The “description” and “solubility” statements pertaining to an article (formerly included in the individual monograph) are general in nature. Nifedipine inhibits the transmembrane influx of extracellular calcium ions into myocardial and vascular smooth muscle cells, causing dilatation of the main coronary and systemic arteries and decreasing myocardial contractility. << /Type /Page • USP 1092 1.1 Performing Filter Compatibility 1.2 Determining Solubility and Stability of Drug Substance in Various Media 1.3 Choosing a Medium and Volume 1.4 Choosing an Apparatus • METHOD DEVELOPMENT 2.1 Deaeration 2.2 Sinkers 2.3 Agitation 2.4 Study Design 2.4.1 Time Points 2.4.2 Observations 2.4.3 Sampling 2.4.4 Cleaning 82 The pH-solubility profile of the API should be determined over the pH range of 1.2–6.8. << /Type /Pages /Kids [6 0 R << /Type /Catalog /F2 9 0 R 83 Measurements should be made in triplicate under at least three pH conditions, pH 1.2, 4.5 and 6.8 /Outlines 2 0 R /Contents 7 0 R Working document QAS/17.699 page 4 80 de-aggregation of the particles with agitation or sonication (3).Once wetting is successfully 81 achieved, the solubility experiment should proceed toward equilibrium.