The chapter also briefly describes typical experimental methods used to assess solubility determination of pharmaceutical materials. USP and BP solubility criteria. is determined by the volume of an aqueous medium sufficient to dissolve the highest dose strength of a dosage form across a pH range of 1.2–7.5. 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. endstream endobj startxref The composition of a saturated solution, expressed as a proportion of a designated solute in a designated solvent, represents this thermodynamic limit of solubility. 3082 0 obj <>/Filter/FlateDecode/ID[<6D5DE98C958B164A9A79B0061C870729>]/Index[3045 75]/Info 3044 0 R/Length 159/Prev 661891/Root 3046 0 R/Size 3120/Type/XRef/W[1 3 1]>>stream Less than 1. �w1.�� �L��!����Ěx�:Qf:��P��7I��2gn(0XW�)Q�� �xJT����k �ٸF�w�_3>�U��=Z�;�OF;��m�VgKn��L�[/�U�­�OͭT�8�(�4埌[�+�W;��}jM�)֭��ֲnMܞ%�?�hO�R�Wl���/�|��G���p����G�%?�Z{5�j��=�Z��֘�]Ժ���9��_*�$}4�����}��>�f2|,�ֲO�����x������W�=�sX�̯�? DJ��m� "U��$c�$;Z�n��ցMK����H��� 2[�2 ,+��=H�������� �ІaE�g��{ � &�� This chapter provides an overview of the concepts and equations that are relevant to solubility measurements. From 10 to 30. Very soluble. A drug substance should be classified as highly soluble when the highest dose strength is soluble in ≤250 mL of aqueous media over the pH range of 1–7.5 (5). %%EOF (�,Ir�:M�7tz��+�!��XD��k��Q,�*KNJu�V������������)��Ws/dJ�P��,(:/��Y�r��o�K5E49��"���&8 �Xb��y�7�j����&���j����W�>m�pt�8�x�Z췫�N�&��]��Ȧb��r'�xiX#�������i"���B�^Pq� �?��*@,����Aɤ�d4��)��L� *�ڙ�!�LJPq�� L��L ��d��R�"8�. A drug substance is classified as highly soluble when the highest dose strength is soluble in 250 mL or less of aqueous media over the pH range of … uY,�vdE���m�A�Q�h���8�s�XmT���"�ŬDG��(�6ZJ�l�m��~�}~Lh>� �ko�'8���*��u5.+�L��M�8^D������|4�]u�f�q��9'�Q�[��ۃŸ�|�ʂe�)X�£M�emɲ�dYZ��V'l�V#�'�V��[�:��oI Q��6�[email protected]��:sSV��%y��F��h�$����G'��F������:ސd/o�k��h��p�1�H����'Jb���#��R:�=*$�(}M�7͓�t̀��?��B����� ����_�6��S�+Nw The new USP General Chapter <1236> Solubility Determination was proposed in Pharmacopeial Forum 43(2) [March – April 2017. Background and objectives: The solubility of one substance in another is a measure of the degree of molecular mixing between the two pure substances at thermodynamic equilibrium. 3045 0 obj <> endobj The information is provided for those who use, prepare, and dispense drugs, solely to indicate descriptive and solubility properties of an article complying with monograph standards. soluble in 80% alcohol; insoluble in ether. he United States Pharmacopeia (USP) held the workshop “Solubility Criteria for Veterinary Products” on November 7–8, 2012, at USP headquarters (1). %PDF-1.5 %���� ea�hq``H���qf~��#T���c�V֢(G�w�.� {�fF�]�ʇ0 0 Descriptive term. Part of solvent required per part of solute. Soluble. From 1 to 10. 234 0 obj <> endobj 252 0 obj <<6CF34524EBAD4E01AEAA98CA12E8A4AB>]/Info 233 0 R/Filter/FlateDecode/W[1 2 1]/Index[234 38]/DecodeParms<>/Size 272/Prev 69030/Type/XRef>>stream Freely soluble. ���{Vn ��5�iH m���~�>��C�1�ϩ>�x�������B���gZ�D)� |h��x8'„�kBx(����Г����R�9,W�e#K>�]�^1�ϟ^>�e�L� ��4�M��� o⑲v�������!�����Wj� x�bbd``b`�$Z��6 ��$X����@�[email protected]�Q$6��bu�X �� u�@�;�UV�@b�&#C%�dF���0 �� 5 endstream endobj 271 0 obj <>stream z.,�� ���c��$����?��hZ��P�����S\�W��vizqø�{Y}l���nU�h��}�F��K����=|T˧�!��Bq!����Ɇ��G'�m����. FEBRUARY 201723. the volume of an aqueous medium sufficient to dissolve the highest dose strength in the pH range of 1–7.5. ���9S��X+�N�"�Vހ��1F��c��5zY�$�1�^ZϜ�Ԡ�8sFivQ�Ͳ1�=��r�T��ի�k����՛��;m�m5O��i������}8;R�Y�h����t��62���뛎iΓ�zɔ����U;�؞�ο]��MLrΙ��]Va$���o��xr���g�>� ^V���]X�ZU�u�}5��m�W]�o���:����`v=i������Á��_�:7HF�[��7 ���Y^8��" E)ȱg2���7� �P��@l�J���%8��#�h�[email protected]� �B D-�(��s��:J���c�a�����h� h��t�z��=��G�m�w��� �u�SC>%�� ��s�� ޛ8`w�w��#��N;�����5%:��bJMX h�bbd```b``Y"[email protected]$S����c��5`�?Xe#�=D���� �y+�d�&��"k�*��"�`����))��� 3119 0 obj <>stream %PDF-1.6 %���� �ʕ��x-�� g���� ծ��M����+�B7�?D��$8G��k�D"�C���Re��P�*�����oT�s�&�j�Dt�P5#�k�^�y�:�ER��J"��M���H�W���g�U���Q����h�`N��� �jb�}��,��-�x�R+����^�� U��a�x8��69��!�ĉ1��z|G���?�~� For the determination of equilibrium solubility the chapter describes the Saturation Shake-Flask Method. Soluble in solutions of potassium and Alanine: White, odorless crystals or crystalline powder, sodium hydroxides; very slightly soluble in water and in al- having a slightly sweet taste. Freely soluble in water; slightlycohol; practically insoluble in chloroform and in ether. x�b```�l����cb��@ޑ6e ��� S}]�Z�-�[email protected]�yT�L�3ҙ�^�v�03�yp�q�b� Z�Na;0Wt4�vt04�D I0b��`�`�h�0d�� �T,���ړ_p�����w�y�,��hH���e`dNx�����[���'�S��f`�s� 3� endstream endobj 235 0 obj <>/Metadata 25 0 R/Pages 232 0 R/PageLayout/OneColumn/StructTreeRoot 45 0 R/Type/Catalog>> endobj 236 0 obj <>/ColorSpace<>/Font<>/ExtGState<>>>/Type/Page>> endobj 237 0 obj <>stream The “description” and “solubility” statements pertaining to an article (formerly included in the individual monograph) are general in nature. Description and Solubility Nonmonograph tests and acceptance criteria suitable for Only where a quantitative solubility test is given in a detecting and controlling impurities that may result from a monograph and is designated as such is it a test for purity.change in the processing methods or that may be intro- A monograph may include information regarding the arti-duced from external sources should … h�b```��l�>B �� x��Y�n7�>&(��\ 0`˹�� V��6����!m���;3��ZK��M�0�h�!��ó�]i�L�D �a�Cc��ZDŽV�홰 )�� �0���x}.^��������k��O����f>m�[email protected]��~�2��B��Kp���U�ׯ���J��Wm��z�j+� Description and Relative Solubility of USP and NF Articles. One of the workshop outcomes was a decision by participants that the content of the new general chapter would focus on species-appropriate descriptions of conditions for testing in vitro drug For the determination of apparent s…