Medical brain notes 14

  INTRODUCTION During the past four decades a plethora of newer complex organic medicinal compounds have taken cognizance in the therapeutic armamentarium. Evidently, these compounds posed  two  vital problems of quality control, both in pure and dosage forms by virtue of their inherent characteristics, namely :   ( a ) poor solubility, and   ( b ) weak reactivity in aqueous medium.   Initially, the above  two  problems were usually circumvented in the following manner :   Example 1 :  Amine salts —It is first changed to the water-soluble free base, extracted with an appro-priate organic solvent and treated with an excess volume of standard acid ; subsequently, the solvent was evaporated, and the remaining acid determined with a standard base.   Example 2 :  Sodium salts —It is first acidified to release the water-insoluble organic acid, extracted   with a suitable organic solvent, the solvent was removed and the residue w...

  THEORY The concepts of the Lowry-Bronsted theory may explain the various reactions that take place during many non-aqueous titrations. Thus, an  acid  is a  proton  donor and a  base  is a  proton acceptor . Therefore, when an acid HA undergoes dissociation it gives rise to a proton and the conjugate base A of the acid : In other words, the liberated base A shall unite with a proton to give the corresponding conjugate acid HA of the base A because every base has its conjugate acid and  vice versa.   Hence, from the above definitions it may be implied that :   ( a )  an acid :  could be either an electrically neutral molecule  e.g. , HNO 3  ; or a negatively charged anion  e.g. , HSO 4 –  ; or a positively charged cation  e.g. , C 6 H 5 NH 2 +  , H 3 O ;   ( b )  a base :  could be either an electrically neutral molecule  e.g. , C 6 H 5 NH 2  ; or an anion  e.g.,...

  METHODOLOGY For non-aqueous titrations, the following  four  steps are usually taken into consideration, namely :   ( i ) Preparation of 0.1 N Perchloric acid,   ( ii ) Standardization of 0.1 N Perchloric Acid,   ( iii ) Choice of Indicators, and   ( iv ) Effect of Temperature on Assays.   1. PREPARATION OF 0.1 N PERCHLORIC ACID   Materials Required :  8.5 ml of perchloric acid (70.0 to 72.0%) ; 1 Litre of glacial acetic acid ; 30 ml   of acetic anhydride. Procedure :  Gradually mix 8.5 ml of perchloric acid to 900 ml of glacial acetic acid with vigorous   and continuous stirring. Now add 30 ml acetic anhydride and make up the volume to 1 litre with glacial acetic acid and allow to stand for 24 hours before use.   The acetic anhydride reacts with the water (approx. 30%) in perchloric acid and some traces in glacial acetic acid thereby making the resulting mixture practically anhydrous. Thus, we have : Precautions :...

  ASSAY BY NON-AQUEOUS TITRATIONS Assays of various pharmaceutical substances either in pure form or in dosage form may be assayed successfully by non-aqueous titrations. For the sake of convenience these typical titrations can be catego-rized into  two  broad groups, namely :   ( a )  Acidimetry in Non-aqueous Titrations— It can be further sub-divided into  two  heads, namely :   ( i ) Titration of primary, secondary and tertiary amines, and   ( ii ) Titration of halogen acid salts of bases.   (b) Alkalimetry in Non-aqueous Titrations — i.e. , titration of acidic substances.   1. ACIDIMETRY IN NON-AQUEOUS TITRATIONS   In order to perform feasible titrations of weak bases, the solvent system should be selected specifically in such a fashion so as to eliminate as far as possible the competing reaction of water for the proton besides enhancing the strength of the basic species.   1.1. Titration of primary, secondary and tert...