348 Introduction e water-solid interaction(s) among pharmaceuticals is of great interest in drug development process. [1–3] A pharmaceutically active or inactive ingredient encom- passes varied levels of humidity during different stages of product development, that is to say, during synthesis, storage and analysis of that ingredient, or during various unit operations of drug product development like, spray or freeze drying, wet milling, granulation, etc. e ad-/ ab-sorption of water molecules by a pharmaceutical solid can largely affect its performance with regard to stability, flow, wetness, dissolution, compressibility or compactability, etc. [4–13] Further, varied handling or stor- age conditions can alter the properties of materials with regard to their equilibrium moisture content (EMC). Hygroscopicity is a terminology commonly used for describing the interaction of a material with water. [14] It is often used for characterizing a material as such, [15] or for making a selection among various polymorphs of a drug molecule, [16–20] or for selecting salt-formers during initial salt screening attempts. [21–24] Based on its extent of interaction with water, a material can be classified as non-hygroscopic or hygroscopic. Hygroscopicity of a sample can be determined by a multitude of analytical methods. [25] e earliest reported and widely practiced method for hygroscopicity deter- mination or classification was the one proposed by Callahan and co-workers. [26] is method is referred to as the “conventional method” herein. It is based upon the determination of EMC of samples equilibrated at partic- ular relative humidity (RH) using saturated salt solutions in the well of the desiccators (Table 1). is method for hygroscopicity classification of phar- maceuticals is widely practiced as such, [27] or with some modifications. [28] However, this method suffers from RESEARCH ARTICLE Efficient throughput method for hygroscopicity classification of active and inactive pharmaceutical ingredients by water vapor sorption analysis Vasudha Murikipudi, Piyush Gupta, and Vaibhav Sihorkar Pharmaceutical Development, Aurigene Discovery Technologies Limited, Bollaram Road, Miyapur, Hyderabad, Andhra Pradesh, India Abstract The conventional method of hygroscopicity determination proposed by Callahan and co-workers utilizes more sample and time, may not be precise in all the cases, and is a relatively broader classification system. The method of indicating degree of hygroscopicity as per European Pharmacopoeia considers equilibration of sample for 24 hours under single humidity condition and may not necessarily ensure equilibration in all the cases. Additionally, both these methods do not provide information on solid state changes occurring within the sample during the course of experiment. This research work envisages an efficient throughput method for hygroscopicity determination, and validates it with active and inactive pharmaceutical ingredients using sorption analysis. Further, this method has been performed under optimal equilibration conditions, in a throughput manner (consuming less sample and time), with additional information on solid state changes occurring within the experimental conditions. This throughput method would be a valuable tool for hygroscopicity assessment of new chemical entities, during drug development in particular, and across all pharmaceutical materials in general. Keywords: Hygroscopicity, water vapor sorption, adsorption, desorption, pre-formulation Address for Correspondence: Vaibhav Sihorkar, Pharmaceutical Development, Aurigene Discovery Technologies Limited, Bollaram Road, Miyapur, Hyderabad, Andhra Pradesh 500 049, India. Tel: +91 40 4465 7777. Fax: +91 40 4465 7438. E-mail: vaibhav_s@aurigene.com; IP Clearance No. H-01/1025/2010. (Received 12 April 2011; revised 17 August 2011; accepted 18 August 2011) Pharmaceutical Development and Technology, 2013; 18(2): 348–358 © 2013 Informa Healthcare USA, Inc. ISSN 1083-7450 print/ISSN 1097-9867 online DOI: 10.3109/10837450.2011.618947 Pharmaceutical Development and Technology Downloaded from informahealthcare.com by Novartis Pharma on 01/14/13 For personal use only.