1123 Ther. Deliv. (2014) 5(10), 1123–1142 ISSN 2041-5990 Therapeutic Delivery Review part of 10.4155/TDE.14.68 © 2014 Future Science Ltd The active pharmaceutical ingredient (API) of a dosage form is affected by number of mechanical and environmental factors which have a tendency to alter its crystalline state. Polymorphic transitions have been observed to occur during various unit operations like granulation, milling and compression. Forces of pressure, shear and temperature have an ability to induce alterations in crystal habit. A conversion in polymorphic form during a unit operation is very likely to affect the handling of API in the subsequent unit operation. Transitions have also been observed during storage of formulations where the relative humidity and temperature play a major role. An increase in temperature during storage can dehydrate or desolvate the crystal and hence produce crystal defects, whilst, high humidity conditions produce higher molecular mobility leading to either crystallization of API or alteration of its crystalline form. Background The phenomenon of a solid to crystallize in forms having different arrangements of mol- ecules in the crystal is referred to as polymor- phism. Polymorphism comes from the Greek word ‘Polus’ meaning many and ‘morphs’ meaning shape. A substance may exist in different polymorphic forms due to differ- ences in crystal lattice structure. This even- tually results in molecules having different arrangements in the unit cell of the crystal. It is important to recognize the fact that different polymorphs or its solvates and hydrates, (pseudopolymorphs) may or may not manifest different shapes (crystal habits). Difference in crystal structure may result in signifcantly different physiochemical proper- ties, absorption rates and sometimes, different pharmacological activities. The accompany- ing changes in crystal habit of polymorphs or pseudopolymorphs make the situation even more challenging due to the ability of different crystal shapes to infuence porosity [1] , powder fow [2,3] , packing, compaction [4,5] and dissolution of solid dosage forms [6] as well as syringability and sedimentation rate of suspension dosage forms [7,8] . History remembers the defeat of Napolean Bonaparte, the French military and politi- cal leader in the chilling winter of 1812 in Moscow. His defeat was attributed to poly- morphic change of stable white tin to grey tin below 18°C that resulted in crumbling of dress buttons and spoilage of canned food. Pharmaceuticals, especially the active phar- maceutical ingredients (APIs), are character- ized for their polymorphic state right at the initial stage of their discovery. However, the possibility of encountering new polymor- phic forms of APIs during their processing into dosage forms cannot be ruled out due to the infuence of different types of stress that are inficted on them during subsequent formulation phase. A precise understanding of the effect of various process and stress conditions on APIs and their after effects on subsequent processes and the fnal prod- uct helps us in designing process param- eters providing or maintaining the desired polymorphic form. Despite wide recognition of the infuence of polymorphic state of APIs on physicochemical properties and performance of dosage forms, these changes often skip the attention of for- Understanding pharmaceutical polymorphic transformations I: influence of process variables and storage conditions Jatin Sood 1 , Bharti Sapra 1 , Sameer Bhandari 1 , Manish Jindal 2 & Ashok K Tiwary* ,1 1 Pharmaceutics Division, Department of Pharmaceutical Sciences & Drug Research, Punjabi University, Patiala 147 002, India 2 Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India *Author for correspondence: aktiwary2@rediffmail.com For reprint orders, please contact reprints@future-science.com