Polymorphism: Fundamentals and Applications

Abstract

Polymorphism is the ability of a compound to exist in more than one crystalline modification through different arrangements of the molecules in the solid state. Polymorphism has enormous economic and practical implications because of its ability to alter the physical and chemical properties of active pharmaceutical ingredients. The identification and complete characterization of polymorphs in the early stages of drug development is a necessary step to avoid serious financial setback in drug development and manufacturing. Thanks to new techniques such as high‐throughput screening and advances in analytical methods it has become possible to explore solid‐form diversity even with a small amount of sample in a short time. This chapter attempts to provide an overview of the fundamentals of polymorphism and the factors that control the crystallization of polymorphs. The potential implications of polymorphism in the pharmaceutical industry are highlighted with some recent examples.

Selective crystallisation of carbamazepine polymorphs on surfaces with differing properties

“…12,13,34 The polymorphic outcome is affected by crystallisation conditions including concentration, the supersaturation range, temperature, solvent, the presence of additives, nucleating surfaces and several other external factors. 35,36 In this work, glass and PTFE surfaces, which have lower surface energies than tin in this work, induced a high percentage of occurrence of Form II, which is consistent with the literature that the cyano surface induces more Form II than mercapto and fluoro surfaces, which have more than two times higher surface energy than the cyano surface. 13 It is noticed that when 2 or 8 inserts of tin were added, if both Form II and Form III crystals were observed in the solution, nearly all the crystals on the tin surfaces would be Form III in the experiments, which indicates that, unlike glass and PTFE surfaces, tin surfaces prefer to generate Form III carbamazepine.…”

Recurrent Supramolecular Motifs in a Series of Acid–Base Adducts Based on Pyridine-2,5-Dicarboxylic Acid N-Oxide and Organic Bases: Inter- and Intramolecular Hydrogen Bonding

“…At least half of the marketed active pharmaceutical ingredients (APIs) are administered as salts. In general, a salt is formed via proton transfer from an acid to a base, leading to the formation of a conjugate acid (protonated base) and conjugate base (deprotonated acid). − Over the past decade, Mirzaei et al have focused on the synthesis and structural characterization of novel supramolecular proton-transferred compounds − and coordination complexes , based on derivatives of pyridinedicarboxylic acids, owing to their remarkable applications such as anticancer properties, anti-HIV agent, gas adsorbent, etc. − …”

Three new hydrochlorothiazide cocrystals: Structural analyses and solubility studies

“…HCT is a poorly soluble drug (0.7 g/L) 1 . Poor aqueous solubility not only limits its 303 dissolution and absorption but also challenges its pharmaceutical development.…”

“…1 HCT and cocrystal former in a definite stoichiometric ratio were subjected to grinding using 132 an agate mortar and pestle for about 6 to 8 min with the addition of few drops of methanol.…”