Crystal Engineering to Design of Solids: From Single to Multicomponent Organic Materials

Abstract

: Pharmaceutical materials which comprise drugs and excipients are mainly organic molecules. These materials frequently exhibit physicochemical properties that can impact formulation, manufacturing and packing processes as well as product performance and safety. In this context, crystal engineering (CE) has intensively grown in recent years as a strategy to reinvent bioactive molecules with well-known and approved pharmacological effects. It aims to improve their physicochemical properties without affecting the molecules’ intrinsic characteristics or compromising their stability. CE is based on molecular recognition involving non-covalent interactions, which in organic materials, are responsible for the regular arrangement of molecules in the crystal lattice. Modern CE encompasses any manipulation that results in an alteration of the crystal packing as well as methods that cause crystal lattice disruption, crystal size reduction or a combination of them. Nowadays, cocrystallization has been the most explore strategy to improve solubility, dissolution rate and bioavailability. However, its combinatorial nature involving two or more small organic molecules, and the use of diverse crystallization processes increase the possible outcomes. As a result, numerous organic materials can be obtained as well as several physicochemical and mechanical properties can be improved. Therefore, this review will focus on novel organic solids obtained when CE is applied including crystalline and amorphous, single and multicomponent as well as nanosized ones, that have contributed to improving not only solubility, dissolution rate, bioavailability permeability but also, chemical and physical stability and mechanical properties.

Interaction and Compatibility Studies in the Development of Olmesartan Medoxomil and Hydrochlorothiazide Formulations under a Real Manufacturing Process

“…It is well known that industrial manufacturing processes like drying, milling, micronization, wet granulation, lyophilization, and compaction can cause polymorphic transformations and the unexpected appearance of new crystalline phases [25,26]. Those procedures have been intentionally applied to achieve a physicochemical property modification based on the crystal engineering approach in the light of all possible manipulations of altering crystal packing, to disrupt crystal lattices, and/or reduce the size of the crystal [27]. A search in the literature as well as in the Cambridge Structural Database (CSD) was performed for both drugs.…”

Use of nanosystems to improve the anticancer effects of curcumin

“…Nanococrystals, on the other hand, are a combination of two different approaches that include cocrystal preparation and subsequently the nanonization of the obtained cocrystal [ 54 ]. The resulting material combines the advantages of cocrystals and nanoscale size to considerably increase solubility, dissolution rate, and bioavailability of the molecules of interest [ 55 ]. In addition, as the second molecule in the crystal lattice can also be a bioactive one, their expected effect when used as therapeutic agents can be improved due to their synergic action.…”

Crystal Forms of the Antihypertensive Drug Irbesartan: A Crystallographic, Spectroscopic, and Hirshfeld Surface Analysis Investigation

“…The crystallization process to obtain different crystal forms has been extensively explored as a strategy to improve the limited bioavailability imposed by poorly water-soluble drugs. 1 − 4 Although the influence of the process on the properties of dosage forms and products is well-documented, however, the effects of some variables are not well-understood. 5 − 7 In this scenario, it is noteworthy that the crystallization process has evolved from an empirical to a theory-based science and has allowed the launching of safer products.…”

“…The crystallization process to obtain different crystal forms has been extensively explored as a strategy to improve the limited bioavailability imposed by poorly water-soluble drugs. − Although the influence of the process on the properties of dosage forms and products is well-documented, however, the effects of some variables are not well-understood. − In this scenario, it is noteworthy that the crystallization process has evolved from an empirical to a theory-based science and has allowed the launching of safer products . Furthermore, this knowledge has been applied to controlling the factors that impact phase transformations in the solid-state. , Therefore, the effects of crystallization variables need to be thoroughly investigated for each drug, specifically by experimental methods.…”