Thermotropic liquid crystalline drugs

Abstract

Crystalline solids are characterized by long-range positional and orientational order in three dimensions, whereas amorphous liquids lack long-range order in any dimension. Liquid crystals (mesophases) show structural, mechanical and optical properties intermediate to those of crystalline solids and the amorphous, liquid state of matter. There are two principle types of liquid crystals: thermotropic liquid crystals (TLCs) and lyotropic liquid crystals (LLCs). TLCs can be formed by heating a crystalline solid or by cooling an isotropic melt of a TLC-forming molecule (mesogen). In the first part of this review the types of liquid crystals are defined and classified and the structural properties of mesogens are explained. In the second part, ten case studies of thermotropic mesomorphous drugs and pharmaceutically relevant molecules (arsphenamine, nafoxidine hydrochloride, L-660711, palmitoyl propranolol hydrochloride, penbutolol sulfate, itraconazole hydrochloride, fenoprofen sodium, fenoprofen calcium, ciclosporin and cholesteryl esters) are presented and their thermotropic mesomorphism is described. The review closes with a brief discussion of the unusual properties of drug mesophases and a potential use of drugs and excipients in this fourth state of matter.

Crystalline, liquid crystalline, and isotropic phases of sodium deoxycholate in water

“…It is increasingly recognized, however, that many pharmaceutical systems form crystalline mesophase or liquid crystalline (LC) state (in which some degree of molecular disorder/freedom is retained) and have intermediate order between highly ordered crystalline and disordered amorphous materials. [1][2][3] The study of phase relationships in systems with crystalline mesophases represents significant challenges because of multiple LC phases that often coexist, and transition from one to another in narrow temperature/composition regions. As a result, many phase diagrams reported for such mesomorphic systems (e.g., phospholipids) are represented as "empirical" phase diagrams, without considering underlying thermodynamic rules (i.e., the phase rule, 4 the boundary rule, 5 and the boundary-curvature rule 6 ).…”

General Trends in the Desolvation Behavior of Calcium Salts

“…There are few articles in the pharmaceutical literature that discuss thermotropic mesophases (12,13), as well as few articles that are devoted to the study of calcium salts.…”

“…However, very few articles discussed the physical and chemical properties of liquid crystalline drugs (12,13). Patterson et al can have a profound influence on physical stability and that liquid crystalline tobramycin freebase/sulfate was more stable and less sensitive to moisture than its amorphous counterpart (9).…”

Innovation in Drug Carriers: Supercooled Smectic Nanoparticles

“…Lyotropic mesomorphism is utilized in the area of pharmaceutics [8,9] whereas thermotropic mesomorphism has been described for some drug substances [10]. Thermotropic mesophases which are solvent free and hence lipophilic in nature have similarities with the dispersed phase of colloidal lipid emulsions.…”