Characterisation and evaluation of pharmaceutical solvates of Atorvastatin calcium by thermoanalytical and spectroscopic studies

Abstract

BackgroundAtorvastatin calcium (ATC), an anti-lipid biopharmaceutical class II drug, is widely prescribed as a cholesterol-lowering agent and is presently the world’s best-selling medicine. A large number of crystalline forms of ATC have been published in patents. A variety of solid forms may give rise to different physical properties. Therefore, the discovery of new forms of this unusual molecule, ATC, may still provide an opportunity for further improvement of advantageous properties.ResultsIn the present work, eight new solvates (Solvate I-VIII) have been discovered by recrystallization method. Thermal behaviour of ATC and its solvates studied by DSC and TGA indicate similar pattern suggesting similar mode of entrapment of solvent molecules. The type of solvent present in the crystal lattice of the solvates is identified by GC-MS analysis and the stoichiometric ratio of the solvents is confirmed by 1HNMR. The high positive value of binding energy determined from thermochemical parameters indicates deep inclusion of the solvent molecules into the host cavity. The XRPD patterns point towards the differences in their crystallanity, however, after desolvation solvate II, III, IV, V and VIII transform to isostructral amorphous desolvated solvates. The order of crystallinity was confirmed by solution calorimetric technique as the enthalpy of solution is an indirect measure of lattice energy. All the solvates behaved endothermically following the order solvate-VIII (1-butanol solvate) < solvate-I (isoproplyate) < solvate-V (methanol solvate) < solvate-III (ethonalate) < solvate-VI (acetone ethanol solvate) < solvate-IV (t-butanol solvate) < solvate-II (THF solvate) < solvate-VII (mixed hemi-ethanol hydrate). The positive value of the heat capacity of the solvate formation provides information about the state of solvent molecules in the host lattice. The solvents molecules incorporated in the crystal lattice induced local chemical environment changes in the drug molecules which are observed in 13CP/MAS NMR spectral changes.ConclusionsAqueous solubility of solvate-VIII was found to be maximum, however, solvate-I and VIII showed better reduction in total cholesterol and triglyceride levels as compared to atorvastatin against triton-induced dyslipidemia.

Polymorph Impact on the Bioavailability and Stability of Poorly Soluble Drugs

“…At least 60 polymorphic forms/solvates/hydrates have been patented [99][100][101] and several pharmaceutical companies are developing or have developed generic drug formulations based on different atorvastatin calcium polymorphs.…”

Crystal structures and properties of two hydrated conglomerate forms of the heart-rate-lowering agent ivabradine hydrochloride

“…The quantitative estimate of the stability of both forms can be established by determining the binding energies (Chadha et al, 2009(Chadha et al, , 2010(Chadha et al, , 2012Caira et al, 2007) from the equation:…”

Preparation and Characterization of a Novel Cocrystal of Atorvastatin Calcium with Succinic Acid Coformer

“…Patent protection for atorvastatin calcium has expired in 2011, so the research to modify the physicochemical properties of atorvastatin calcium is an exciting opportunity in the field of pharmaceutical research. The most common ways to modify the atorvastatin calcium is by the formation of new polymorphs, solvates and crystalline forms [4][5].The formation of a new form from atorvastatin calcium is known to improve the solubility [6], dissolution rate [7] and stability [8].…”