Olanzapine Solvates

Abstract

Olanzapine was crystallized from 12 organic solvents alone or in mixture, by cooling in the freezer, by slow evaporation of the solvent, or by suspending olanzapine powder for some time in the solvent. All the samples thus obtained were examined by thermal analysis (differential scanning calorimetry-DSC and thermogravimetry-TG) to certify the formation of a solvate, the presence of polymorph (form 1 or 2) in the desolvated olanzapine, comparing the different profile of the thermograms, and to calculate the stoichiometry of the possible solvate. According to the DSC thermogram, the solvents can be divided into four classes: those that do not form solvates and leave olanzapine form 1 (ethyl acetate, toluene, diethyl ether, and acetone); those that form solvate and leave form 1 of olanzapine after desolvation (methanol, 1- and 2-propanol); those that after desolvation of the solvate show a polymorph transition in the thermogram indicating the presence of form 2 of olanzapine (ethanol); other solvents (tetrahydrofuran, chloroform, acetonitrile) give solvate thermograms, where this last thermal trace is only poorly evident. With few exceptions, each solvent forms solvate both when pure and in mixture (10%, v/v, in ethyl acetate). Methanol monosolvate displays complex thermogram and thermogravimetric desolvation profiles, depending on the crystallization experimental conditions, used to prepare the solvates. Dichloromethane solvate was found by X-ray diffraction analysis to be amorphous and, on heating during DSC analysis, allowed the crystallization of both form 1 and 2, with different weight ratio, according to the experimental conditions of the solvate preparation.

Design of Olanzapine/Lutrol Solid Dispersions of Improved Stability and Performances

“…All the carriers considered here are low melting materials, suitable for the melting method of the solid dispersion preparation that avoids the use of organic solvents and the problems accompanying their use in this process [ 16 ].…”

“…The solubility parameter δ cannot be found in the recent literature for olanzapine, but it could be simply determined using the method of the solubility peak. The problem of the formation of solvate with most solvents limits the choice of solvents, enabling measurements of solubility for unsolvated olanzapine, that is the form used in the present work: olanzapine was found to crystallize unsolvated from acetone, ethyl acetate, toluene, and ethyl ether [ 16 ], whose solubility parameters are 9.77, 9.10, 8.91, and 7.62 (MPa) 1/2 respectively [ 19 ]. As these solvents display very close δ values, it could be estimated that the δ value for olanzapine, when determined by the solubility peak method, should fall in the range 9.77–7.62 (MPa) 1/2 , which represents a fairly low value.…”

Mechanochemical Synthesis of Olanzapine Salts and Their Hydration Stability Study Using Powder X-ray Diffraction

“…Olanzapine is a dibasic molecule with p K a 7.37 and 4.69 for piperazine and diazapine nitrogens, respectively. Along with polymorphic guest-free forms, − a large number of OLN solvates, , salts, , and cocrystals , were reported in the literature including a recent report from our group . In a recent work, Florence and co-workers investigated the hydrate formation of OLN with the aid of atomic force microscopic (AFM) analysis. , Analysis of available crystal structures revealed that all the hydrated forms (hemi-, mono-, and dihydrate) contain O–H···N hydrogen bond between water and piperazine nitrogen of OLN.…”

First-line antituberculosis drug, pyrazinamide, its pharmaceutically relevant cocrystals and a salt

“…Cocrystallization is quite new compared with other solid-state techniques (Blagden et al, 2007), viz. preparation of polymorphs (Hilfiker, 2006;Haleblian & McCrone, 1969;Brittain, 2009;Lee, 2014), molecular salts (Stahl & Wermuth, 2008;Berge et al, 1977;Wouters & Qué ré, 2011), amorphous formulations (Yu, 2001;Babu & Nangia, 2011) or solvates and hydrates (Griesser, 2006;Cavallari et al, 2013). The major advantage of cocrystallization compared with other solid-state techniques is that no ionisable groups are required either for the drug or for the coformer.…”