2018
DOI: 10.1039/c8ce00663f
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The heterogeneous crystallization of a novel solvate of clozapine base in the presence of excipients

Abstract: This paper reports the heterogeneous crystallization of a novel solvate of clozapine base in the presence of excipients.

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Cited by 13 publications
(15 citation statements)
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“…Upon gentle heating or vacuum drying of the harmine phenolate, the macromorphology of the crystal is preserved (Figure 5 The production of a porous API through the evaporation of solvent has been demonstrated previously for clozapine to which the porous structure increased the dissolution rate 5-fold. 36 Both carbamazepine and verapamil hydrochloride show no crystallisation or melting events at any ratio except an exotherm followed directly by and endotherm in the carbamazepine system at 10:1. Both systems display a Tg on both cooling and warming, which moves systematically towards lower temperatures with higher ratios.…”
Section: Thermal Analysis and Applicabilitymentioning
confidence: 94%
“…Upon gentle heating or vacuum drying of the harmine phenolate, the macromorphology of the crystal is preserved (Figure 5 The production of a porous API through the evaporation of solvent has been demonstrated previously for clozapine to which the porous structure increased the dissolution rate 5-fold. 36 Both carbamazepine and verapamil hydrochloride show no crystallisation or melting events at any ratio except an exotherm followed directly by and endotherm in the carbamazepine system at 10:1. Both systems display a Tg on both cooling and warming, which moves systematically towards lower temperatures with higher ratios.…”
Section: Thermal Analysis and Applicabilitymentioning
confidence: 94%
“…The kinetic and the thermodynamic parameters were derived using Equation 3published by Kashchiev et al 61 and used by the authors in the past. 14,42 𝐽(𝑆) = 𝐴 𝑆 exp ( -𝐵/𝑙𝑛 2 𝑆)…”
Section: Figure 6: (A) and (B) Plot Of 'Ln(j/s) Or Ln(j * /S)' Against (1/(t 3 Ln 2 S)) × 10 6 Which Illustrates The Dependence Of Nucleamentioning
confidence: 99%
“…This is consistent with their previous findings on the nucleation of clozapinemethanol solvate in the presence of MCC, confirming that the pre-exponential factor is the major contributing factor to heterogeneous nucleation. 42 Glycine and diglycine were selected as molecules of interest for this work. The reason for this is that glycine is the simplest and most studied amino acid, consisting of a non-heavy hydrogen side chain, which eliminates the need to consider the effect of the side chain of the amino acid when analysing the effect of the heterosurface.…”
Section: Introductionmentioning
confidence: 99%
“…In the free base (Fillers & Hawkinson, 1982) this angle is 67.3 [unfortunately, the atomic coordinates retrieved from the CSD (Groom et al, 2016) have no s.u. values] and in the monohydrate (CSD refcode DEHBUP; the publication cited in the CSD could not be traced) and the methanol solvate (Verma et al, 2018), the corresponding angles are 63.4 and 56.1 , respectively. In the 1:1 salt formed with 3,5-dinitrobenzoic acid (II), this angle is 62.21 (11) (Kaur et al, 2015), fairly similar to the values of 60.97 (9) and 59.07 (16) in the 1:1 salts formed with maleic and 2-hydroxybenzoic acids, respectively (Kaur et al, 2015).…”
Section: Figurementioning
confidence: 99%
“…There are no hydrogen bonds in the structure of clozapine itself (Fillers & Hawkinson, 1982), but in the monohydrate (DEHBUP), a combination of one N-HÁ Á ÁO hydrogen bond and two O-HÁ Á ÁN hydrogen bonds links the components into a chain of rings. In the methanol solvate of clozapine (Verma et al, 2018), the components are linked by an O-HÁ Á ÁN hydrogen bond, but with no further aggregation. In the hydrogenmaleate and 2-hydroxybenzoate salts, multiple hydrogen bonds generate sheets and a three-dimensional supramolecular network, respectively (Kaur et al, 2015), while in the di(hydrobromide) salt, the ions are linked into chains by N-HÁ Á ÁBr hydrogen bonds (Fillers & Hawkinson, 1982).…”
Section: Figurementioning
confidence: 99%