Solid‐state characterization of novel active pharmaceutical ingredients: Cocrystal of a salbutamol hemiadipate salt with adipic acid (2:1:1) and salbutamol hemisuccinate salt

Paluch, Krzysztof J.; Tajber, Lidia; Elcoate, Curtis J.; Corrigan, Owen I.; Lawrence, Simon E.; Healy, Anne Marie

doi:10.1002/jps.22569

Cited by 34 publications

(52 citation statements)

References 32 publications

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“…We previously reported full deprotonation of succinic acid in salbutamol succinate, with C-O bond distances of 1.274(1) and 1.253(2) Ǻ. 7 In the second carboxylic group of S, which is protonated, the interatomic distance for O6-C22 is 1.211(2) Ǻ and C22-O7 is 1.324(2) Ǻ.…”

Section: Structural Analysis Of Chs-i and Cs-imentioning

confidence: 98%

“…7 The Eppendorf vials were then hermetically sealed, placed horizontally in a water bath at 25 ºC and shaken at 100 cpm.…”

Section: Equilibrium Solubility Studiesmentioning

confidence: 99%

“…33 The content of succinic acid was determined using the conditions previously described. 7 Briefly, a Shimadzu 10Avp HPLC system (Tokyo, Japan) was employed and the separation was done at room temperature. For ciprofloxacin the analytical column used was a C18 ( linear gradient from 0% to 50% B over 7 min, and then a linear gradient from 50% to 100% B over 1 min; this composition was maintained for 7 min.…”

Section: High Performance Liquid Chromatography (Hplc)mentioning

confidence: 99%

“…6 Recently, we reported on the ability of another amphoteric molecule, salbutamol, to form a salt with succinic acid or a cocrystal of salbutamol adipate salt with adipic acid. 7 All of the above examples of counterions include organic acids with more than one carboxylic group, potentially presenting the possibility of the formation of salts with multiple stoichiometries. While, in theory, it is possible to predict whether multiple stoichiometries are likely to form, based on the chemical structure of the drug and counterion, it is not yet possible to predict if salts with different stoichiometries will crystallise.…”

Section: Introductionmentioning

confidence: 99%

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Formation and Physicochemical Properties of Crystalline and Amorphous Salts with Different Stoichiometries Formed between Ciprofloxacin and Succinic Acid

Paluch¹,

McCabe²,

Müller‐Bunz

et al. 2013

Mol. Pharmaceutics

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Multi-ionisable compounds, such as dicarboxylic acids, offer the possibility of forming salts of drugs with multiple stoichiometries. Attempts to crystallise ciprofloxacin, a poorly water soluble, amphoteric molecule with succinic acid (S) resulted in isolation of ciprofloxacin hemisuccinate (1:1) trihydrate (CHS-I) and ciprofloxacin succinate (2:1) tetrahydrate (CS-I). Anhydrous ciprofloxacin hemisuccinate (CHS-II) and anhydrous ciprofloxacin succinate (CS-II) were also obtained. It was also possible to obtain stoichiometrically equivalent amorphous salt forms, CHS-III and CS-III, by spray drying and milling, respectively, of the drug and acid. Anhydrous CHS and CS had melting points at ~215 and ~228 °C, while the glass transition temperatures of CHS-III and CS-III were ~101 and ~79 °C, respectively. Dynamic solubility studies revealed the metastable nature of CS-I in aqueous media, resulting in a transformation of CS-I to a mix of CHS-I and ciprofloxacin 1:3.7 hydrate, consistent with the phase diagram. CS-III was observed to dissolve non-congruently leading to high and sustainable drug solution concentrations in water at 25 and 37 ºC, with the ciprofloxacin concentration of 58.8±1.18 mg/ml after 1 hour of the experiment at 37 ºC. This work shows that crystalline salts with multiple stoichiometries and amorphous salts have diverse pharmaceutically-relevant properties, including molecular, solid state and solubility characteristics.

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Section: Structural Analysis Of Chs-i and Cs-imentioning

confidence: 98%

“…7 The Eppendorf vials were then hermetically sealed, placed horizontally in a water bath at 25 ºC and shaken at 100 cpm.…”

Section: Equilibrium Solubility Studiesmentioning

confidence: 99%

Section: High Performance Liquid Chromatography (Hplc)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Formation and Physicochemical Properties of Crystalline and Amorphous Salts with Different Stoichiometries Formed between Ciprofloxacin and Succinic Acid

Paluch¹,

McCabe²,

Müller‐Bunz

et al. 2013

Mol. Pharmaceutics

Self Cite

View full text Add to dashboard Cite

show abstract

“…A number of cocrystals of APIs with different co-formers formed by different methods have been reported and it was shown that the solid-state interactions between the two compounds are mainly based on hydrogen bonds Childs et al, 2004;Lu and Rohani, 2009;Padrela et al, 2009;Paluch et al, 2011;Trask et al, 2005;Wenger and Bernstein, 2008). We have previously shown that the sulfoxide (S=O) functionality, common in a significant number of APIs, is a potent hydrogen bonding acceptor and forms cocrystals in association with a wide variety of amino (NH) functional groups (Eccles et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Characterisation, solubility and intrinsic dissolution behaviour of benzamide: dibenzyl sulfoxide cocrystal

Grossjohann

Eccles

Maguire

et al. 2012

International Journal of Pharmaceutics

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This study examined the 1:1 cocrystal benzamide: dibenzyl sulfoxide, comprising the poorly water soluble dibenzyl sulfoxide (DBSO) and the more soluble benzamide (BA), to establish if this cocrystal shows advantages in terms of solubility and dissolution in comparison to its pure components and to a physical mixture. Solubility studies were performed by measuring DBSO solubility as a function of BA concentration, and a ternary phase diagram was constructed. Dissolution was examined through intrinsic dissolution studies. Solid-state characterisation was carried out by powder X-ray diffraction (PXRD), energy-dispersive X-ray diffraction (EDX), infra-red spectroscopy (ATR-FTIR) and thermal analysis. DBSO solubility was increased by means of complexation with BA. For the cocrystal, the solubility of both components was decreased in comparison to pure components. The cocrystal was identified as metastable and incongruently saturating. Dissolution studies revealed that dissolution of DBSO from the cocrystal was not enhanced in comparison to the pure compound or a physical mix, while BA release was retarded and followed square root of time kinetics. At the disk surface a layer of DBSO was found. The extent of complexation in solution can change the stability of the complex substantially. Incongruent solubility and dissolution behaviour of a cocrystal can result in no enhancement in the dissolution of the less soluble component and retardation of release of the more soluble component

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Study of supramolecular frameworks having aliphatic dicarboxylic acids, N,N′-bis(salicyl)ethylenediamine and N,N′-bis(salicyl)butylenediamine

Goel

Kumar

2014

Journal of Molecular Structure

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Solid‐state characterization of novel active pharmaceutical ingredients: Cocrystal of a salbutamol hemiadipate salt with adipic acid (2:1:1) and salbutamol hemisuccinate salt

Cited by 34 publications

References 32 publications

Formation and Physicochemical Properties of Crystalline and Amorphous Salts with Different Stoichiometries Formed between Ciprofloxacin and Succinic Acid

Formation and Physicochemical Properties of Crystalline and Amorphous Salts with Different Stoichiometries Formed between Ciprofloxacin and Succinic Acid

Characterisation, solubility and intrinsic dissolution behaviour of benzamide: dibenzyl sulfoxide cocrystal

Study of supramolecular frameworks having aliphatic dicarboxylic acids, N,N′-bis(salicyl)ethylenediamine and N,N′-bis(salicyl)butylenediamine

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