Pharmaceutical salts and cocrystals involving amino acids: A brief structural overview of the state-of-art

Tilborg, Anaëlle; Norberg, Bernadette; Wouters, Johan

doi:10.1016/j.ejmech.2013.11.045

Cited by 104 publications

(77 citation statements)

References 122 publications

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“…Meanwhile, the endotherm profile of IBP-GLY shows the presence of two peaks which correspond to pure IBP and GLY components, and with no new peak detected, which could indicate that cocrystal formation did not take place. L-proline appears to be an excellent candidate as a CCF as it shares the zwitterionic α-ammoniumcarboxylate synthon, which is common to all other natural amino acids favouring the main chain atom interaction [7]. Different with other amino acids, Lproline is a constrained, rather rigid compound.…”

Section: Ionization Constant Rule For Co-crystals Formationsmentioning

confidence: 99%

“…Different with other amino acids, Lproline is a constrained, rather rigid compound. In terms of formation of co-crystals, this rigidity can certainly be viewed as an entropic advantage over other, more flexible, conformer (entropic contribution) [7]. Assessment of Lproline as a CCF was further investigated using different stoichiometric mol ratio, i.e.…”

Section: Ionization Constant Rule For Co-crystals Formationsmentioning

confidence: 99%

“…Ibuprofen was used as an API while amino acid as CCF is believed to improve the solubility of the API by cocrystallization process due to its zwitterionic state. However, it depends on the side chain of the amino acids which can be acidic or basic and strongly modifies the behaviour of the molecules [7].…”

Section: Introductionmentioning

confidence: 99%

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Ibuprofen-Amino Acids Co-Crystal Screening Via Co-Grinding Methods

et al. 2016

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Abstract. The importance of pharmaceutical co-crystals now has been recognized in order to improve the research and development in pharmaceutical industries. Low solubility of active pharmaceutical ingredient (API) has led to the growth of new pharmaceutical co-crystals formation as it enhances the physicochemical properties of the API. In this works, preparation of new co-crystal formation between ibuprofen (IBP) with selected amino acid compounds were performed by using dry grinding and liquid assisted grinding (LAG) techniques. Ibuprofen (IBP) was selected as the API meanwhile glycine (GLY), L-alanine (ALA) and L-proline (PRO) were selected as co-crystal former (CCF) agents. The products of IBP-co-former from grinding experiments for the formation of co-crystals were characterized and verified using X-Ray Powder Diffraction (XRPD), Differential Scanning Calorimetry (DSC) and Fourier Transform Infra-Red Spectroscopy (FTIR). The finding reveals that the IBP-PRO co-crystals have successfully formed. For IBP-PRO system, new crystalline peaks from XRPD were recorded at 2θ values of 4.374°, 5.436° and 10.944° from dry grinding technique and 4.41°, 5.436° and 10.962° for liquid assisted grinding (LAG) technique. A new melting point of 257.49 °C was discovered for IBP-ALA indicates the possibility of co-crystals formation. On the other hand, the analysis for IBP-GLY shows that no co-crystals formed in the system.

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Section: Ionization Constant Rule For Co-crystals Formationsmentioning

confidence: 99%

Section: Ionization Constant Rule For Co-crystals Formationsmentioning

confidence: 99%

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Ibuprofen-Amino Acids Co-Crystal Screening Via Co-Grinding Methods

et al. 2016

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“…To the best of our knowledge, the Arb zwitterion has not been previously seen in any of the drug crystal forms, and the [Arb + Suc] cocrystal seems to be the first found instance. Cocrystals with zwitterionic co-formers have been reported in the literature, and the most numerous examples can be found among amino acids [33]. Multicomponent crystals containing zwitterionic API molecule and neutral co-former are less frequent, but also known and described [34][35][36][37].…”

Section: Crystal Structuresmentioning

confidence: 99%

Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids

et al. 2015

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Salts of the antiviral drug arbidol (umifenovir) (Arb) with maleate (Mlc) and fumarate (Fum) anions have been obtained, and their crystal structures have been described. The crystal structure of arbidol maleate has been redetermined by single crystal X-ray diffraction at 180K. A new arbidol cocrystal in zwitterion form with succinic acid (Suc) has also been found and characterized. The arbidol zwitterion was not previously seen in any of the drug crystal forms, and the [Arb + Suc] cocrystal seems to be the first found instance. Analysis of the conformational preferences of the arbidol molecule in the crystal structures has shown that it adopts two types of conformations, namely "open" and "closed" ones. Thermal stability of the arbidol salts and cocrystal have been analyzed by means of differential scanning calorimetry, thermogravimetric, and mass-spectrometry analysis. The dissolution study of the arbidol salts and cocrystal performed in aqueous buffer solutions with pH 1.2 and 6.8 has shown that both the salts and the cocrystal dissolve incongruently to form an arbidol hydrochloride monohydrate at pH 1.2 and an OPEN ACCESSCrystals 2015, 5 651 arbidol base at pH 6.8, respectively. The cocrystal reaches the highest solubility level in both pH 1.2 and pH 6.8 solutions.

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“…R-mandelic acid has been used as the resolving agent whereby, a 1:2 molar ratio of R-mandelic acid and DL-tryptophan in aqueous ethanol gave L-tryptophane R-mandelate 1.5 H 2 O [13]. Recent reviews have also summarised the structures involving amino acids [14][15][16]. A search of the Cambridge Structural Database [17] gave twelve results when the zwitterionic form of tryptophan was entered as the search query; nine of the structures involve L-tryptophan [13,[18][19][20][21][22][23][24] one structure comprised of D-tryptophan with naproxen [25] and the remaining two structures are pure DL-tryptophan [26,27].…”

Section: Introductionmentioning

confidence: 99%

Salts of Tryptophan with p-Toluenesulphonic Acid and Camphorsulphonic Acids

Sayed

Jacobs

2015

J Chem Crystallogr

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Co-crystallisation of DL-tryptophan with p-toluenesulphonic acid, R-camphor-10-sulphonic acid and S-camphor-10-sulphonic acid resulted in salts. For all the structures, the amino acid is in the cationic form with the proton transferred from the acidic co-former to the amino acid. R-camphor-10-sulphonic acid and S-camphor-10-sulphonic acid were unsuccessful at resolving DL-tryptophan. Dissolution of the respective camphorsulphonic acid and DL-tryptophan in methanol/water gave crystals which contained equimolar amounts of the D-and the L-tryptophan. The following salts were also obtained in aqueous acetonitrile; (2L-TRP ? )(2S-CSA -)Á(H 2 O) from a mixture of L-TRP/S-CSA and (D-TRP ? )(S-CSA -) from a mixture of D-TRP/S-CSA. The crystal structures and the thermal stability of the salts have been determined. (DL-TRP ? )(p-TSA -) solved in P2 1 /c with a = 19.422(2) Å , b = 5.5456(7) Å , c = 16.488(2) Å and b = 102.357(2)°. (D-TRP ? )(L-TRP ? )(2R-CSA -) solved in P2 1 with a = 12.780(3) Å , b = 10.411(2) Å , c = 32.574(7) Å and b = 97.60(3)°. (D-TRP ? )(L-TRP ? )(2S-CSA -) solved in P2 1 with a = 12.783(3) Å , b = 10.410(2) Å , c = 32.564(7) Å and b = 97.44(3)°. (2L-TRP ? )(2S-CSA -)-(H 2 O) solved in P2 1 with a = 13.1761(12) Å , b = 10.3092(10) Å , c = 16.6268(16) Å and b = 104.435(2)°. (D-TRP ? )(S-CSA -) solved in P2 1 2 1 2 1 with a = 6.4185(13) Å , b = 12.700(3) Å , c = 25.173(5) Å and a = b = c = 90°.Graphical Abstract DL-tryptophan forms salts with ptoluenesulphonic acid, R-camphor-10-sulphonic acid and S-camphor-10-sulphonic acid. L-tryptophan forms a salt hydrate with S-camphor-10-sulphonic acid and D-tryptophan forms a salt with S-camphor-10-sulphonic acid. The crystal structures and the thermal stability of the salts are reported.Electronic supplementary material The online version of this article (

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Pharmaceutical salts and cocrystals involving amino acids: A brief structural overview of the state-of-art

Cited by 104 publications

References 122 publications

Ibuprofen-Amino Acids Co-Crystal Screening Via Co-Grinding Methods

Ibuprofen-Amino Acids Co-Crystal Screening Via Co-Grinding Methods

Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids

Salts of Tryptophan with p-Toluenesulphonic Acid and Camphorsulphonic Acids

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