Sixth polymorph of aripiprazole - an antipsychotic drug

Nanubolu, Jagadeesh Babu; Sridhar, Balasubramanian; Babu, Vaddela Sudheer; Jagadeesh, B.; Ravikumar, K.

doi:10.1039/c2ce25306b

Cited by 39 publications

(44 citation statements)

References 51 publications

(4 reference statements)

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“…Very recently, a low-temperature phase with an eighth polymorphic form has been reported (Delaney et al, 2014). The existence of eight polymorphic forms of aripiprazole can be attributed to a very high degree of conformational freedom, significant differences in the hydrogen bonding and the influence of crystal-packing effects (Nanubolu et al, 2012). Centrosymmetric forms have the amide dimer (Fig.…”

Section: Resultsmentioning

confidence: 99%

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The first polymorph in the family of nucleobases: a second form of cytosine

2015

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A new polymorph of cytosine, C4H5N3O, is reported half a century after the report of its first known crystal structure [Barker & Marsh (1964). Acta Cryst. 17, 1581-1587]. Cytosine thus provides the first polymorphic example in the category of parent nucleobases. The new form, denoted (Ib), was observed unexpectedly during an attempt to cocrystallize cytosine with catechol. Form (Ib) crystallizes in the orthorhombic centrosymmetric space group Pccn with two molecules in the asymmetric unit. The previously known form, denoted (Ia), crystallizes in the orthorhombic noncentrosymmetric space group P212121. The cytosine molecule is planar in both forms. Hydrogen-bonding interactions are also similar for both forms. Infinite one-dimensional ribbons composed of cytosine base-pair dimers in R2(2)(8) arrangements are observed in both (Ia) and (Ib). However, the way that the ribbons are packed differs in (Ia) and (Ib). This appears to guide the centrosymmetric versus noncentrosymmetric space-group selection through the formation of an inversion-related motif in polymorph (Ib) and a helical propagation in polymorph (Ia). A few selected polymorphic systems have been gathered from the Cambridge Structural Database to understand possible structural features responsible for achiral molecules adopting centro- and noncentrosymmetric space groups.

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Section: Resultsmentioning

confidence: 99%

“…The antipsychotic drug aripiprazole (MELFIT; Braun et al, 2009;Nanubolu et al, 2012) is the most structurally characterized, with seven polymorphs reported in the CSD in this category. Very recently, a low-temperature phase with an eighth polymorphic form has been reported (Delaney et al, 2014).…”

Section: Resultsmentioning

confidence: 99%

The first polymorph in the family of nucleobases: a second form of cytosine

2015

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“…9,10 In addition, CCDC 904819 provides the structural information on aripiprazole HCl salt form with the associated publications by Nanubolu et al,. 11 We provide the summary of relevant CCDC information in SI Table 1. These literature data on calculated and experimental PXRD data are compared with our experimental PXRD data (SI Fig.…”

Section: Pxrd Analysismentioning

confidence: 99%

Solution-Mediated Phase Transformation of Aripiprazole: Negating the Effect of Crystalline Forms on Dissolution and Oral Pharmacokinetics

Chung¹,

Kim²,

Ban

et al. 2020

Journal of Pharmaceutical Sciences

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We aimed to evaluate the effect of crystalline forms of aripiprazole, an antipsychotic drug for schizophrenia, on the dissolution rates and oral pharmacokinetics. Solubility, intrinsic dissolution rates, and tablet dissolution rates of the monohydrate (MA) and the anhydrous form (AA) were measured in various aqueous media while monitoring the phase transformation by ATR-FTIR. And their oral pharmacokinetics in dogs were compared. The intrinsic dissolution rate of MA was lower compared to AA, confirming its thermodynamic stability relative to AA in water. Phase transformations during the solubility measurement were media-dependent: In simulated gastric fluid, both AA and MA changed to HCl salt form, whereas AA and HCl salt form transformed to MA in simulated intestinal fluid. In vitro dissolution rates and dog oral pharmacokinetics of AA and MA tablets were similar. The results suggest that the solutionmediated transformation to HCl salt or MA negates the effect of different crystalline forms on dissolution rates in vivo and, consequently, on oral pharmacokinetics. We emphasize the importance of the dissolution tests employing various bio-relevant media for better prediction of in vivo performance and the selection of a solid form for development.

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“…Although polymorphism is common, there is only a limited number of compounds with over four characterised forms. 18 Compounds with more than eight known polymorphs include ROY, [19][20][21][22] aripiprazole, [23][24][25][26] flufenamic acid 18 and galunisertib. 27 Matzger et al proposed the concept of "polymorphophore" 28 which is a chemical substructure likely to induce rich polymorphic behaviour in a compound.…”

Section: Introductionmentioning

confidence: 99%