Cocrystallization via planetary milling: Enhancing throughput of solid-state screening methods

Bysouth, Stephen R.; Bis, Joanna A.; Igo, David H.

doi:10.1016/j.ijpharm.2011.03.037

Cited by 49 publications

(37 citation statements)

References 16 publications

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“…The influence of the relative humidity was evaluated by acquiring the X-ray diffraction data at 60, 70 and 80 % RH and 40 °C for samples that were pre-milled for 5 minutes at 20 and 25 Hz. The influence of the pre-milling frequency was considered by performing the milling for 5 minutes with a frequency of 20,25,30 Hz and recording the kinetic data of cocrystallisation at 60% RH and 40 °C.…”

Section: Methodsmentioning

confidence: 99%

“…Cocrystals can form spontaneously in physical mixtures of their compounds, [5][6][7][8] but purposefully they are prepared by crystallisation from solvent, [9][10][11][12][13][14][15] from melt, 16,17 by spray drying 18,19 or by mechanical treatment. [20][21][22] The latter method has gained recognition in scientific laboratories and is employed extensively to synthesize new polymorphs, cocrystals and salts. It is fast, easy to perform, requires minimal or no use of solvent 23 and offers a pure product with a controlled polymorphic yield.…”

Section: Introductionmentioning

confidence: 99%

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Mechanistic and Kinetic Insight into Spontaneous Cocrystallization of Isoniazid and Benzoic Acid

et al. 2015

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Solid-state cocrystallization is of contemporary interest because it offers an easy and efficient way to produce cocrystals, which are recognized as prospective pharmaceutical materials. Research explaining solid-state cocrystallization mechanisms is important but still too scarce to give a broad understanding of factors governing and limiting these reactions. Here we report an investigation of the mechanism and kinetics of isoniazid cocrystallization with benzoic acid. This reaction is spontaneous; however, its rate is greatly influenced by environmental conditions (humidity and temperature) and pretreatment (milling) of the sample. The acceleration of cocrystallization in the presence of moisture is demonstrated by kinetic studies at elevated humidity. The rate dependence on humidity stems from moisture facilitated rearrangements on the surface of isoniazid crystallites, which lead to cocrystallization in the presence of benzoic acid vapor. Furthermore, premilling the mixture of the cocrystal ingredients eliminated the induction time of the reaction and considerably increased its rate.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mechanistic and Kinetic Insight into Spontaneous Cocrystallization of Isoniazid and Benzoic Acid

et al. 2015

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“…High throughput screening (HTS) technologies have been employed for CCF screening. [10][11][12][13][14][15] However, CCF selection by HTS remains a time-and resource-consuming task. Therefore, an effective pre-screening method for CCF selection would be valuable for drug discovery and development.…”

mentioning

confidence: 99%

Stability Order of Caffeine Co-crystals Determined by Co-crystal Former Exchange Reaction and Its Application for the Validation of in Silico Models

2015

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The purpose of the present study was to determine the thermodynamic stability orders of co-crystals by co-crystal former (CCF) exchange reactions. Caffeine (CA) was employed as a model drug. The CCF exchange reaction was performed by liquid-assisted grinding using ethanol. When oxalic acid (OX) was added to CA-citric acid co-crystal (CA-CI), CA-CI converted to CA-OX, suggesting that CA-OX is more stable than CA-CI. The stability orders of other co-crystals were determined in the same manner. The stability order of CA co-crystals was determined as CA-OX≈CA-p-hydroxybenzoic acid (HY)>CA-CI>CA-malonic acid>CA-maleic acid. The stability order correlated with the difference in hydrogen bond energy estimated in silico, except for CA-HY. The π-π stacking in CA-HY was suggested as a reason for this discrepancy. The CCF exchange reaction was demonstrated as a useful method to determine the stability order of co-crystals, which can be used for the validation of in silico parameters to predict co-crystal formation.Key words co-crystal; co-crystal former; exchange reaction; caffeine; hydrogen bond energy Co-crystals have recently received much attention as a means of improving physicochemical properties of active pharmaceutical ingredients.1-10) The number of potential co-crystal formers (CCFs) can reach up to several hundred; therefore, an efficient strategy for CCF screening in drug discovery and development is required. High throughput screening (HTS) technologies have been employed for CCF screening.10-15) However, CCF selection by HTS remains a time-and resource-consuming task. Therefore, an effective pre-screening method for CCF selection would be valuable for drug discovery and development. In the case of salt selection, the difference in pK a values between a drug and a counterion (ΔpK a ) has been used as a criterion for the selection of potential counter-ion candidates.16) Similarly, some in silico physicochemical parameters for CCF selection were proposed by several research groups. [17][18][19][20] For example, the difference in hydrogen bond energy between a co-crystal and each of the sole components (ΔE) was proposed by Musumeci et al., based on the hypothesis that the formation of a co-crystal becomes more probable as ΔE becomes larger.21-23) However, ΔE has not been rigorously validated due to the lack of information about the stability order of co-crystals. The stability order of co-crystals can be determined by CCF exchange reactions. In the literature, there were a few studies on the CCF exchange reactions (a sulfonamide derivative 24) and carbamazepine 25) ). However, in these studies, only a few CCFs were employed so that the data is insufficient for validating in silico models.The purpose of the present study was to determine the stability orders of co-crystals by CCF exchange reaction. Caffeine (CA) was employed as a model drug. The stability order of five CA co-crystals was determined using the CCF exchange reaction. The stability order was then compared with the ΔE estimated in silico.

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“…Grinding techniques are of two types: neat or dry grinding and wet grinding. In dry grinding, drug and coformer are mixed together in a stoichiometric ratio and ground them by using either mortar and pestle or ball mill [102] . Wet Grinding was performed in a similar manner that of neat grinding by addition of some drops of solvent in the mixture [103,104] .…”

Section: Grinding Methodmentioning

confidence: 99%

Pharmaceutical Cocrystals: An Overview

Kumar¹,

Nanda²

2017

pharmaceutical-sciences

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Cocrystallization via planetary milling: Enhancing throughput of solid-state screening methods

Cited by 49 publications

References 16 publications

Mechanistic and Kinetic Insight into Spontaneous Cocrystallization of Isoniazid and Benzoic Acid

Mechanistic and Kinetic Insight into Spontaneous Cocrystallization of Isoniazid and Benzoic Acid

Stability Order of Caffeine Co-crystals Determined by Co-crystal Former Exchange Reaction and Its Application for the Validation of in Silico Models

Pharmaceutical Cocrystals: An Overview

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