A new cocrystal and salts of itraconazole: Comparison of solid-state properties, stability and dissolution behavior

Shevchenko, Anna; Bimbo, Luís M.; Miroshnyk, Inna; Haarala, Jorma; Jelínková, Kristýna; Syrjänen, Karí; Veen, Bert van; Kiesvaara, Juha; Santos, Hélder A.; Yliruusi, Jouko

doi:10.1016/j.ijpharm.2012.06.045

Cited by 84 publications

(55 citation statements)

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“…Among these, the traditional solution crystallization appears the industrially preferable method because the process is well established, easily scalable, and less prone to contamination [11,12]. However, there were cases where the solution method was not successful in yielding cocrystals, such as caffeine/glutaric acid, paracetamol/oxalic acid, and itraconazole/malonic acid, in their pure forms, which could be obtained through liquid-assisted grinding [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Liquid-Assisted Grinding to Prepare a Cocrystal of Adefovir Dipivoxil Thermodynamically Less Stable than Its Neat Phase

2015

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Liquid-assisted grinding was employed to generate a cocrystal of adefovir dipivoxil (AD) and glutaric acid (GLU), which had not been successfully obtained through solution crystallization. The cocrystal formation was confirmed with powder X-ray diffraction, and its thermal stability and release behavior were studied through differential scanning calorimetry and dissolution experiments, respectively. The AD/GLU cocrystal was less stable than neat AD phase and the previously reported AD cocrystals with other dicarboxylic acids, such as suberic acid and succinic acid. This suggests that the intermolecular interactions of the AD/GLU cocrystal are probably weaker than the other crystal phases. The release behavior of the AD/GLU was comparable with the cocrystal with suberic acid. The current study verifies the effectiveness of the liquid-assisted grinding for the preparation of the thermodynamically less stable cocrystal phase.

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Section: Introductionmentioning

confidence: 99%

Liquid-Assisted Grinding to Prepare a Cocrystal of Adefovir Dipivoxil Thermodynamically Less Stable than Its Neat Phase

2015

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“…The both drug molecule-counter molecule pairs can form the co-crystals with a molar ratio of ITZ : counter=2 : 1 that improve the solubility of drug in a previous study. 23,24) In this study, we discussed the synthon interactions in the co-amorphouses and the characteristic properties depending on the difference of counter molecule, especially their stability, and evaluated their relevancy on drug development in comparison with the properties of the co-crystals that are composed of the same drug-counter molecule pairs.…”

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confidence: 99%

Physicochemical Evaluation and Developability Assessment of Co-amorphouses of Low Soluble Drugs and Comparison to the Co-crystals

Yamamoto

Kojima

Karashima

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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To judge the developability and analyze functional mechanism of co-amorphouses, we investigated the physicochemical properties of co-amorphouses and compare the properties with the co-crystals having the same drug and counters. Co-amorphous compounds are a novel approach to improve the physicochemical properties of drugs. A co-amorphous is in an amorphous solid state allowing non-ionic interactions between drug molecules and counter molecules. The co-amorphous compounds composed of itraconazole (ITZ) with the organic carboxyl acid, fumaric acid (FA) or L-tartaric acid (TA), were prepared by mechanical grinding. Potential interactions within ITZ-FA co-amorphous were assessed by Raman spectroscopy. ITZ-FA coamorphous was not crystallized as the co-crystal or as a single ITZ crystal, suggesting that the amorphous state, like the amorphous solid dispersion, was physically stable and that ITZ-FA co-amorphous was also chemically stable. In contrast, no clear interactions were observed within ITZ-TA co-amorphous, and the coamorphous was physically stable but chemically unstable. The solubility of the co-amorphous state was much higher than those of ITZ crystal and the co-crystals and was almost identical to that of amorphous ITZ. A co-amorphous compound like ITZ-FA co-amorphous might be feasible to implement in the development of solid drug products and bring some merits compared to the co-crystals, and the function is governed by the interaction between a drug and a counter. The co-amorphous approach may be an effective strategy for drug development and can contribute to the production of novel drugs with improved functions.Key words co-amorphous; co-crystal; stability; solubilization; interaction; itraconazole Solubility improvement is one of the most important challenges for drug development of poorly soluble drugs. Amorphization of drugs is a major effective strategy to prepare solubilized formulations, because the crystal packing effect on a drug substance significantly decreases its solubility. 1-3)An amorphous compound is in a higher energy state and has a higher mobility than a crystalline compound, improving its solubility and dissolution properties. However, due to the higher energy state, the physical and chemical stability of amorphous compounds are relatively lower than those of a crystal. 4,5) In many cases, an amorphous drug is formulated by solid dispersion with hydrophilic polymers to improve the amorphous drug stability. [6][7][8] The complex formed with polymers can prevent the drug's crystallization and maintain the physical stability of the amorphous state. Generally, weak interactions cannot sufficiently stabilize amorphous drugs. 9)The prediction and design leading to the interactions between the drug and the polymer are still difficult to accomplish. Therefore, solid dispersions combined with several kinds and amounts of polymers need to be tested.As another approach to enhance a drug's solubility, pharmaceutical co-crystals have been investigated and adapted to the drug development processes in...

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“…Samples were filtered through whatman filter paper, diluted and analyzed at 290 nm using Shimadzu UV-1800 Japan Spec, spectrophotometer. [29,30] Analysis of molecular complexation by solubility…”

Section: Drug Contentmentioning

confidence: 99%

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Payghan¹

2017

AJP

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Aim: The objective of this study was to investigate whether the miscibility of a drug and coformer, as predicted by Hansen solubility parameter (HSP), can indicate cocrystal formulation. It was also our aim to evaluate various HSP-based approaches in miscibility predication. HSP for fenofibrate drug over 20 coformers was calculated according to the group contribution method. Materials and Methods: The selection of coformer was based on hydrogen bond present in structure which clearly shows the importance of hydrogen bonding in forming cocrystals. Solubility parameters for solutes are obtained by group contribution method. Result and Discussion: In the present investigation, these methods were employed to arrive at the solubility parameter values. The basic steps in Fedor's method are to open the rings and treat the resultant structure as an open-chain compound. These were sum-up, and the solubility parameter was calculated as square root of the sum of energy of mixing substituent constants divided by the sum of molar volume substituent constants. Hoy's procedure expressed in the ratio of molar attraction constant to molar volume. The resultant δ values of drug and coformers are compared, and their solid state miscibility is expressed. Possibility of cocrystal formulation by Krevelen's is Δδ < 5 MP and Greenhalgh Δδ < 7 MP. The present investigation deals with the formulation of coformer (saccharin, succinic acid, and sucrose) based on cocrystals fenofibrate by different methods and solid-state characterization of prepared cocrystals. Fenofibrate and coformers in molar ratio were used to formulate molecular complexes by solution evaporation, slow evaporation, antisolvent addition, net grinding method, and solvent-drop grinding methods. The prepared molecular complexes were characterized by powder X-ray diffraction, differential scanning calorimetry, Fourier-transform infrared spectroscopy, and in vitro dissolution study. Conclusion: Considerable improvement in the dissolution rate of fenofibrate from optimized cocrystal formulation was due to an increased solubility that is attributed to the supersaturation from the fine cocrystals which is faster due to large specific surface area of small particles and prevention of phase transformation to pure fenofibrate.

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A new cocrystal and salts of itraconazole: Comparison of solid-state properties, stability and dissolution behavior

Cited by 84 publications

References 31 publications

Liquid-Assisted Grinding to Prepare a Cocrystal of Adefovir Dipivoxil Thermodynamically Less Stable than Its Neat Phase

Liquid-Assisted Grinding to Prepare a Cocrystal of Adefovir Dipivoxil Thermodynamically Less Stable than Its Neat Phase

Physicochemical Evaluation and Developability Assessment of Co-amorphouses of Low Soluble Drugs and Comparison to the Co-crystals

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