A carbamazepine-indomethacin (1 : 1) cocrystal produced by milling

Majumder, Mridul; Buckton, Graham; Rawlinson-Malone, Clare Frances; Williams, Adrian C.; Spillman, Mark J.; Shankland, Norman; Shankland, Kenneth

doi:10.1039/c1ce05650f

Cited by 33 publications

(24 citation statements)

References 17 publications

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“…The core hydrogen bonding motifs are essentially the same in both the previously reported CBZ:IND form I [24] and CBZ:IND form II, taking the general form illustrated in Figure 3b, i.e., a central R 2 2 (8) synthon and an N-H•••O hydrogen bond between the amide of the CBZ and the oxygen of the 4-chlorobenzoyl group of the IND. The density of form II (1.398 g cm −3 ) is higher than that of form I (1.351 g cm −3 ), which is indicative of more efficient packing in form II.…”

Section: Atom Cbz:ind Form II Indmet03supporting

confidence: 72%

“…Cl 1 0.118 Å 0.058 Å C 9 0.234 Å 0.119 Å Taken together, these geometry changes affect the location of a significant amount of X-ray scattering power, explaining why the initial rigid-body Rietveld refinement based on the starting INDMET03 geometry was unsuccessful. The core hydrogen bonding motifs are essentially the same in both the previously reported CBZ:IND form I [24] and CBZ:IND form II, taking the general form illustrated in Figure 3b, i.e., a central (8) synthon and an N-H⋅⋅⋅O hydrogen bond between the amide of the CBZ and the oxygen of the 4-chlorobenzoyl group of the IND. The density of form II (1.398 g cm −3 ) is higher than that of form I (1.351 g cm −3 ), which is indicative of more efficient packing in form II.…”

Section: Atom Cbz:ind Form II Indmet03supporting

confidence: 71%

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Co-Crystal Structures of Furosemide:Urea and Carbamazepine:Indomethacin Determined from Powder X-Ray Diffraction Data

Rahal

Majumder²,

Spillman

et al. 2020

Crystals

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Co-crystallization is a promising approach to improving both the solubility and the dissolution rate of active pharmaceutical ingredients. Crystal structure determination from powder diffraction data plays an important role in determining co-crystal structures, especially those generated by mechanochemical means. Here, two new structures of pharmaceutical interest are reported: a 1:1 co‑crystal of furosemide with urea formed by liquid-assisted grinding and a second polymorphic form of a 1:1 co‑crystal of carbamazepine with indomethacin, formed by solvent evaporation. Energy minimization using dispersion-corrected density functional theory was used in finalizing both structures. In the case of carbamazepine:indomethacin, this energy minimization step was essential in obtaining a satisfactory final Rietveld refinement.

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Section: Atom Cbz:ind Form II Indmet03supporting

confidence: 72%

Section: Atom Cbz:ind Form II Indmet03supporting

confidence: 71%

Co-Crystal Structures of Furosemide:Urea and Carbamazepine:Indomethacin Determined from Powder X-Ray Diffraction Data

Rahal

Majumder²,

Spillman

et al. 2020

Crystals

Self Cite

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“…Majumder et al reported [83] a carbamazepine-indomethacin cocrystal using the powder X-ray diffraction (PXRD) structure solution. PXRD data shows a clear formation of cocrystal during ball mill grinding.…”

Section: Carbamazepine Cocrystal Systemmentioning

confidence: 99%

Drug‑Drug and Drug‑Nutraceutical Cocrystal/Salt as Alternative Medicine for Combination Therapy: A Crystal Engineering Approach

2018

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The pre-formulation of pharmaceutical cocrystals and salts is a concept of crystal engineering that has emerged as a promising technique for drug development in pharmaceutical industry. Recent introduction of pharmaceutical cocrystals in regulatory guidelines of US Food and Drug Administration (FDA) made them one of the potential alternatives when salt preparation is not feasible. Apart from generally regarded as safe (GRAS) coformers, drug-drug and drug-nutraceutical cocrystals are recent additions to pharmaceutical cocrystal family that have additional health benefits. Indeed, preparation of salt forms is a routine practice to deal with inadequacies associated with the active pharmaceutical ingredient (API) and happens to be a potentially reliable method. Amongst them, drug-drug and drug-nutraceutical cocrystals have drawn significant importance in the recent past as they reduce drug load and cost effects during multiple disease diagnosis. However, one has to be prudent in the selection of drug molecules, the presence of complementary hydrogen bond synthon, disease management during multiple disease therapy, etc. that play important roles in their preparation. That is the reason why drug-drug cocrystals are scarce in the literature compared to pharmaceutical cocrystals containing GRAS coformers and salt forms. Herein, we discuss case studies preferably the reported drug-drug, drug-nutraceutical cocrystals, and a few salts with an emphasis on their role in physicochemical property modulation.

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“…These results, where reduced supersaturation is observed, are in contradiction with the current paradigm of formulating drugs together as an amorphous mixture or producing them as cocrystals for the purpose of improved dissolution and increased supersaturation. [7,[13][14][15]34] Therefore, the maximum achievable supersaturation for various ATV:RTV molar ratios was investigated in order to better understand this phenomenon.…”

Section: Atv and Rtv Miscibilitymentioning

confidence: 99%

Compromised in vitro dissolution and membrane transport of multidrug amorphous formulations

Alhalaweh

Bergström

Taylor

2016

Journal of Controlled Release

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Herein, the thermodynamic properties of solutions evolving from the non-sink dissolution of amorphous solid dispersions (ASDs) containing two or more drugs have been evaluated, focusing on the maximum achievable supersaturation and tendency of the system to undergo liquid-liquid phase separation (LLPS). Ritonavir (RTV) and atazanavir (ATV) were co-formulated with polyvinylpyrrolidone to produce ASDs with different molar ratios of each drug, and the dissolution profile of each drug was studied under non-sink conditions. The phase behavior of the supersaturated solutions generated by ASD dissolution was compared to that of supersaturated solutions generated by antisolvent addition. Dissolution of an ASD containing RTV, ATV and lopinavir (LPV) was also investigated. A thermodynamic model was used to predict the maximum achievable supersaturation for ASDs containing two and three drugs. In addition, a transport study with Caco-2 cells was conducted to evaluate the impact of co-addition of drugs on membrane transport. It was found that the formulation containing a 1:1 molar ratio of RTV and ATV achieved only 50% of the supersaturation attained by dissolution of the single drug systems. The maximum achievable concentration of ATV decreased linearly as the mole fraction of ATV in the formulation decreased and a similar trend was observed for RTV. For the dispersion containing a 1:1:1 molar ratio of RTV, ATV and LPV, the maximum concentration of each drug was only one third of that achieved for the single drug formulations. The decrease in the achievable supersaturation was well-predicted by the thermodynamic model for both the binary and ternary drug combinations. These observations can be explained by a decrease in the concentration at which the drugs undergo LLPS in the presence of other miscible drugs, thereby reducing the maximum achievable supersaturation of each drug. The reduced free drug concentration was reflected by a decreased flux across Caco-2 cells for the drug combinations compared to drug alone. This study sheds light on the complex dissolution and solution phase behavior of multicomponent amorphous dosage forms, in particular those containing poorly water soluble drugs, which may undergo supersaturation in vivo.

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A carbamazepine-indomethacin (1 : 1) cocrystal produced by milling

Cited by 33 publications

References 17 publications

Co-Crystal Structures of Furosemide:Urea and Carbamazepine:Indomethacin Determined from Powder X-Ray Diffraction Data

Co-Crystal Structures of Furosemide:Urea and Carbamazepine:Indomethacin Determined from Powder X-Ray Diffraction Data

Drug‑Drug and Drug‑Nutraceutical Cocrystal/Salt as Alternative Medicine for Combination Therapy: A Crystal Engineering Approach

Compromised in vitro dissolution and membrane transport of multidrug amorphous formulations

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