Salts, solvates and hydrates of the multi-kinase inhibitor drug pazopanib with hydroxybenzoic acids

Sunil, K.; Baidya, Debjani; Nangia, Ashwini

doi:10.1039/d1ce00785h

Cited by 18 publications

(15 citation statements)

References 63 publications

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“…(4) The least-soluble crystals which precipitate from solution could well be a metastable form energetically based on calculations in the gas phase. ( 5) Hydrogen bond strength is directed not only by the acid−base pK a difference but also by the electrostatic potential map 86 at the N acceptor, ancillary hydrogen bonding groups, 87 and proton affinity and pK a equalization. 88 2.3.3.…”

Section: Cocrystal Design Approachesmentioning

confidence: 99%

Crystal Engineering of Pharmaceutical Cocrystals in the Discovery and Development of Improved Drugs

2022

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The subject of crystal engineering started in the 1970s with the study of topochemical reactions in the solid state. A broad chemical definition of crystal engineering was published in 1989, and the supramolecular synthon concept was proposed in 1995 followed by heterosynthons and their potential applications for the design of pharmaceutical cocrystals in 2004. This review traces the development of supramolecular synthons as robust and recurring hydrogen bond patterns for the design and construction of supramolecular architectures, notably, pharmaceutical cocrystals beginning in the early 2000s to the present time. The ability of a cocrystal between an active pharmaceutical ingredient (API) and a pharmaceutically acceptable coformer to systematically tune the physicochemical properties of a drug (i.e., solubility, permeability, hydration, color, compaction, tableting, bioavailability) without changing its molecular structure is the hallmark of the pharmaceutical cocrystals platform, as a bridge between drug discovery and pharmaceutical development. With the design of cocrystals via heterosynthons and prototype case studies to improve drug solubility in place (2000–2015), the period between 2015 to the present time has witnessed the launch of several salt–cocrystal drugs with improved efficacy and high bioavailability. This review on the design, synthesis, and applications of pharmaceutical cocrystals to afford improved drug products and drug substances will interest researchers in crystal engineering, supramolecular chemistry, medicinal chemistry, process development, and pharmaceutical and materials sciences. The scale-up of drug cocrystals and salts using continuous manufacturing technologies provides high-value pharmaceuticals with economic and environmental benefits.

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Section: Cocrystal Design Approachesmentioning

confidence: 99%

Crystal Engineering of Pharmaceutical Cocrystals in the Discovery and Development of Improved Drugs

2022

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“…From TG and DSC thermograms, it can be found that S3 , S4 , and S5 are free of solvent/water, while S1 shows an endothermic peak of desolvation at 117 °C, accompanied by weight loss in the range of ∼74–124 °C in the TG curve, and S2 shows a dehydration temperature peak at 137 °C, supported by the mass loss in ∼75–152 °C temperature range in the TG curve. Water and methanol molecules are coming out of crystal lattices at high temperatures above their respective boiling point (78 °C for methanol and 100 °C for water), and this phenomenon can be attributed to strong hydrogen bonds associated with crystalline methanol and water molecules. , S1 , S2 , S4 , and S5 show a similar endothermic peak at ∼178 °C, which might be ascribed to a phase transition. However, it is difficult to estimate the thermodynamic stability relationship of these five forms based on melting points (as an indicator of solid-form stability), according to Burger and Ramberge’s heat of fusion rule, because TMZ–PHBA cocrystals and TMZ pure drugs decompose upon heating.…”

Section: Resultsmentioning

confidence: 99%

“…Water and methanol molecules are coming out of crystal lattices at high temperatures above their respective boiling point (78 °C for methanol and 100 °C for water), and this phenomenon can be attributed to strong hydrogen bonds associated with crystalline methanol and water molecules. 53,54 S1, S2, S4, and S5 show a similar endothermic peak at ∼178 °C, which might be ascribed to a phase transition. However, it is difficult to estimate the thermodynamic stability relationship of these five forms based on melting points (as an indicator of solid-form stability), according to Burger and Ramberge's heat of fusion rule, 55 because TMZ−PHBA cocrystals and TMZ pure drugs decompose upon heating.…”

Section: Mep Analysismentioning

confidence: 87%

Five Cocrystal Forms of Antitumor Drug Temozolomide with p-Hydroxybenzoic Acid: Structure, Computational Analysis, Characterizations, Stability, and Transformation

Zhang

Xing

et al. 2022

Crystal Growth & Design

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Temozolomide (TMZ) is a first-line antitumor drug but suffers from troubling stability issues related to degradation during storage and processing. In this paper, cocrystallization of TMZ with p-hydroxybenzoic acid (PHBA) produced five forms including one methanolate, one hydrate, two polymorphic forms in 2:1, and one solvent-free form in 1:1 ratio, designated as TMZ/ PHBA/MeOH (1:1:1, S1), TMZ/PHBA/H 2 O (1:1:1, S2), TMZ/PHBA (2:1-form I, S3; 2:1-form II, S4), and TMZ/PHBA (1:1, S5). Except for S5, the other four forms were characterized and evaluated in detail by single-crystal X-ray diffraction. Powder X-ray diffraction, Fourier transform infrared spectroscopy, thermal analysis, and stability test were conducted for all five forms. The crystal form differences are mainly ascribed to the incorporation of solvent/water molecules, supramolecular synthon distinctions, and conformation flexibility of TMZ. The feeding ratio of starting components and the solvent used in the experiments both play a decisive role in the resulting form.

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“…The CQO and C-O distances in the COO moiety of the COOH group are very close to each other (DD is small), indicative of a carboxylate COO À acceptor. 18 The red shift in the IR stretching frequency (COOH in the coformer to COO À in the binary product; Table S3, ESI †) and the ORTEP plots (Fig. S1, ESI †) confirm the NFPD-FBA adducts as salts.…”

mentioning

confidence: 79%

Fluorobenzoic acid coformers to improve the solubility and permeability of the BCS class IV drug naftopidil

et al. 2022

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Salts, solvates and hydrates of the multi-kinase inhibitor drug pazopanib with hydroxybenzoic acids

Abstract: The marketed formulation of Pazopanib (PAZ) suffers from low and variable bioavailability because of its poor dissolution rate and photostability issues. The drug falls under Biopharmaceutics Classification System (BCS) Class...

Cited by 18 publications

References 63 publications

Crystal Engineering of Pharmaceutical Cocrystals in the Discovery and Development of Improved Drugs

Crystal Engineering of Pharmaceutical Cocrystals in the Discovery and Development of Improved Drugs

Five Cocrystal Forms of Antitumor Drug Temozolomide with p-Hydroxybenzoic Acid: Structure, Computational Analysis, Characterizations, Stability, and Transformation

Fluorobenzoic acid coformers to improve the solubility and permeability of the BCS class IV drug naftopidil

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