Solid-state compatibility studies of Ketoconazole-Fumaric acid co-crystal with tablet excipients

Kacsó, Irina; Rus, Lucia; Martin, Flavia; Miclăuş, Maria; Filip, Xenia; Dan, Monica

doi:10.1007/s10973-020-09340-4

Cited by 13 publications

(13 citation statements)

References 31 publications

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“…31 Hz, 2H). 13 Synthesis of N-(5-Bromopyridin-2-yl)benzamide. 2-Amino-5bromopyridine (1.90 g, 11.0 mmol) was dissolved in 50 mL of pyridine and cooled in an ice bath.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…1 H NMR (400 MHz, DMSO-d 6 ): δ 10.53 (s, 1H), 8.76 (ddd, J = 4.8, 1.7, 0.9 Hz, 1H), 8.46 (dd, J = 2.6, 0.7 Hz, 1H), 8.31 (dd, J = 8.9, 0.7 Hz, 1H), 8.22 (dt, J = 7.8, 1.1 Hz, 1H), 8.12 (td, J = 7.7, 1.7 Hz, 1H), 8.04 (dd, J = 8.9, 2.6 Hz, 1H), 7.74 (ddd, J = 7.6, 4.8, 1.3 Hz, 1H). 13 Synthesis of N-(5-Bromopyridin-2-yl)picolinamide. Picolinic acid (1.00 g, 8.13 mmol), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (4.00 g, 10.5 mmol), triethylamine (3.40 mL, 24.4 mmol), and 2-amino-5-bromopyridine (1.54 g, 8.90 mmol) were dissolved in 60 mL of DMF.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

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Mapping out the Relative Influence of Hydrogen and Halogen Bonds in Crystal Structures of a Family of Amide-Substituted Pyridines

Abeysekera

Day

Sinha

et al. 2020

Crystal Growth & Design

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The simultaneous use of hydrogen bonds and halogen bonds in crystal engineering strategies has previously been employed in order to generate new solid forms with applications in e.g. pharmaceutical and agrochemical industries. Unfortunately, it is not easy to predict how these will coexist or compete in systems where multiple structural outcomes are possible. To address this challenge, we have investigated the solid-state landscape of a family of amide-substituted pyridines, belonging to four series, N-(pyridin-2-yl)benzamides (Bz), N-(pyridin-2-yl)picolinamides (2Pyr), N-(pyridin-2-yl)nicotinamides (3Pyr) and N-(pyridin-2-yl)isonicotinamides (4Pyr), functionalized with three different halogen atoms (chlorine, bromine, and iodine). We analyzed crystal structures of 16 compounds and identified their primary intermolecular interactions. Within each series, the chlorinated and brominated compounds present the same primary hydrogen-bond interactions as shown by the nonhalogenated parent. The N-(pyridin-2-yl)benzamides assembled via NH···N(Py) synthons to form dimers, N-(pyridin-2-yl)picolinamides showed intramolecular N–H···N(Py) hydrogen bonding, and both N-(pyridin-2-yl)nicotinamides (3Pyr) and N-(pyridin-2-yl) isonicotinamides (4Pyr) assembled via NH···N(Py) synthons leading to the formation of chains or four-membered rings. In three out of the four series (Bz, 2Pyr, and 4Pyr) the chloro and bromo compounds were isostructural. Three out of the four iodinated compounds exhibited halogen bonds to a neighboring molecule. In two of these compounds, Bz-I and 2Pyr-I, the primary hydrogen bonding resembled that of the other members of the family, indicating that the interactions mediated via the iodine atom were complementary to rather than competitive with the hydrogen bonds. Two polymorphs of 4Pyr-I were found, and in both forms, a halogen bond was formed with the N(py) acceptor which was engaged in N–H···N hydrogen bonds in the other members of this family. Since iodine acted as a halogen-bond donor in four-fifths of the crystal structures of iodinated compounds, these results show that the solid-state assembly of analogues compounds capable of hydrogen bonding have a high likelihood of being altered even in the presence of a nonactivated iodine atom.

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“…31 Hz, 2H). 13 Synthesis of N-(5-Bromopyridin-2-yl)benzamide. 2-Amino-5bromopyridine (1.90 g, 11.0 mmol) was dissolved in 50 mL of pyridine and cooled in an ice bath.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Section: ■ Experimental Sectionmentioning

confidence: 99%

Mapping out the Relative Influence of Hydrogen and Halogen Bonds in Crystal Structures of a Family of Amide-Substituted Pyridines

Abeysekera

Day

Sinha

et al. 2020

Crystal Growth & Design

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“…DSC takes the first preference for rapid analysis of incompatibility of the pharmaceutical mixture Thus, in this current research DSC (SDT.Q600, USA) is a thermoanalytical method used to study interaction between active drug and excipients. The pure drug,superdisintegrants, and its mixtures were scanned individually to confirm compatibility [20,21].…”

Section: Dsc Studymentioning

confidence: 99%

Atenolol And Nifedipine Combination Is Better Than Monotherapy: A New Era In Novel Drug Delivery For Hypertension

Swapna¹,

Maheswaramma²,

Reddy³

2021

JUSST

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Hypertension is considered a major health problems globally affect millions of patient.Various study confirms that single drug treatment usually is not adequate to achieve blood pressure goal in most hypertensive patients.In this regard,consideration is given to combination therapy, which offers the potential advantages towards minimizing hypertension in a rapid manner and produces lower adverse effects.SLTs (Sublingual tablets) provides immediate action to enhanced absorption and bioavailability rate. Sublingual tablets are absorbed within the mucus membrane and directly reach in blood systemic circulation. The objective of this ongoing research focused on theatenolol (ATN)and nifedipine (NIF) combined drug deliveryin emergency condition of hypertension. Direct compression technique is used to formulate SLTsby taking different types and concentrations of superdisintegrantsCroscarmellose sodium (CCS) and Crospovidone (CP). Sublimating agents like camphor (CM) and thymol (TY)) also added for better result. FTIR and DSC analysis confirms the ccompatibility results between drug and superdisintegrants.Formulated tablets are evaluated for different parameters and found satisfactory. Formulation F6 considered as the best formulation. The disintegration shows 13 sec and dissolution profile shows 97.36% drug release at 10 min. Formulation F6 shows better pharmacokinetic activity and antihypertensive activity in compare to pure drug and marketed formulation.A combination of ATN and NIF produces rapid disintegration and dissolution property during an emergency and is a lifesaving approach in hypertension treatment.

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“…The efficiency, safety, quality, and stability of pharmaceutical dosage forms, which are the result of the active pharmaceutical ingredients (API) combination with excipients, are of major importance in the drug development process. A proper formulation design involves the selection of suitable excipients; although these pharmacologically-inactive substances are considered inert molecules, during the formulation stage and/or under storage of final product, interactions may occur even in solid state, leading to a diminution of concentration of API [ 32 , 33 , 34 ]. Potential interactions between an API and excipients have to be evaluated because the incompatibilities between the components of a dosage form can affect the bioavailability, stability, potency, and safety of drug products [ 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

Risperidone/Randomly Methylated β-Cyclodextrin Inclusion Complex—Compatibility Study with Pharmaceutical Excipients

et al. 2021

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Risperidone (RSP) is an atypical antipsychotic drug used in treating schizophrenia, behavioral, and psychological symptoms of dementia and irritability associated with autism. The drug substance is practically insoluble in water and exhibits high lipophilicity. It also presents incompatibilities with pharmaceutical excipients such as magnesium stearate, lactose, and cellulose microcrystalline. RSP encapsulation by randomly methylated β-cyclodextrin (RM-β-CD) was performed in order to enhance drug solubility and stability and improve its biopharmaceutical profile. The inclusion complex formation was evaluated using thermal methods, powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier transform infrared (UATR-FTIR), UV spectroscopy, and saturation solubility studies. The 1:1 stoichiometry ratio and the apparent stability constant of the inclusion complex were determined by means of the phase solubility method. The compatibility between the supramolecular adduct and pharmaceutical excipients starch, anhydrous lactose, magnesium stearate, and cellulose microcrystalline was studied employing thermoanalytical tools (TG-thermogravimetry/DTG-derivative thermogravimetry/HF-heat flow) and spectroscopic techniques (UATR-FTIR, PXRD). The compatibility study reveals that there are no interactions between the supramolecular adduct with starch, magnesium stearate, and cellulose microcrystalline, while incompatibility with anhydrous lactose is observed even under ambient conditions. The supramolecular adduct of RSP with RM-β-CD represents a valuable candidate for further research in developing new formulations with enhanced bioavailability and stability, and the results of this study allow a pertinent selection of three excipients that can be incorporated in solid dosage forms.

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Solid-state compatibility studies of Ketoconazole-Fumaric acid co-crystal with tablet excipients

Cited by 13 publications

References 31 publications

Mapping out the Relative Influence of Hydrogen and Halogen Bonds in Crystal Structures of a Family of Amide-Substituted Pyridines

Mapping out the Relative Influence of Hydrogen and Halogen Bonds in Crystal Structures of a Family of Amide-Substituted Pyridines

Atenolol And Nifedipine Combination Is Better Than Monotherapy: A New Era In Novel Drug Delivery For Hypertension

Risperidone/Randomly Methylated β-Cyclodextrin Inclusion Complex—Compatibility Study with Pharmaceutical Excipients

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