Studies on effect of hydrophilic polymers on physicochemical properties of itraconazole cocrystals

Shete, Amol; Murthy, Srinivasa; Thorat, Bhagyashri; Yadav, Adhikrao Vyankatrao; Sajane, Sachin; Sakhare, Sfurti; Doijad, Rajendra

doi:10.1016/j.fjps.2017.04.005

Cited by 7 publications

(4 citation statements)

References 9 publications

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“…5,6 In order to maximise the potential of cocrystals, it is critical to include inhibitors in a formulation to prevent or delay the precipitation of the parent drug during dissolution. [7][8][9][10][11][12][13] Although polymeric crystallization inhibitors have been extensively studied in many other systems, in particular amorphous solid dispersions, 14,15 such studies are still rare for cocrystal based formulations. In a recent study, we have found that the competition of intermolecular hydrogen bonding among drug/coformer, drug/polymer, and coformer/polymer was a key factor responsible for maintaining the supersaturation through nucleation inhibition and crystal growth modification in a supersaturated cocrystal solution with a pre-dissolved polymer.…”

Section: Introductionmentioning

confidence: 99%

“…Pharmaceutical cocrystals have attracted remarkable interests for enhancing solubility and dissolution rates of poorly water-soluble drugs. − A highly supersaturated solution concentration, which is significantly greater than the equilibrium saturation concentration of the parent drug, can be generated due to rapid dissolution of cocrystals, which is a key requirement for improved drug oral absorption . However, maintaining such a supersaturated state is challenging because of the tendency for rapid precipitation of a more stable form of the parent drug during dissolution. , In order to maximize the potential of cocrystals, it is critical to include inhibitors in a formulation to prevent or delay the precipitation of the parent drug during dissolution. − Although polymeric crystallization inhibitors have been extensively studied in many other systems, in particular amorphous solid dispersions, , such studies are still rare for cocrystal based formulations. In a recent study, we have found that the competition of intermolecular hydrogen bonding among drug/coformer, drug/polymer, and coformer/polymer was a key factor responsible for maintaining the supersaturation through nucleation inhibition and crystal growth modification in a supersaturated cocrystal solution with a predissolved polymer .…”

Section: Introductionmentioning

confidence: 99%

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Insight into Flufenamic Acid Cocrystal Dissolution in the Presence of a Polymer in Solution: from Single Crystal to Powder Dissolution

et al. 2017

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Effects of three polymers, polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and copolymer of vinyl pyrrolidone/vinyl acetate (PVP-VA), on the dissolution behaviour of the cocrystals of flufenamic acid with theophylline (FFA-TP CO) and nicotinamide (FFA-NIC CO) were investigated at multiple length scales. At the molecular level, the interactions of crystal surfaces with a polymer were analysed by observing etching pattern changes using atomic force microscopy. At the macroscopic scale, dissolution rates of particular faces of a single crystal were determined by measurement of the physical retreat velocities of the faces using optical light microscopy. In the bulk experiments, the FFA concentration in a dissolution medium in the absence or presence of a polymer was measured under both sink and non-sink conditions. It has been found that the dissolution mechanisms of FFA-TP CO are controlled by the defect sites of the crystal surface and by precipitation of the parent drug FFA as individual crystals in the bulk fluid. In contrast, the dissolution mechanisms of FFA-NIC CO are controlled by surface layer removal and by a surface precipitation mechanism, where the parent drug FFA precipitates directly onto the surface of the dissolving cocrystals. Through controlling the dissolution environment by pre-dissolving a polymer, PVP or PVP-VA, which can interact with the crystal surface to alter its dissolution properties, improved solubility and dissolution rates of FFA-TP CO and FFA-NIC CO have been demonstrated.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Insight into Flufenamic Acid Cocrystal Dissolution in the Presence of a Polymer in Solution: from Single Crystal to Powder Dissolution

et al. 2017

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“…But the double ring structure in SAC molecule may generate larger steric hindrance. PVP may interfere the intermolecular interactions between CBZ and SAC but is not essential to disturb the formation of the CBZ-SAC cocrystal structure [ 43 ]. On the contrary, the addition of PVP induced the formation of CBZ-SAC cocrystal.…”

Section: Resultsmentioning

confidence: 99%

Preparation and Characterization of Carbamazepine Cocrystal in Polymer Solution

et al. 2017

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In this study, we attempted to prepare carbamazepine (CBZ) cocrystal through the solution method in ethanol-water solvent mixture (volume ratio 1:1) and polyvinyl pyrrolidone (PVP) solution. Nicotinamide (NIC) and saccharin (SAC) were selected as cocrystal coformers. Cocrystal screening products were characterized by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Powder X-ray Diffraction (PXRD) techniques. Characterization results show that in ethanol-water solvent mixture, pure CBZ-NIC cocrystal can be prepared, while CBZ-SAC cocrystal cannot be obtained. The addition of PVP can inhibit CBZ-NIC cocrystal formation and facilitate CBZ-SAC cocrystal formation.

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“…ITZ is a lipophilic, crystalline compound with limited water solubility and a molecular weight of approximately 705.6 g/mol. It exhibits a pKa of about 3.7 and a logP (partition coefficient) value of around 6.8, reflecting its hydrophobic nature, which can impact its oral absorption and formulation challenges [3]. ITZ shows dose-dependent toxicity, particularly when used at high doses or for extended periods.…”

Section: Introductionmentioning

confidence: 99%

Itraconazole Loaded Biosurfactin Micelles with Enhanced Antifungal Activity: Fabrication, Evaluation and Molecular Simulation

Usman,

Farooq,

Wani

et al. 2023

Antibiotics

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Itraconazole (ITZ) is a broad-spectrum antifungal for superficial subcutaneous and systemic fungal infections. This study aimed to enhance the antifungal activity of ITZ using surfactin A (SA), a cyclic lipopeptide produced by the SA-producing Bacillus strain NH-100, possessing strong antifungal activity. SA was extracted, and ITZ-loaded SA micelles formulations were prepared via a single-pot rinsing method and characterized by particle size, zeta potential, and infrared spectroscopy. In vitro dissolution at pH 1.2, as well as hemolysis studies, was also carried out. The fabricated formulations were stable and non-spherical in shape, with an average size of about 179 nm, and FTIR spectra depicted no chemical interaction among formulation components. ITZ-loaded micelles showed decreased hemolysis activity in comparison to pure ITZ. The drug released followed the Korsmeyer–Peppas model, having R2 0.98 with the diffusion release mechanism. In an acidic buffer, drug release of all prepared formulations was in the range of 73–89% in 2 h. The molecular simulation showed the outstanding binding and stability profile of the ITZ-SA complex. The aromatic ring of the ITZ mediates a π-alkyl contact with a side chain in the SA. It can be concluded that ITZ-loaded micelles, owing to significant enhanced antifungal activity up to 6-fold due to the synergistic effect of SA, can be a promising drug delivery platform for delivery of poorly soluble ITZ.

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Studies on effect of hydrophilic polymers on physicochemical properties of itraconazole cocrystals

Cited by 7 publications

References 9 publications

Insight into Flufenamic Acid Cocrystal Dissolution in the Presence of a Polymer in Solution: from Single Crystal to Powder Dissolution

Insight into Flufenamic Acid Cocrystal Dissolution in the Presence of a Polymer in Solution: from Single Crystal to Powder Dissolution

Preparation and Characterization of Carbamazepine Cocrystal in Polymer Solution

Itraconazole Loaded Biosurfactin Micelles with Enhanced Antifungal Activity: Fabrication, Evaluation and Molecular Simulation

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