Pharmaceutical cocrystals: An overview

Qiao, Ning; Li, Mingzhong; Schlindwein, Walkiria; Malek, Nazneen; Davies, Angela M.; Trappitt, Gary

doi:10.1016/j.ijpharm.2011.07.037

Cited by 576 publications

(447 citation statements)

References 91 publications

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“…[1][2][3] 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. 4 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.…”

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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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%

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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“…The effect on the physicochemical properties of the API is dependent on the available coformer [16,24,27,28] . Another unique advantage of cocrystals over the more common salts is that cocrystals can be made for non-ionisable APIs as well as for those complex drugs which have sensitive functional groups that may not survive the harsh reaction conditions of strong acids or bases [12,28] . There are several other main advantages behind the formulating the cocrystals.…”

Section: Advantages Of Cocrystalsmentioning

confidence: 99%

“…Pharmaceutical cocrystals are structurally different to their bulk forms; it is possible to patent cocrystals of existing APIs as a new crystal form. Different formulations of pharmaceutical cocrystals are available in the market such as Viagra (Pfizer) to treat erectile dysfunction and pulmonary arterial hypertension, Entresto (Novartis) for treatment of chronic heart failure and some others under clinical developments [12,14,16,24,28] . Pharmaceutical cocrystals can enhance the physicochemical properties of drugs such as melting point, tabletability, solubility, stability, bioavailability, permeability and these properties are highlighted here with suitable examples.…”

Section: Advantages Of Cocrystalsmentioning

confidence: 99%

“…With the help of K eu , Serajuddin described the cocrystals solubility ratio and solution chemistry by using a set of more than 40 cocrystals and solvent combinations [43] . In one study, equations that describe cocrystal solubility in term of product solubility, cocrystal component ionization constants, and solution pH were derived for cocrystals with acidic, basic, amphoteric and zwitterionic components [12,44] .…”

Section: Solubilitymentioning

confidence: 99%

“…Ionic cocrystals were contained ionized coformers in a stoichiometric ratio and formed by charge assisted hydrogen bonds and/or coordination bonds [11] . Pharmaceutical cocrystals have been defined as cocrystals, which contained an API as one component and another component as a coformer in a stoichiometric ratio [12] .…”

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Pharmaceutical Cocrystals: An Overview

Kumar¹,

Nanda²

2017

pharmaceutical-sciences

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Preclinical and Clinical Studies

Brewster¹,

Verreck²,

Bevernage³

et al. 2015

Pharmaceutical Sciences Encyclopedia

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Contemporary drug pipelines are increasingly populated with difficult‐to‐formulate drug substances. Amorphous solid dispersions can increase drug dissolution rate by reducing the effective drug particle size through its dispersion in the matrix. Based on the theorized way of working of amorphous solid dispersions, one of the most important design elements is their ability to dissolve and supersaturate. This is initially assessed in vitro through the use of dissolution protocols especially set up for that purpose. A number of in vivo assessments of the potential utility of amorphous solid dispersions have been completed using various animal models. Clinical assessments to investigate itraconazole supersaturation (indirectly) have also been completed. Itraconazole is a widely studied compound in this context with numerous in vitro , in vivo , and clinical evaluations completed. Useful preclinical and clinical models for assessing solid dispersion fitness will contribute to the drug development process.

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Pharmaceutical cocrystals: An overview

Cited by 576 publications

References 91 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

Pharmaceutical Cocrystals: An Overview

Preclinical and Clinical Studies

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