In recent times the integration of the nanocrystal as well as the cocrystal based approach into the single drug formulation as nano cocrystals has been gaining wide scope of interest Nano cocrystal based formulation approaches have some unique properties and exhibit some advantages like improved chemical stability saturation solubility dissolution rate and bioavailability by some research groups Nano cocrystals have been an area of interest as limited research has been done and reported in the field of pharmaceuticals Researchers have attempted to produce the nano cocrystals by top down and bottom up approaches successfully Nano cocrystal formulations are currently being explored for solubility enhancement improved physical properties and bioavailability over the other enabling technologies for the poorly water drugs Based on the outcomes by many research groups an overview of the method of preparation and properties have been described below In 2010 Sander et al 2 reported ultrasound assisted antisolvent precipitation method in presence of surfactant Span85 as a strategy for crystal engineering of nano sized cocrystals Caffeine 2 4 dihydroxybenzoic acid monohydrate system was selected as the model cocrystal The cocrystal components were dissolved in common and different solvent s and injected into anti solvent under ultrasonic radiation at 0º C to yield nano cocrystals Studies of particle size by Dynamic light scattering DLS and surface morphology by SEM showed that the cocrystal obtained by use of the two solvent method produced nano sized cocrystals with less polydispersity index PDI within nanometer particle size range In 2013 De Smet et al 2 reported Itraconazole ITRA adipic acid nano cocrystals prepared by wet milling method
The physical mixture of itraconazole dicarboxylic acid coformers maleic adipic succinic and glutaric acid were milled in presence of surfactant Tween 80 to form a stable nano cocrystal suspension The obtained nanosuspension was measured for the size PDI and the Itraconazole adipic acid cocrystals were selected The prepared nanosuspension for the ease of administration nanosuspension was converted to solid dosage form by spray drying and bead coating Dissolution test were performed for at pH 1 and pH 3 for the different nano cocrystal formulations nanosuspension spray dried powder ITRA SD2 and layered beads ITRA BL1 with respected to the reference formulation Sporanox On oral administration of different ITRA nano cocrystal formulations to dogs containing 200mg equivalent ITRA with Sporanox as the reference formulation the bioavailability and pharmacokinetic parameters were assed At pH 1 the dissolution of the nano cocrystal formulation have a higher dissolution rate with respect to the reference formulation but at pH 3 for both nano cocrystal based formulations and Sporanox indicating a pH dependent release of ITRA There was no significant difference in bioavailability between different formulations this can be due to the variable pH of dog the pharmacokinetic results are more related to the in vitro results at pH 3 indicating an incomplete release of the nano cocrystals but still faster compared to the release of reference formulation In 2014 Spitzer et al reported Spray flash evaporation for the continuous production of pharmaceutical and energeitc micro and nanocrystals In 2015 karashima et al reported cocrystals of carbamazepine saccharin CBZ SAC indomethacine saccharin IMC SAC and furosemide caffine FAS CAF by wet media milling
The wet milling was perfomed in presence of surfactant sodium dodecyl sulphate and stabilizers hydroxypropyl methylcellulose and the nano cocrystals suspension were obtained with particle size less than 300 nm The nano cocrystal suspensions were subjected to stability for 1 and 3 months stability In stability study it is observed that the prepared FSD CAF CBZ SAC and IMC SAC nano cocrystal suspensions were physically and chemically stable for at least one month at 5 and 25 ºC The dissolution study indicated that the nanocrystal suspensions had a superior dissolution rate and saturation solubility compared to the pure nanocrystals and cocrystals In 2016 Liu et al reported generation of myricetin nicotinamide MYR NIC nanococrystals by top down and bottom up technologies In top down approach nano cocrystals were obtained by neat grinding of the cocrystal components in stoichiometric ratio MYR NIC 1 2 In bottom up approach the nano cocrystals were obtained by combined use of ternary phase diagram solution method and Ultrasound assisted solution crystallization The cocrystals obtained by top down method had particle size within nano meter range with high polydispersity The cocrystals obtained by the bottom up have 200 nm with uniform distribution The dissolution profiles of nano cocrystal were found to be superior with respect to the normal cocrystal particles It is inferred that the dissolution properties of the nano cocrystals prepared by solution method were superior over that of the nano cocrystal prepared by grinding approach In 2017 Huang et al reported the generation of Phenazopyridine phthalimide nano cocrystals by bottom up approach The Phenazopyridine phthalimide cocrystal were prepared to address the hygroscopicity of marketed salt form of Phenazopyridine but there was decrease in the aqueous solubility Particle size reduction to nanometre range of the prepared cocrystal was hypothesised to enhance the dissolution rate and bioavailability Nano sized cocrystals of Phenazopyridine phthalimide were prepared by ultrasound assisted antisolvent precipitation method in presence of surfactant SDS Top down based approach like wet milling has been used for the production of the nanosized cocrystal in the presence of surfactants and stabilizers
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