Strides Pharma's Generic Polyethylene Glycol 3350; Potassium Chloride; Sodium Bicarbonate; Sodium Chloride; Sodium Sulfate Anhydrous Receives Approval in US
Solid dispersion formulations made of itraconazole (ITZ) and Soluplus® (polyethylene glycol, polyvinyl acetate and polyvinylcaprolactame-based graft copolymer abbreviated SOL) were produced using hot melt extrusion. Since ITZ possesses a water solubility of less than 1 ng/mL, the aim of this work was to enhance the aqueous solubility of ITZ, and thereby improve its bioavailability. The three formulations consisted of a simple SOL/ITZ amorphous solid dispersion (ASD), an optimized SOL/ITZ/AcDiSol® (super-disintegrant) ASD and an equimolar inclusion complex of ITZ in hydroxypropyl-?-cyclodextrin (substitution degree = 0.63, CD) with SOL. The three formulations were compared in vitro and in vivo to the marketed product Sporanox®. The in vitro enhancement of dissolution rate was evaluated using a biphasic dissolution test. In vitro dissolution results showed that all three formulations had a higher percentage of ITZ released than Sporanox® with the following ranking: SOL/ITZ/CD > SOL/ITZ/AcDiSol® > SOL/ITZ > Sporanox®. The bioavailability of these four formulations was evaluated in rats. The bioanalytical method was optimized so that only 10 ?L of blood was withdrawn from the rats using specific volumetric absorptive microsampling devices. This enabled to keep the same rats during the whole study, which was in accordance with the Three Rs rules (reduction, refinement and replacement). Furthermore, this technique allowed the suppression of inter-individual variability. Higher Cmax and AUC were obtained after the administration of all three formulations compared to the levels after the use of Sporanox® as follows: SOL/ITZ/AcDiSol® > SOL/ITZ/CD > SOL/ITZ > Sporanox®. The inversion in the ranking between SOL/ITZ/CD and SOL/ITZ/AcDiSol® made impossible the establishment of an in vitro–vivo correlation. Indeed, very different release rates were obtained in vitro and in vivo for the two optimized formulations. These results suggest that ITZ would be protected inside the core of the SOL micelles even during the absorption step at the intestine, while some agents present in the intestinal fluids could displace ITZ from the hydrophobic cavity of CD by competition.
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Polyethylene oxide (PEO) has been extensively used as an extended-release excipient in matrix tablets due to its extraordinarily safe, stable, soluble, swellable and erodible properties. The present study aimed to develop once-daily sustained-release tablets using PEO for a highly water-soluble drug, diltiazem hydrochloride (DH), the clinical application of which is limited because of its short half-life in vivo. However, the prophase study demonstrated that the use of PEO alone could only retard the drug release to 8 h. Thus, we proposed its combined use with chitosan/sodium alginate and formulated ternary matrix tablets by direct compression, in the hope of further extending the release of DH.
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Strides, Torrent Pharma, Glenmark, Lupin Gain on USFDA Nod
Strides Arcolab gets USFDA nod for bowel-cleansing medicine