Study the influence of formulation process parameters on solubility and dissolution enhancement of efavirenz solid solutions prepared by hot-melt extrusion: a QbD methodology.

The current study investigates the dissolution rate performance of amorphous solid solutions of a poorly water-soluble drug, efavirenz (EFV), in amorphous Soluplus® (SOL) and Kollidon® VA 64 (KVA64) polymeric systems. For the purpose of the study, various formulations with varying drug loadings of 30, 50, and 70% w/w were developed via hot-melt extrusion processing and adopting a Box-Behnken design of experiment (DoE) approach. The polymers were selected based on the Hansen solubility parameter calculation and the prediction of the possible drug-polymer miscibility. In DoE experiments, a Box-Behnken factorial design was conducted to evaluate the effect of independent variables such as Soluplus® ratio (A1), HME screw speed (A2), and processing temperature (A3), and Kollidon®VA64 ratio (B1), screw speed (B2), and processing temperature (B3) on responses such as solubility (X1 and Y1) and dissolution rate (X2 and Y2) for both ASS [EFV:SOL] and BSS [EFV:KVA64] systems. DSC and XRD data confirmed that bulk crystalline EFV transformed to amorphous form during the HME processing. Advanced chemical analyses conducted via 2D COSY NMR, FTIR chemical imaging, AFM analysis, and FTIR showed that EFV was homogenously dispersed in the respective polymer matrices. The maximum solubility and dissolution rate was observed in formulations containing 30% EFV with both SOL and KVA64 alone. This could be attributed to the maximum drug-polymer miscibility in the optimized formulations. The actual and predicted values of both responses were found precise and close to each other.

Toward tunable amphiphilic copolymers via CuAAC click chemistry of oligocaprolactones onto starch backbone.

Starch-based tunable amphiphilic copolymers are easily obtained by grafting polycaprolactone chains via 1,3 dipolar Copper-Catalyzed Azide-Alkyne Cycloaddition (click chemistry CuAAC), starting from propargylated starch and azido oligocaprolactones with different chain lengths as the precursors. The copolymers are characterized by (1)H and (13)C NMR, from which a degree of substitution of starch can tentatively be deduced. Besides these bulk characterizations, the surface of the functionalized starch is also characterized by XPS which confirms the triazole formation, particularly through the deconvolution of the N 1s peak, and by ToF-SIMS which, not only confirms the surface modification, but also highlights the disappearance of the Cu(+) cations. The solubility and swelling behaviours of these copolymers have been investigated, which clearly show the dependence both on the solvent and the PCL chain length. These investigations highlight the swelling dependence on the δd component of the Hansen solubility parameter of solvents. Finally, at low concentration, they present the capacity to organize themselves in aggregates in aqueous solutions, as seen from TEM and DLS investigations.

Strategies for the chemoenzymatic preparation of optically active 1-alkyn-3-ols.

A series of (R)- and (S)-1-alkyn-3-ols, chiral building units for the synthesis of leukotrienes and pheromones, were prepared via enantioselective hydrolysis of their racemic esters. While the majority of biocatalysts employed (lipases, fermenting or freeze-dried microorganisms) failed in discriminating between enantiomers, lyophilized cells of baker's yeast (Saccharomyces cerevisiae Hansen) gave (S)-1-alkyn-3-ols and their corresponding (R)-esters with greater than 90% e.e.