Preparation and comparison of binary and ternary inclusion complexes of aripiprazole using L-arginine/lysine and MßCD/HPßCD by using different molar ratios.

Aripiprazole (ARI), an antipsychotic having low solubility and stability. To overcome this, formation of binary and ternary using inclusion complexes of Methyl-ß-cyclodextrin (MßCD) /Hydroxy propyl beta cyclodextrin (HPßCD) and L-Arginine (ARG)/ Lysine (LYS) are analyzed by dissolution testing and phase stability study along with their complexation efficacy and solubility constants made by physical mixing. Inclusion complexes with ARG were better than LYS and prepared by solvent evaporation and lyophilization method as well. They are characterized by Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (AT-FTIR), X-ray powder diffractometry (XRD), Differential Scanning Calorimetry (DSC), Scanning electron microscopy (SEM) and Thermal gravimetric analysis (TGA). The bond shifting in AT-FTIR confirmed the molecular interactions between host and guest molecules. The SEM images also confirmed a complete change of drug morphology in case of ternary inclusion complexes prepared by lyophilization method for both the polymers. ARI: MßCD: ARG when used in the specific molar ratio of 1:1:0.27 by prepared by lyophilization method has 18 times best solubility while ARI:HPßCD:ARG was 7 times best solubility than pure drug making MßCD a better choice than HPßCD. Change in the molar ratio will cause loss of stability or solubility. Solvent evaporation gave significant level of solubility but less stability.

Enhanced Solubility and Stability of Aripiprazole in Binary and Ternary Inclusion Complexes Using Hydroxy Propyl Beta Cyclodextrin (HPßCD) and L-Arginine.

The low water solubility of an active pharmaceutical ingredient (aripiprazole) is one of the most critical challenges in pharmaceutical research and development. This antipsychotic drug has an inadequate therapeutic impact because of its minimal and idiosyncratic oral bioavailability to treat schizophrenia. The main objective of this study was to improve the solubility and stability of the antipsychotic drug aripiprazole (ARP) via forming binary as well as ternary inclusion complexes with hydroxypropyl-ß-cyclodextrin (HPßCD) and L-Arginine (LA) as solubility enhancers. Physical mixing and lyophilization were used in different molar ratios. The developed formulations were analyzed by saturation solubility analysis, and dissolution studies were performed using the pedal method. The formulations were characterized by FTIR, XRD, DSC, SEM, and TGA. The results showcased that the addition of HPßCD and LA inclusion complexes enhanced the stability, in contrast to the binary formulations and ternary formulations prepared by physical mixing and solvent evaporation. Ternary formulation HLY47 improved dissolution rates by six times in simulated gastric fluid (SGF). However, the effect of LA on the solubility enhancement was concentration-dependent and showed optimal enhancement at the ratio of 1:1:0.27. FTIR spectra showed the bond shifting, which confirmed the formation of new complexes. The surface morphology of complexes in SEM studies showed the rough surface of lyophilization and solvent evaporation products, while physical mixing revealed a comparatively crystalline surface. The exothermic peaks in DSC diffractograms showed diminished peaks previously observed in the diffractogram of pure drug and LA. Lyophilized ternary complexes displayed significantly enhanced thermal stability, as observed from the thermograms of TGA. In conclusion, it was observed that the preparation method and a specific drug-to-polymer and amino acid ratio are critical for achieving high drug solubility and stability. These complexes seem to be promising candidates for novel drug delivery systems development.

Improved solubility and stability of aripiprazole in binary and ternary inclusion complexes using methyl-ß-cyclodextrin and L-arginine.

The aim of this study was to improve the solubility of aripiprazole (ARP) by fabricating binary and ternary inclusion complexes with methyl-ß-cyclodextrin (MßCD) and L-Arginine (LA). Physical mixing and lyophilization were used in the following molar ratios: 1:1, 1:2.5, 1:4, 1:9, 1:1:1, 1:1:0.27, 1:4:1, 1:9:1, 1:3.6:3.6. The developed formulations were analyzed by solubility and dissolution. They were characterized by FTIR, XRD, DSC, SEM and TGA. Ternary formulations prepared by the lyophilization method showed improved dissolution rates in simulated gastric fluid (SGF). The results showcased that the addition of MßCD and LA in inclusion complexes enhanced the solubility and decreased crystallinity. The amorphous nature of Aripiprazole in lyophilization was confirmed by XRD diffractograms. Drug release was dominated by the first-order kinetics (R2 = 0.9932) with the Fickian type of diffusion mechanism (n<0.450). LY18, LY19, LY20 and LY21 have the highest solubility (30, 35, 43 and 48 times higher than the pure drug respectively). Furthermore, it was observed that the method of preparation, as well as a specific drug to polymer and amino acid ratio, are critical for achieving high drug solubility and stability. These complexes appeared to be a promising product for the development of new drug delivery systems.