The Controlled Preparation of a Carrier-Free Nanoparticulate Formulation Composed of Curcumin and Piperine Using High-Gravity Technology. Pharmaceutics Carrier-free nanoparticulate formulations are an advantageous platform for the oral administration of insoluble drugs with the expectation of improving their bioavailability. However, the key limitation of exploiting carrier-free nanoparticulate formulations is the controlled preparation of drug nanoparticles on the basis of rational prescription design. In the following study, we used curcumin (Cur) and piperine (Pip) as model water-insoluble drugs and developed a new method for the controlled preparation of carrier-free drug nanoparticles via multidrug co-assembly in a high-gravity environment. Encouraged by the controlled regulation of the nucleation and crystal growth rate of high-gravity technology accomplished by a rotating packed bed, co-amorphous Cur-Pip co-assembled multidrug nanoparticles with a uniform particle size of 130 nm were successfully prepared, exhibiting significantly enhanced dissolution performance and in vitro cytotoxicity. Moreover, the hydrogen bonding interactions between Cur and Pip in nanoparticles provide them with excellent re-dispersibility and storage stability. Moreover, the oral bioavailability of Cur was dramatically enhanced as a result of the smaller particle size of the co-assembled nanoparticles and the effective metabolic inhibitory effect of Pip. The present study provides a controlled approach to preparing a carrier-free nanoparticulate formulation through a multidrug co-assembly process in the high-gravity field to improve the oral bioavailability of insoluble drugs. 10.3390/pharmaceutics16060808

Computational-Based Polyphenol Therapy for Nonsmall Cell Lung Cancer: Naringin Coamorphous Systems for Solubility and Bioavailability Enhancement. Molecular pharmaceutics In this research, we utilized molecular simulations to create co-amorphous materials (CAMs) of ceritinib (CRT) with the objective of improving its solubility and bioavailability. We identified naringin (NRG) as a suitable co-former for CRT CAMs based on binding energy and intermolecular interactions through computational modeling. We used the solvent evaporation method to produce CAMs of CRT and NRG, expecting to enhance both solubility and bioavailability simultaneously. The solid-state characterization using techniques like differential scanning calorimeter, X-ray powder diffraction, and Fourier-transform infrared spectroscopy affirmed the formation of a single amorphous phase and the presence of intermolecular interactions between CRT and NRG in the CAMs. These materials remained physically stable for up to six months under dry conditions at 40 °C. Moreover, the CAMs demonstrated significant improvements in the solubility and dissolution of CRT (specifically in the ratio CRT:NRG 1:2). This, in turn, led to an increase in cytotoxicity, apoptotic cells, and G0/G1 phase inhibition in A549 cells compared to CRT alone. Furthermore, CRT permeability is also improved twofold, as estimated by the everted gut sac method. The enhanced solubility of CAMs also positively affected the pharmacokinetic parameters. When compared to the physical mixture, the CAMs of CRT:NRG 2:1 exhibited a 2.1-fold increase in CRT exposure (AUC) and a 2.4-fold increase in plasma concentration (). 10.1021/acs.molpharmaceut.4c00303

Breaking barriers: enhancing solubility and dissolution of efonidipine using co-amorphous formulations. Naunyn-Schmiedeberg's archives of pharmacology The study aims to enhance the solubility and dissolution characteristics of efonidipine hydrochloride ethanolate (EFD), an antihypertensive drug, through the co-amorphous approach. Hypertension is a prevalent chronic condition characterized by consistently elevated blood pressure. Efonidipine, a BCS class II drug, has high permeability but low solubility, limiting its therapeutic effectiveness. Amorphization, which disrupts the crystal lattice of crystalline medications, can significantly enhance drug solubility and dissolution rates. Co-amorphous systems of EFD were prepared using solvent evaporation, ball milling, and liquid-assisted grinding methods. The drug and co-former were used in a different ratio, a stoichiometric proportion known for forming stable amorphous phases. The in vitro dissolution of the co-amorphous form was evaluated and compared with the pure crystalline form of EFD. The co-amorphous system of EFD with benzoic acid demonstrated significantly higher dissolution rates in vitro compared to the pure drug. PXRD analysis confirmed the transformation from a crystalline to an amorphous state, indicated by the disappearance of sharp peaks characteristic of the crystalline form. The resultant co-amorphous system exhibited dissolution properties. The co-amorphous approach effectively improved the solubility and dissolution of efonidipine hydrochloride ethanolate. Benzoic acid, as a co-former, facilitated the formation of a stable amorphous phase, thereby enhancing the drug's dissolution rate. The developed a co-amorphous system of EFD with benzoic acid, significantly enhancing its dissolution characteristics. PXRD analysis confirmed the amorphous nature and improved stability of the co-amorphous form, indicating its potential for better therapeutic efficacy in hypertension management. 10.1007/s00210-024-03606-6

A drug-drug co-amorphous system for highly improved solubility of breviscapine: an experimental and computational study. Scientific reports Drug-drug co-amorphous systems are a promising approach to improve the aqueous solubility of poorly water-soluble drugs. This study explores the combination of breviscapine (BRE) and matrine (MAT) form an amorphous salt, aiming to synergistically enhance the solubility and dissolution of BRE. In silico analysis of electrostatic potential and local ionization energy were conducted on BRE-MAT complex to predict the intermolecular interactions, and solvent-free energies were calculated using thermodynamic integration and density functional theory. The co-amorphous mixture, prepared by solvent evaporation, was characterized using various analytical techniques, including polarized microscopy, differential scanning calorimetry, and powder X-ray diffraction, confirming its amorphous nature. Fourier transform infrared spectroscopy and molecular dynamic simulations revealed strong hydrogen bonding, with a proton transfer from the carboxyl group of BRE to the tertiary amine nitrogen of MAT. The resulting co-amorphous salt demonstrated substantial solubility improvement (> 8000-fold in water) and enhanced in vitro dissolution of BRE. The study also confirmed that the co-amorphous salt maintained physical stability at 40 °C and 75% relative humidity over 6 months. These findings provide a viable strategy for developing drug-drug co-amorphous formulations to enhance solubility and stability, with significant potential for pharmaceutical applications. 10.1038/s41598-024-82524-2