The Study of Deep Eutectic Solvent Based on Choline Chloride and L-(+)-Tartaric Acid Diethyl Ester for Transdermal Delivery System.

Deep eutectic solvents (DESs) based on choline chloride (C) and L-(+)-tartaric acid diethyl ester (L) were prepared and used in transdermal drug delivery system (TDDS). The internal chemistry structure including the formation and changes of hydrogen bonds of choline chloride and L-(+)-tartaric acid diethyl ester DES was characterized via attenuated total reflection Fourier transform infrared (ATR-FTIR) and 1H nuclear magnetic resonance (1H NMR) spectroscopy. The stoichiometric ratio of choline chloride to L-(+)-tartaric acid diethyl ester as well as water content affected the viscosity, glass transition temperature (Tg), and drug solubility of the DES. The viscosity and glass transition temperature of the DES (CL14) prepared at the ratio of 1:4 of choline chloride to L-(+)-tartaric acid diethyl ester were 1.19 Pa·s and - 44.01°C, respectively, and decreased to 0.10 Pa·s and - 55.31°C when 10% water (CL1410) was added. Taking diclofenac diethylamine (DDEA), the nonsteroidal anti-inflammatory drug as model, drug solubility was as high as 60 mg/ml and 250 mg/ml in CL14 and CL1410, respectively. The cumulative amount of DDEA was 4.63 ± 2.67 µg/cm2 and 15.27 ± 4.63 µg/cm2 for CL14 and CL1410, respectively, at 8 h. The mechanism of percutaneous permeability by the DES may be the disturbance of stratum corneum (SC) lipids as well as changes in the protein conformations. CL14 and CL1410 were also verified as low-cytotoxic and nonirritant. Therefore, the DESs studied are promising to be used in drug solubilization enhancement and transdermal drug delivery system.

Overview of nanoparticulate strategies for solubility enhancement of poorly soluble drugs.

Poor aqueous solubility and poor bioavailability are major issues with many pharmaceutical industries. By some estimation, 70-90% drug candidates in development stage while up-to 40% of the marketed products are poorly soluble which leads to low bioavailability, reduced therapeutic effects and dosage escalation. That's why solubility is an important factor to consider during design and manufacturing of the pharmaceutical products. To-date, various strategies have been explored to tackle the issue of poor solubility. This review article focuses the updated overview of commonly used macro and nano drug delivery systems and techniques such as micronization, solid dispersion (SD), supercritical fluid (SCF), hydrotropy, co-solvency, micellar solubilization, cryogenic technique, inclusion complex formation-based techniques, nanosuspension, solid lipid nanoparticles, and nanogels/nanomatrices explored for solubility enhancement of poorly soluble drugs. Among various techniques, nanomatrices were found a promising and impeccable strategy for solubility enhancement of poorly soluble drugs. This article also describes the mechanism of action of each technique used in solubilization enhancement.

Solubilization of active ingredients of different polarity in Pluronic® micellar solutions - Correlations between solubilizate polarity and solubilization site.

The solubilization of two pharmaceutically active ingredients (AI) with significantly different water solubility, namely carbamazepine and fenofibrate (solubility of 150ppm and 10ppm, respectively), has been investigated using a series of Pluronics® (Poloxamers) containing different ethylene oxide and propylene oxide (EO/PO) units in the molecule. The results show largely enhanced solubilization of fenofibrate by Pluronic® micelles that increases with the PPO chain length provided the temperature is above the critical micelle temperature (cmt). In contrast the more water-soluble carbamazepine only shows a moderate increase in solubilization upon addition of Pluronics®. Small angle neutron scattering (SANS) and pulsed field gradient (PFG) NMR experiments show that the solubilization of fenofibrate occurs in the core of the micelles, whereas carbamazepine shows no direct association with the micelles. These clearly different solubilization mechanisms for the two AIs were confirmed by Nuclear Overhauser Enhancement Spectroscopy (NOESY) experiments, which show that fenofibrate interacts only with the PPO core of the micelle, whereas carbamazepine interacts with both PPO and PEO similarly. Accordingly, the large enhancement of the solubilization of fenofibrate is related to the fact that it is solubilized within the PPO core of the Pluronic® micelles, while the much more moderate increase of carbamazepine solubility is attributed to the change of solvent quality due to the presence of the amphiphilic copolymer and the interaction with the EO and PO units in solution.