M.M.R. Meor Mohd Affandi

Solubility enhancement of simvastatin by arginine: thermodynamics, solute–solvent interactions, and spectral analysis

We examined the solubility of simvastatin in water in 0.01 mol·dm−3, 0.02 mol·dm−3, 0.04 mol·dm−3, 0.09 mol·dm−3, 0.18 mol·dm−3, 0.36 mol·dm−3, and 0.73 mol·dm−3 arginine (ARG) solutions. The investigated drug is termed the solute, whereas ARG the cosolute. Phase solubility studies illustrated a higher extent of solubility enhancement for simvastatin. The aforementioned system was subjected to conductometric and volumetric measurements at temperatures (T) of 298.15 K, 303.15 K, 308.15 K, and 313.15 K to illustrate the thermodynamics involved and related solute–solvent interactions. The conductance values were used to evaluate the limiting molar conductance and association constants. Thermodynamic parameters (ΔG0, ΔH0, ΔS0, and Es) for the association process of the solute in the aqueous solutions of ARG were calculated. Limiting partial molar volumes and expansibilities were evaluated from the density values. These values are discussed in terms of the solute–solvent and solute–cosolute interactions. Further, these systems were analyzed using ultraviolet–visible analysis, Fourier-transform infrared spectroscopy, and 13C, 1H, and two-dimensional nuclear overhauser effect spectroscopy nuclear magnetic resonance to complement thermophysical explanation.

Conductometric and volumetric studies of atorvastatin in aqueous solution of arginine from 298.15 to 313.15 K.

Categorized as a Biopharmaceutics Classification System Class II drugs, atorvastatin (ATV) exhibits low aqueous solubility and bioavailability thus presenting an obstacle and great challenge to formulation researchers. Numerous studies are available in regard to the solubility enhancement of ATV, but very few actually describe this phenomenon in terms of thermodynamics and the solute-solvent interaction. Arginine (ARG) is an amino acid that has been reported to enhance the solubility of the highly insoluble wheat protein gluten through hydrogen bonding and π electron-cation interaction. To our knowledge, ARG has never been investigated as a solubility enhancement agent of aqueous insoluble drugs. Thus, this study aimed to elucidate the solute-solvent and solute-cosolute interactions and derive thermodynamic parameters that bolstered the solubility of ATV in the presence of ARG. We examined the electrolytic conductance and densities of ATV-ARG binary system covering the temperature ranging from 298.15 K to 313.15 K. Conductometric and volumetric parameters such as limiting molar conductance, association constants, limiting partial molar volumes, and expansibility values were calculated. Additionally, thermodynamic parameters (ΔG0, ΔH0, ΔS0, and Es) involved in the association process of the solute in the aqueous solution of ARG were also determined.

Tissue Distribution of Astaxanthin Formulation in Rats

Background: Nano size emulsion of Astaxanthin has been successfully developed. However, its bioavailability enhancement benefit in form of concentration absorbed and tissue distribution has not been studied yet. Objective: This study investigated the relationship between globule size and tissue distribution of different types of astaxanthin formulation namely macro, nano and oil solution. Method: Twenty male rats were divided into four groups and orally fed with the formulations for seven days. The first, second, and third group of rats were fed with nano emulsion, macro emulsion and oil solution, respectively. The final group was used as negative control. The lungs, spleen, kidney, heart and liver were isolated for distribution study. Results: It was found that the nano size emulsion of astaxanthin contained the highest distribution in all organs while the highest concentration of astaxanthin was found in the spleen for each type of formulation. Conclusion: it is concluded that nano sized emulsion improved distribution and enhance the bioavailability of astaxanthin.