Lovastatin (LVS) is an effective therapeutic and prophylactic agent in several cardiovascular disorders. However, it has low bioavailability. This study investigated solute-solvent and solute-cosolute interactions and assessed thermodynamic parameters that contributed to LVS solubility enhancement in the presence of arginine (ARG) as a hydrotropic agent. The electrolytic conductance of LVS-ARG binary system was measured at temperatures from 298.15 K to 313.15 K. Conductometric parameters such as limiting molar conductance was evaluated. Additionally, thermodynamic parameters (ΔG0, ΔH0, ΔS0 and ES) involved in the association process of the solute in the aqueous solution of ARG solution were determined systematically. Solubility markedly improved 43-fold in the LVS-ARG complex compared to LVS alone. The analysed data from values of molar conductance and activation energy suggested favourable solubilisation, with a stronger solute-solvent interaction between LVS-ARG in water at higher temperatures. ARG and LVS complexation caused by strong molecular interactions was confirmed by spectral results. Hence, the addition of ARG as a co-solute was proven to enhance LVS solubility in water. The obtained data will ultimately enable the development of desired highly soluble, more efficient and safer LVS preparations.
Bone fracture, being mainly caused by mechanical stress, requires special and quick attention for a rapid healing. The study presented here aims at formulating nanoparticulate system to overcome the solubility issues of lovastatin. The lovastatin nanoparticles were successfully prepared by ionotropic gelation method using chitosan and tri-polyphosphate as polymers. Thus prepared nanoparticles were found to be smooth and spherical with average particle size of 87 nm and encapsulation efficiency of 86.5%. The in-vitro drug release was found to be almost 89.6% in the first 360 minutes. Artificial fracture was produced in female Wistar rats at right leg using fracture apparatus. After administration of lovastatin nanoparticles or saline solution, the respective groups were observed for various parameters. The X-ray imaging showed that lovastatin accelerated bone healing, compared to control. The growth of animals was not hampered by lovastatin by any means. The radiographic examination confirmed a role of lovastatin in increasing bone density. The histological study showed the broken, proliferated and discontinued trabecullae in the control, while at the same time point, the normal, thick, continuous and connected trabecullae were observed in animals administered with lovastatin nanoparticles. The biomechanical studies showed high breaking resilience and minimum bone brittleness in animals injected with lovastatin nanoparticles. Considering these observations we state that lovastatin helps in rapid bone healing after fracture via increasing the bone density.
Ability of two strains of Aspergillus terreus (ATCC 74135 and ATCC 20542) for production of lovastatin in solid state fermentation (SSF) using rice straw (RS) and oil palm frond (OPF) was investigated. Results showed that RS is a better substrate for production of lovastatin in SSF. Maximum production of lovastatin has been obtained using A. terreus ATCC 74135 and RS as substrate without additional nitrogen source (157.07 mg/kg dry matter (DM)). Although additional nitrogen source has no benefit effect on enhancing the lovastatin production using RS substrate, it improved the lovastatin production using OPF with maximum production of 70.17 and 63.76 mg/kg DM for A. terreus ATCC 20542 and A. terreus ATCC 74135, respectively (soybean meal as nitrogen source). Incubation temperature, moisture content, and particle size had shown significant effect on lovastatin production (P < 0.01) and inoculums size and pH had no significant effect on lovastatin production (P > 0.05). Results also have shown that pH 6, 25°C incubation temperature, 1.4 to 2 mm particle size, 50% initial moisture content, and 8 days fermentation time are the best conditions for lovastatin production in SSF. Maximum production of lovastatin using optimized condition was 175.85 and 260.85 mg/kg DM for A. terreus ATCC 20542 and ATCC 74135, respectively, using RS as substrate.