Phenolic compounds particle engineering and formulation with dense gas technology.

Abstract

Phenolic compounds have robust activity against free radicals, thus they possess potential in the treatment of various metabolic disorders such as cancer, diabetes, cardiovascular, osteoporosis and malaria. The application of the compounds, however, has been hindered by their intrinsic physicochemical properties of having poor solubility and stability in the human gastro-intestinal pathway. As a result, phenolic compounds have low oral bioavailability. Addressing the drawbacks such as those exhibited by phenolic compounds usually focuses on the strategy of processing and formulation. The processing can contribute to improvement of the physical properties of the compounds and exploration of alternative administration, while formulation can facilitate the modification of compound interactions with the targeted site of delivery. In this study, particle engineering and formulation were applied to phenolic compound of curcumin for development composite products. Derived compound of cyclodextrins; hydroxypropylated and methylated beta cyclodextrins, and water soluble polymer of polyvinylpyrrolidone (PVP) were used as excipients to investigate synergistic effect of the co-formulations. The method of dense gas anti-solvent technology was used throughout the study, using compressed CO2 as processing medium. Processing and formulation had succeeded to improve curcumin performance in term of dissolution property as 80% of curcumin in 200 min and enhancement of aqueous solubility of 190 times could be obtained. Inhalable powders of curcumin composite having enhanced properties on aerodynamic performance with 61% - compared to 11% of the unprocessed material - of fine particle fraction (FPF) was produced. In addition, inhalable powder exhibited improved aqueous solubility as high as 70 times. Further, the ARISE processed pulmonary products had enhanced activity towards lung cancer cells. Process scale-up to evaluate feasibility of the dense gas method of the atomized rapid injection solvent extraction (ARISE) system was also conducted both technically and economically. The applicability of the ARISE method to produce micrometric particle of phenolic para-coumaric acid was examined in the lab and pilot-lab scale processing. An evaluation on the economics has confirmed scalability of the ARISE method to process micro- or nanoscale materials at larger scale operation