Biocatalytic Approach for Direct Esterification of Ibuprofen with Sorbitol in Biphasic Media.

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) introduced in the 1960s and widely used as an analgesic, anti-inflammatory, and antipyretic. In its acid form, the solubility of 21 mg/L greatly limits its bioavailability. Since the bioavailability of a drug product plays a critical role in the design of oral administration dosage, this study investigated the enzymatic esterification of ibuprofen as a strategy for hydrophilization. This work proposes an enzymatic strategy for the covalent attack of highly hydrophilic molecules using acidic functions of commercially available bioactive compounds. The poorly water-soluble drug ibuprofen was esterified in a hexane/water biphasic system by direct esterification with sorbitol using the cheap biocatalyst porcine pancreas lipase (PPL), which demonstrated itself to be a suitable enzyme for the effective production of the IBU-sorbitol ester. This work reports the optimization of the esterification reaction.

Biotransformation of Cortisone with Rhodococcus rhodnii: Synthesis of New Steroids.

Cortisone is a steroid widely used as an anti-inflammatory drug able to suppress the immune system, thus reducing inflammation and attendant pain and swelling at the site of an injury. Due to its numerous side effects, especially in prolonged and high-dose therapies, the development of the pharmaceutical industry is currently aimed at finding new compounds with similar activities but with minor or no side effects. Biotransformations are an important methodology towards more sustainable industrial processes, according to the principles of "green chemistry". In this work, the biotransformation of cortisone with Rhodococcus rhodnii DSM 43960 to give two new steroids, i.e., 1,9ß,17,21-tetrahydoxy-4-methyl-19-nor-9ß-pregna-1,3,5(10)-trien-11,20-dione and 1,9ß,17,20ß,21-pentahydoxy-4-methyl-19-nor-9ß-pregna-1,3,5(10)-trien-11-one, is reported. These new steroids have been fully characterized.

Glyceric Prodrug of Ursodeoxycholic Acid (UDCA): Novozym 435-Catalyzed Synthesis of UDCA-Monoglyceride.

Bile acids (BAs) are a family of steroids synthesized from cholesterol in the liver. Among bile acids, ursodeoxycholic acid (UDCA) is the drug of choice for treating primary biliary cirrhosis and dissolving cholesterol gallstones. The clinical effectiveness of UDCA includes its choleretic activity, the capability to inhibit hydrophobic bile acid absorption by the intestine under cholestatic conditions, reducing cholangiocyte injury, stimulation of impaired biliary output, and inhibition of hepatocyte apoptosis. Despite its clinical effectiveness, UDCA is poorly soluble in the gastro-duodeno-jejunal contents, and pharmacological doses of UDCA are not readily soluble in the stomach and intestine, resulting in incomplete absorption. Indeed, the solubility of 20 mg/L greatly limits the bioavailability of UDCA. Since the bioavailability of drug products plays a critical role in the design of oral administration dosages, we investigated the enzymatic esterification of UDCA as a strategy of hydrophilization. Therefore, we decided to enzymatically synthesize a glyceric ester of UDCA bile acid to produce a more water-soluble molecule. The esterification reactions between UDCA and glycerol were performed with an immobilized lipase B from Candida antarctica (Novozym 435) in solvent-free and solvent-assisted systems. The characterization of the UDCA-monoglyceride, enzymatically synthesized, has been performed by 1H-NMR, 13C-NMR, COSY, HSQC, HMBC, IR, and MS spectroscopy.

Δ1-Dehydrogenation and C20 Reduction of Cortisone and Hydrocortisone Catalyzed by Rhodococcus Strains.

Prednisone and prednisolone are steroids widely used as anti-inflammatory drugs. Development of the pharmaceutical industry is currently aimed at introducing biotechnological processes and replacing multiple-stage chemical syntheses. In this work we evaluated the ability of bacteria belonging to the Rhodococcus genus to biotransform substrates, such as cortisone and hydrocortisone, to obtain prednisone and prednisolone, respectively. These products are of great interest from a pharmaceutical point of view as they have higher anti-inflammatory activity than the starting substrates. After an initial lab-scale screening of 13 Rhodococcus strains, to select the highest producers of prednisone and prednisolone, we reported the 200 ml-batch scale-up to test the process efficiency and productivity of the most promising Rhodococcus strains. R. ruber, R. globerulus and R. coprophilus gave the Δ1-dehydrogenation products of cortisone and hydrocortisone (prednisone and prednisolone) in variable amounts. In these biotransformations, the formation of products with the reduced carbonyl group in position C20 of the lateral chain of the steroid nucleus was also observed (i.e., 20ß-hydroxy-prednisone and 20ß-hydroxy-prednisolone). The yields, the absence of collateral products, and in some cases the absence of starting products allow us to say that cortisone and hydrocortisone are partly degraded.

Electrolyzed Hypochlorous Acid (HOCl) Aqueous Solution as Low-Impact and Eco-Friendly Agent for Floor Cleaning and Sanitation.

Recently, the use of disinfectants has been becoming a diffused and sometimes indiscriminate practice of paramount importance to limit the spreading of infections. The control of microbial contamination has now been concentrated on the use of traditional agents (i.e., hypochlorite, ozone). However, their prolonged use can cause potential treats, for both human health and environment. Currently, low-impact but effective biocides that are prepared in a way that avoids waste, with a very low toxicity, and safe and easy to handle and store are strongly needed. In this study, produced electrochemically activated hypochlorous (HOCl) acid solutions are investigated and proposed, integrated in a scrubbing machine for floor cleaning treatment. Such an innovative machine has been used for floor cleaning and sanitation in order to evaluate the microbial charge and organic dirt removal capacity of HOCl in comparison with a machine charged with traditional Ecolabel standard detergent. The potential damage on floor materials has also been investigated by means of Scanning Electron Microscope (SEM). A comparative Life Cycle Assessment (LCA) analysis has been carried out for evaluating the sustainability of the use of the HOCl-based and detergent-based machine.