Diclofenac (CAS 15307-86-5) is a non-steroidal anti-inflammatory drug largely used, mainly to relief pain of various origin. Diclofenac is present on the market as free acid, as sodium salt (CAS 15307-79-6) and as potassium salt (CAS 15307-81-0). The last salification form has shown a prompter absorption rate and a faster onset of analgesic activity than the acid form and sodium salt. This paper extensively reviews three trials carried out on healthy volunteers, where potassium salt of diclofenac present in three fast-acting formulations, namely sachets (Trial 1), tablets (Trial 2) and oral drops (Trial 3), were compared to reference tablet formulations from the market. A very fast absorption rate was encountered with the three test formulations, with the peak reached in one case 5 min and in most cases within 10-15 min after dosing. The quick absorption rate of test formulations was attributed to the special combination of the salt of diclofenac with a dynamic buffering agent, namely bicarbonate, present in the test formulations and covered by an international patent. The prompt absorption of diclofenac from the new fast-acting formulations was accompanied by the presence of only one peak, whereas the reference formulations produced in most cases two peaks, as widely described in literature. This finding suggested the hypothesis that the absorption of test formulations should occur in a shorter tract of the gut. The faster absorption of diclofenac from the three fast-acting formulations is expected to produce a faster onset of analgesic action, which highlights these new formulations as particularly indicated to relief pain of any origin.

Introduction To eliminate the COVID-19 pandemic, the transmission of the virus SARS-CoV-2 among the population needs to be blocked and/or at least reduced. Upper respiratory tract viral loads are highest in the early stages of the disease, and high loads are associated with higher mortality rates. This study aims to evaluate the virucidal efficacy of AOS2020, a novel sprayable Acid-Oxidizing solution containing pure and stable hypochlorous acid (HClO), on human coronavirus SARS-Cov-2 in vitro, and the tolerability profile on nasal and oral mucosa suggesting to be a potential solution for upper respiratory hygiene. Method Virucidal assays and intranasal and oral irritation tests were undertaken in accordance with relevant national and international guidance and methods. Results In pre-clinical tests, the AOS2020, showed > 99.8% virucidal efficacy in < 1 min against SARS-Cov-2. The safety profile testing on both the nasal and oral mucosa indicates that AOS2020 is non-irritant. Conclusion These initial results indicate that this product has the potential treatment to reduce viral load in the upper respiratory tract.

An innovative technology (Physiomimic Technology) has been applied to amino acids (AAs) formulated for patients with phenylketonuria, with the objective of masking AA taste and odor and prolonging AA release in the gut, allowing a physiological absorption. This technology entails that the AAs are processed with functional additives that are able to modify their release and their organoleptic features. Two prototypes, obtained using sodium alginate þ ethylcellulose (engP-1) or sodium alginate þ ethylcellulose þ glyceryl dibehenate (engP-2), have been tested for AA prolonged release versus the same AAs (n-engP) without the application of the Physiomimic Technology. In vitro tests indicated that the technology is able to prolong the release of the engineered AAs versus the free compounds. A crossover in vivo kinetic study in pigs showed reduced peak concentrations (C max ) and, as expected, similar areas under the concentration/time curve (up to 5 hours) for the engineered products versus the free AAs. Significantly lower C max values (P < .01) were attained for essential AAs, large neutral AAs, and branched-chain AAs, indicating that the technology is able to reduce the typical absorption peak of free AAs. Taste and odor masking has been obtained as a consequence of the AA coating. The Physiomimic Technology, applied to free AAs, provided AA mixes with improved organoleptic features and with modified AA kinetics sustaining a more physiological AA absorption.

Several disorders of amino acid (AA) metabolism are treated with a protein-restricted diet supplemented with specific AA mixtures. Delivery kinetics impacts AA absorption and plasma concentration profiles. We assessed plasma profiles after ingestion of an AA mixture engineered to prolong AA absorption with Physiomimic TechnologyTM (Test) in a randomized, single-dose, four-way crossover trial in healthy volunteers (Trial Registration: ISRCTN11016729). In a two-step hypothesis, the primary endpoints were (i) significant reduction in peak plasma concentrations (Cmax) of essential amino acids (EAAs) while (ii) maintaining EAA bioavailability (AUC0-300 min) compared to a free AA mixture (Reference). Secondary endpoints included effects on plasma profiles of other AA groups and effects on several metabolic markers. Thirty subjects completed the study. Both co-primary endpoints were met: Cmax for EAAs was 27% lower with the Test product compared to the Reference product (ratio, 0.726, p < 0.0001); overall plasma EAA levels from the two AA mixtures was within the pre-specified bioequivalence range (AUC0-300min ratio, 0.890 (95% CI: 0.865, 0.915)). These findings were supported by the results of secondary endpoints. Prolongation of AA absorption was associated with modulation of several metabolic markers. It will be important to understand whether this can improve the long-term management of disorders of AA metabolism.

The diffusion into the target tissues of ketoprofen (CAS 22071-15-4), a widely used nonsteroidal anti-inflammatory drug, from a new topical patch has been studied after repeated patch application in comparison with its plasma level. Ten patients (5 women and 5 men) with a mean age of 45.0 +/- 12.3 years (mean +/- SD), scheduled for arthroscopic meniscectomy (5 subjects) or endoscopic carpal tunnel decompression (5 subjects), were asked to apply one patch with 100 mg ketoprofen on the affected body site once a day during the 6 days before the scheduled surgery. The last patch was kept for 6 h, and removed just a few minutes before surgery, when venous blood was drawn. Biopsies of the synovial tissue of the medial compartment and of the anterior fat pad (Hoffa's tissue) or of the ulnar bursa were taken during knee arthroscopy or endoscopic carpal tunnel release, respectively. An average plasma value of 52.8 +/- 30.1 (SD) ng/ml of ketoprofen was obtained in the 10 patients. The tissue concentrations of ketoprofen in the 5 subjects undergoing knee arthroscopy were 27.9 +/- 26.1 ng/g (range 7.2-67.1 ng/g) in the anterior fat pad and 239.0 +/- 163.0 ng/g (range 20.0-430.5 ng/g) in the synovial tissue. Drug concentrations up to 1000 times higher were found in the tendon sheath tissue of the ulnar bursa of the five patients undergoing endoscopic carpal tunnel release: average values of 20,107 +/- 7359 ng/g (range 13,004-32,578 ng/g) were obtained in this tissue. Data observed in this trial are consistent with those previously published by other authors, and demonstrate that ketoprofen applied on the skin is able to enter the subcutaneous and intra-articular tissues, reaching concentrations markedly higher than in plasma, and is further able to produce the desired pharmacological activity in situ, whereas plasma concentrations are too low to produce any systemic activity or side effect.