6-o-palmitoylascorbic-acid and hesperetin

Systematic screening for optimal formulation composition and production parameters for nanosuspensions consumes a lot of time and also drug material when performed at lab scale. Therefore, a cost-effective miniaturized scale top down approach for nanocrystals production by wet bead milling was developed. The final set-up consisted of 3 magnetic stirring bars placed vertically one over the other in a 2 mL glass vial and agitated by a common magnetic stirring plate. All of the tested actives (cyclosporin A, resveratrol, hesperitin, ascorbyl palmitate, apigenin and hesperidin) could be converted to nanosuspensions. For 4 of them, the particles sizes achieved were smaller than previously reported on the literature (around 90 nm for cyclosporin A; 50 nm for hesperitin; 160 nm for ascorbyl palmitate and 80 nm for apigenin). The "transferability" of the data collect by the miniaturized method was evaluated comparing the production at larger scale using both wet bead milling and high pressure homogenization. Transferable information obtained from the miniaturized scale is minimum achievable size, improvements in size reduction by reduction of beads size, diminution kinetics and potentially occurring instabilities during processing. The small scale batches also allow identification of optimal stabilizer types and concentrations. The batch size is 0.5 mL, requiring approximately 50 mg or 5 mg of drug (5% and 1% suspension, respectively). Thus, a simple, accessible, low-cost miniaturized scale method for the production of pharmaceutical nanocrystals was established.

Topics: Apigenin; Ascorbic Acid; Chemistry, Pharmaceutical; Cyclosporine; Hesperidin; Miniaturization; Nanoparticles; Particle Size; Resveratrol; Stilbenes; Suspensions; Technology, Pharmaceutical

The antioxidant properties of freeze-dried citrus fruit peels (orange, lemon, grapefruit) and methanolic extracts from the peel were studied. Freeze-dried orange peel showed the highest, lemon peel somewhat less and grapefruit peel the lowest but still remarkable antioxidant activity. This could be significantly improved by preparing methanolic extracts of the peels. Comparative examinations and autoxidation studies with the flavanon glycosides hesperidin and naringin as well as with their aglycones hesperetin and naringenin showed that the former are mainly responsible for the antioxidative activity of the citrus peel and extracts. In order to compare their antioxidative activity with that of the commercially available natural antioxidants alpha-tocopherol and ascorbylpalmitate, the freeze-dried citrus peels and their methanolic extracts should be used in higher concentrations, in consideration of their peculiar properties and complex natural composition. Furthermore, aspects of the correlation between antioxidant activity and molecular structure of the flavanones were discussed.

Topics: Antioxidants; Ascorbic Acid; Citrus; Flavanones; Flavonoids; Freeze Drying; Hesperidin; Vitamin E