Development of an UHPLC-MS/MS method to determine cutaneous biodistribution of cannabidiol after topical application of cannabidiol gel assisted by iontophoresis.

Cannabidiol has potential for use in skin disease therapy, so it is important to know the cutaneous biodistribution of cannabidiol after topical application of cannabidiol formulations. However, currently existing quantification methods for the investigation of cannabidiol skin distribution are not optimal. This study aimed to establish a method for the determination of cannabidiol in skin samples by UHPLC-MS/MS. A BEH C18 (50.0 × 2.1 mm, 2.5 µm) column was used; the mobile phase consisted of acetonitrile-0.1% formic acid (70:30, v/v), the flow rate was 0.2 µl·min-1 and the column temperature was 30°C. Positive-ion mode with multiple reaction monitoring detection was used to quantify cannabidiol (m/z 315.1 → 193.1) while diphenhydramine (m/z 256.3 → 167.08) served as the internal standard. Good linearity was shown in the range of 1-200 ng·ml-1 for cannabidiol with correlation coefficients of >0.999. The LLOQ was 1 ng·ml-1 . The intra-day and inter-day RSDs of cannabidiol were all <2%. A cryo-sectioning technique combined with the UHPLC-MS/MS method was used to successfully determine cannabidiol levels in a series of very thin skin layers.

Bolus delivery of palonosetron through skin by tip-loaded dissolving microneedles with short-duration iontophoresis: A potential strategy to rapidly relieve emesis associated with chemotherapy.

The objective of this study was to investigate the feasibility of the bolus administration of PLS via skin by using dissolving microneedles of palonosetron hydrochloride (PLS-DMNs). Tip-loaded PLS-DMNs were fabricated by a casting method using sodium hyaluronate (HA) as DMNs-forming polymer. PLS-DMNs were shown to have a content of 118.5 ± 8.7 µg per piece with sufficient mechanical strength for insertion into pig skin ex vivo. In situ dissolution of PLS-DMNs was achieved within 5 min and 83.2 % of PLS was delivered. In vitro studies showed that PLS-DMNs provided much higher PLS permeation than that after passive permeation using a PLS hydrogel. Moreover, the application of 30 min-iontophoresis at the beginning of PLS-DMNs administration further enhanced PLS delivery. In vivo pharmacokinetic studies were carried out in rats. The area under the curve (AUC) and the time to reach the peak (Tmax) after application of PLS-DMNs was not significantly different compared to those after subcutaneous (S.C.) injection. PLS-DMNs plus 30 min-iontophoresis enabled the pharmacokinetic profile to be even closer to that seen after S.C. administration. These results suggest that application of PLS-DMNs with short-duration iontophoresis exhibits promise as an alternative PLS delivery method that can be painlessly self-administered with rapid onset.