Lower irritation microemulsion-based rotigotine gel: formulation optimization and in vitro and in vivo studies

Abstract

Background Rotigotine is a potent and selective D 1 , D 2 , and D 3 dopaminergic receptor agonist. Due to an extensive first-pass effect, it has a very low oral bioavailability (approximately 0.5% in rats). Purpose The present investigation aimed to develop a microemulsion-based hydrogel for transdermal rotigotine delivery with lower application site reactions. Methods Pseudoternary phase diagrams were constructed to determine the region of oil in water (o/w)-type microemulsion. Central composite design was used to support the pseudoternary phase diagrams and to select homogeneous and stable microemulsions with an optimal amount of rotigotine permeation within 24 hours. In vitro skin permeation experiments were performed, using Franz diffusion cells, to compare rotigotine-loaded microemulsions with rotigotine solutions in oil. The optimized formulation was used to prepare a microemulsion-based hydrogel, which was subjected to bioavailability and skin irritancy studies. Results The selected formulations of rotigotine-loaded microemulsions had enhanced flux and permeation coefficients compared with rotigotine in oil. The optimum microemulsion contained 68% water, 6.8% Labrafil ® , 13.44% Cremophor ® RH40, 6.72% Labrasol ® , and 5.04% Transcutol ® HP; the drug-loading rate was 2%. To form a microemulsion gel, 1% Carbomer 1342 was added to the microemulsion. The bioavailability of the rotigotine-loaded microemulsion gel was 105.76%±20.52% with respect to the marketed rotigotine patch (Neupro ® ). The microemulsion gel irritated the skin less than Neupro. Conclusion A rotigotine microemulsion-based hydrogel was successfully developed, and an optimal formulation for drug delivery was identified. This product could improve patient compliance and have broad marketability.

Approach for Development of Topical Ketoconazole-Loaded Microemulsions and Its Antifungal Activity

“…The in vitro permeation of optimized KME depicted that ketoconazole from KME permeated through the membrane by approximately 30 %, whereas it was retained in the membrane by approximately 60 % after 24 h. Our result was in accordance with a previous study that reported the combination of microemulsions with reduced water content revealed high drug deposition in the skin [35]. It is hypothesized that increasing Smix would reduce the skin hydration and permeation flux, and the small particle size of microemulsions would provide a large surface area for drug penetration [44,45]. Regarding the high skin retention, it is indicated that KME could effectively retain in the skin layer within the area of the target infection site and could have a longer antifungal action.…”

Critical appraisal of rotigotine transdermal system in management of Parkinson’s disease and restless legs syndrome – patient considerations

“…There is currently a lower irritation microemulsion-based RTG gel being studied and in the future, there may be formulations of RTG with less application site reactions. 58 Future comparator studies could better characterize the benefits of the RTG against other generic alternatives, and to better inform the clinician when choosing a therapy for PD or RLS.…”

Preparation and evaluation of microemulsion-based transdermal delivery of Cistanche tubulosa phenylethanoid glycosides

“…MEs may act as drug reservoirs, with the drug being released from the inner phase to the outer phase and then onto the skin. Furthermore, the MEs may affect the stratum corneum structure and reduce the diffusional barrier by acting as a permeation enhancer (26,33). …”