Tip loaded cyclodextrin-carvedilol complexes microarray patches
Carvedilol, a β-blocker prescribed for chronic heart failure, suffers from poor bioavailability and rapid first pass metabolism when administered orally. Herein, we present the development of tip microarray patches (MAPs) composed of ternary cyclodextrin (CD) complexes of carvedilol for transdermal delivery. The ternary complex with hydroxypropyl γ-cyclodextrin (HPγCD) and poly(vinyl pyrrolidone) (PVP) reduced the crystallinity of carvedilol, as evidenced by DSC, XRD, NMR, and SEM analysis. MAPs were fabricated using a two-step process with the ternary complex as the needle layer. The resulting MAPs were capable of breaching ex vivo neonatal porcine skin to a depth ≈600 μm with minimal impact to needle height. Upon insertion, the needle dissolved within 2 h, leading to the transdermal delivery of carvedilol. The MAPs displayed minimal toxicity and acceptable biocompatibility in cell assays. In rats, MAPs achieved significantly higher AUC levels of carvedilol than oral administration, with a delayed Tmax and sustained plasma levels over several days. These findings suggest that the carvedilol-loaded dissolving MAPs have the potential to revolutionise the treatment of chronic heart failure.
2.1. Materials
Carvedilol (C24H26N2O4) (MW 406.5 g/mol, purity >98 %) was purchased from Tokyo Chemical Industry (Oxford, UK). Cavasol™ W7 HP Pharma (hydroxypropyl-βCD) (C63H112O42) (MW 1410 g/mol), Cavasol™ W8 HP Pharma (hydroxypropyl-γCD) (C72H128O48) (MW 1540 g/mol), Plasdone™ K-29/32 or Poly(vinyl pyrrolidone) (PVP) (C6H9NO)n (MW 58,000 g/mol) and PVP K-90 (MW 1,300,000 g/mol) were kindly provided by Ashland (Kidderminster, UK). Poly(vinyl alcohol) (PVA) (C2H4O)n, 80 % hydrolysed (MW 9000–10,000 g/mol) was purchased from Sigma-Aldrich (Dorset, UK). Other chemicals and materials were of analytical grade and were bought from Sigma-Aldrich (Dorset, UK) and Fisher Scientific (Leicestershire, UK). Full-thickness and dermatomed neonatal porcine skin were collected from stillborn piglets in <24 h post-mortem. The skin was stored at −20 °C prior to use.
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Qonita Kurnia Anjani, Akmal Hidayat Bin Sabri, Khuriah Abdul Hamid, Natalia Moreno-Castellanos, Huanhuan Li, Ryan F. Donnelly, Tip loaded cyclodextrin-carvedilol complexes microarray patches, Carbohydrate Polymers, Volume 320, 2023, 121194, ISSN 0144-8617,
https://doi.org/10.1016/j.carbpol.2023.121194.