Characterisation of Drug Delivery Efficacy Using Microstructure-Assisted Application of a Range of APIs

Abstract

Polymer-based solid microstructures (MSts) have the potential to significantly increase the quantity and range of drugs that can be administered across the skin. MSt arrays are used to demonstrate their capacity to bypass the skin barrier and enhance permeability by creating microchannels through the stratum corneum, in a minimally invasive manner. This study is designed to demonstrate the ability of MSts to exceed the current boundaries for transdermal delivery of compounds with different molecular weights, partition coefficients, acid dissociation constants, melting points, and water solubilities. In vitro permeation of a range of selected molecules, including acetyl salicylic acid (aspirin), galantamine, selegiline hydrochloride (Sel-HCl), insulin, caffeine, hydrocortisone (HC), hydrocortisone 21-hemisuccinate sodium salt (HC-HS) and bovine serum albumin (BSA) has been studied across excised porcine skin with and without poke and patch application of MSts. Permeation of the molecules was monitored using Franz diffusion cells over 24 h. MSts significantly increased the permeation of all selected molecules up to 40 times, compared to topical applications of the molecules without MSts. The greatest increase in permeation was observed for caffeine with 70 ± 8% permeation and the lowest enhancement was observed for HC with a 2.4 ± 1.3% increase in permeation. The highest obtained flux was BSA (8133 ± 1365 μg/cm2/h) and the lowest flux observed for HC (11 ± 4 μg/cm2/h). BSA and HC also showed the highest (16,275 ± 3078 μg) and the lowest (73 ± 47 μg) permeation amount after 24 h respectively. MSt-treated skin exhibits greatly increased permeation. The molecule parameters (size, acid dissociation constant, partition coefficient and solubility)—traditional hurdles associated with passive diffusion through intact skin—are overcome using MSt skin treatment.

Studies Regarding the Antimicrobial Behavior of Clotrimazole and Limonene

“…In addition, the value obtained for the partition coefficient in octanol (logP) is more favorable for clotrimazole (logP = 3.36) and the co-crystallized (log P = −4.72) ( Table 9 ). Analyzing the value of the partition coefficient (logP) in the two ligands ( Table 9 ), it can be appreciated that in the case of a mixture at low concentrations between the two compounds (i.e., clotrimazole; limonene), the presence of clotrimazole is determinant in transdermal delivery, due to the absence of the hydrogen bond [ 48 , 49 , 50 , 51 ], and more likely will be docked first.…”

The Impact of Water on Choline‐2‐Octenoic Ionic Liquid‐Facilitated Transdermal Transport

“…Choline 2‐octenoate 1:2 (CA2OE 1:2) was synthesized as previously reported. [ 6 ] Briefly, technical‐grade trans‐2‐octenoic acid [2OE] (85%, 142.20 g mol −1 , Sigma Aldrich O5209‐5G) was purified daily over the course of a week. This was accomplished by mixing the as‐received anion with high‐purity optima‐grade acetone (Fisher Chemical, #A929‐4) (1:1 v/v) and crystallizing the anion overnight at −80 °C in a sealed glass bottle.…”

“…This was likely due to the greater presence of water allowing for stronger intermolecular interactions. Dextran addition to the 10% v/v solution illus-trated the greatest spectral changes with the dextran diminishing the O─H interactions and compounding the signals of the C─H and C─O─C stretches with the addition of the substituted aromatic ring and 𝛼 (1)(2)(3)(4)(5)(6) glycosidic bond in the polysaccharide molecule.…”

“…[1,2] However, there are several challenges to overcome, namely, bypassing the formidable barrier posed primarily by the stratum corneum (SC), the external layer of the skin that consists of tightly packed lipids and differentiated corneocytes. [3,4] Only molecules within a small window of lipophilicity (log P of 3-5) and below 500 Da are capable of passing through the SC unassisted, [5,6] which leaves the vast majority of active ingredients requiring chemical or mechanical technologies to allow for transdermal penetration. These include physical methods such as sonication and microneedles, and chemical permeation enhancers.…”

Design and fabrication of r-hirudin loaded dissolving microneedle patch for minimally invasive and long-term treatment of thromboembolic disease

“…In 2016, the first 3D printed pharmaceutical product was approved by the United States Food and Drug Administration [32] . Currently, with the improvement of printing accuracy, high-precision micro 3D printing introduces a new era [33] , [34] , [35] , [36] , [37] , [38] . This enables the target micro mold to be easily obtained within hours through computer simulation and output for printing, largely simplifying the process of micro mold fabrication and saving time and cost.…”