Controlled release of amitriptyline via the transdermal route using SmartReservoirs and hydrogel-forming microneedles

Abstract

SmartReservoirs (SRs) are novel drug reservoirs made from a cellulose-based matrix for hydrogel-forming microneedles (HF-MNs). SRs can incorporate drug molecules within a cellulose-based matrix in amorphous form. This significantly improves the solubility of poorly soluble drugs, which enhances drug delivery by allowing for rapid dissolution and absorption once the dosage form is administered. In contrast to improving the solubility of hydrophobic drugs, SRs might be used to modify the amorphous/crystalline properties of hydrophilic drugs, thus leading to a controlled release profile. Hence, SRs hold a promise as drug reservoirs for hydrophilic drugs and has not yet been investigated for such drugs; this study explores the transdermal delivery of the hydrophilic model drug amitriptyline hydrochloride (AMT) using SRs.

Highlights

• SmartReservoirs (SRs) are suitable for delivering hydrophilic drugs
• The type of cellulose matrix used in SRs can significantly influence the drug loading capacity
• The cellulose matrix also plays a critical role in modulating the transdermal release profile
• SRs enable controlled transdermal delivery of hydrophilic drugs

Furthermore, the effect of the cellulose-based matrix on drug loading and release profile was also tested using tissue paper-based (SR-T) and copier paper-based (SR-P) SmartReservoirs. The current research involves the fabrication of HF-MNs and two types of AMT-SRs. Subsequently, a comprehensive characterisation of the HF-MNs and SRs was conducted regarding their morphological features, mechanical and physicochemical properties, amorphous/crystallinity state, interaction with the cellulose matrix, drug distribution, drug loading capacity, and transdermal permeation efficiency. The findings of the study demonstrated that the active pharmaceutical ingredient (API) remained intact within the cellulose matrices of both SRs. The type of cellulose matrix employed had a major influence on the loading and release of the drug.

The SR-P demonstrated a significantly enhanced drug loading and release profile compared to the SR-T. The drug content analysis of the SRs revealed that SR-T had approximately 4 mg/cm² of AMT, in comparison to SR-P, which had a concentration nearly double that amount. The results of the skin deposition and permeation studies were also consistent, indicating that SR-T combined with HF-MNs deposited approximately 75 μg and permeated <150 μg (~5 % delivered), while SR-P combined with HF-MNs deposited approximately 128 μg and permeated >500 μg of AMT into the skin (~9 % delivered). Ultimately, this work provides substantial evidence to support the use of SRs as a hydrophilic drug reservoir for HF-MNs.

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Materials

AMT (hydrochloride salt; purity >98 %) was procured from Tokyo Chemical Industry (Oxford, UK). Ethanol absolute was obtained from VWR Chemicals (Leicestershire, UK). Methanol for HPLC (purity ≥99.9 %), poly (vinyl alcohol) with an average molecular weight 85–124 kDa (87–89 % hydrolysed), and citric acid monohydrate (purity ≥99 %) were all purchased from Sigma-Aldrich (Dorset, UK). Poly (vinyl pyrrolidone) sold under the brand name of Plasdone™ K-29/32 with a molecular weight of 58 kDa was supplied by Ashland Industries Europe GmbH (Schaffhausen, Switzerland). Ultrapure water, classified as HPLC grade, was obtained from a water purification system named as Elga PURELAB DV 25, Veolia Water Systems (Dublin, Ireland).

Abraham M. Abraham, Amitha Simon, Qonita Kurnia Anjani, Yueming Jiang, Masoud Adhami, Juan Domínguez-Robles, Eneko Larrañeta, Ryan F. Donnelly, Controlled release of amitriptyline via the transdermal route using SmartReservoirs and hydrogel-forming microneedles, Biomaterials Advances, Volume 176, 2025, 214361, ISSN 2772-9508, https://doi.org/10.1016/j.bioadv.2025.214361.

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