Investigation of binary and ternary solvent systems for dermal delivery of methadone

Kung, Chin-Ping; Zhang, Yanling; Sil, Bruno C.; Hadgraft, Jonathan; Lane, Majella E.; Patel, Bhumik; McCulloch, Renée

doi:10.1016/j.ijpharm.2020.119538

Cited by 15 publications

(8 citation statements)

References 41 publications

(49 reference statements)

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“…Additionally, several studies in the scientific literature have reported that combinations of solvents with differing physicochemical properties resulted in synergistic enhancement of drug permeation [ 58 , 59 , 60 , 61 , 62 , 63 ]. Brinkmann and Muller-Goymann (2003) investigated the effect of isopropanol (IPA) and a long-chain fatty acid ester, namely isopropyl myristate (IPM), on the permeation of hydrocortisone (HC) across isolated human SC [ 64 ].…”

Section: Resultsmentioning

confidence: 99%

Dermal Delivery of Diclofenac Sodium—In Vitro and In Vivo Studies

Iliopoulos¹,

Goh

Haque³

et al. 2022

Pharmaceutics

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Previously, we reported the use of confocal Raman spectroscopy (CRS) as a novel non-invasive approach to determine drug disposition in the skin in vivo. Results obtained by CRS were found to correlate with data from the well-established in vitro permeation test (IVPT) model using human epidermis. However, these studies used simple vehicles comprising single solvents and binary or ternary solvent mixtures; to date, the utility of CRS for monitoring dermal absorption following application of complex marketed formulations has not been examined. In the present work, skin delivery of diclofenac sodium (DFNa) from two topical dermatological drug products, namely Diclac® Lipogel 10 mg/g and Primofenac® Emulsion gel 1%, was determined by IVPT and in vivo by both CRS and tape stripping (TS) methodologies under similar experimental conditions. The in vivo data were evaluated against the in vitro findings, and a direct comparison between CRS and TS was performed. Results from all methodologies showed that Diclac promoted significantly greater DFNa delivery to the skin (p < 0.05). The cumulative amounts of DFNa which permeated at 24 h in vitro for Diclac (86.5 ± 9.4 µg/cm2) were 3.6-fold greater than the corresponding amounts found for Primofenac (24.4 ± 2.7 µg/cm2). Additionally, total skin uptake of DFNa in vivo, estimated by the area under the depth profiles curves (AUC), or the signal intensity of the drug detected in the upper stratum corneum (SC) (4 µm) ranged from 3.5 to 3.6-fold greater for Diclac than for Primofenac. The shape of the distribution profiles and the depth of DFNa penetration to the SC estimated by CRS and TS were similar for the two methods. However, TS data indicated a 4.7-fold greater efficacy of Diclac relative to Primofenac, with corresponding total amounts of drug penetrated, 94.1 ± 22.6 µg and 20.2 ± 7.0 µg. The findings demonstrate that CRS is a methodology that is capable of distinguishing skin delivery of DFNa from different formulations. The results support the use of this approach for non-invasive evaluation of topical products in vivo. Future studies will examine additional formulations with more complex compositions and will use a wider range of drugs with different physicochemical properties. The non-invasive nature of CRS coupled with the ability to monitor drug permeation in real time offer significant advantages for testing and development of topical dermatological products.

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Section: Resultsmentioning

confidence: 99%

Dermal Delivery of Diclofenac Sodium—In Vitro and In Vivo Studies

Iliopoulos¹,

Goh

Haque³

et al. 2022

Pharmaceutics

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“…Based on these results, a combination of MCT and DEGEE at different ratios were prepared, each of their solubility capacities was evaluated using the same method. It has been reported before that the combination of binary solvents could promote skin permeation though a mechanism that is not well known yet [ 38 ]. Therefore, the combination of DEGEE and MCT was selected to be used for the formulation of the nanoemulsion.…”

Section: Resultsmentioning

confidence: 99%

Anti-Melanogenic Mechanism of Tetrahydrocurcumin and Enhancing Its Topical Delivery Efficacy Using a Lecithin-Based Nanoemulsion

Tang

Dong

et al. 2021

Pharmaceutics

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Tetrahydrocurcumin (THC) has been well known for its superior antioxidant properties. Therefore, it is speculated that it might be effective to relieve oxidative stress-induced diseases, such as skin hyperpigmentation. In this work, an in vitro B16F10 melanoma cell model was used to study the impact of THC on the melanogenic process under stressed conditions. It was demonstrated that THC could effectively inhibit the α-MSH (melanocyte-stimulating hormone) induced melanin production in B16F10 melanoma cells and the expressions of three key enzymes involved with the biosynthetic process of melanin, tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2), were all significantly reduced. In addition, an in vitro human keratinocyte cell model was used to investigate the potential protective role of THC on H2O2-induced cytotoxicity. It was found that THC could prevent H2O2-induced oxidative stress based on the results of both the cell viability study and the intracellular ROS (reactive oxygen species) study assessed by the flow cytometry. Last, THC was formulated into a lecithin based nanoemulsion, and an in vitro Franz diffusion cell study using Strat-M® membrane concluded that the nanoemulsion could significantly enhance the membrane permeation compared to the unformatted THC suspension. This research demonstrated the anti-melanogenic benefits of THC on the melanoma and keratinocyte cell models and the topical delivery efficacy could be significantly enhanced using a lecithin based nanoemulsion.

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“…The mechanisms of action for PG and fatty acids were systematically reviewed by Lane [ 35 ]. PG is a solvent that is widely used in topical formulations, and the uptake of PG in human skin has been reported previously [ 36 , 37 , 38 ]. The solubility of NIA in PG has been previously reported as 28% ( w/v ) at 32 °C [ 25 ].…”

Section: Resultsmentioning

confidence: 99%

Dermal Delivery of Niacinamide—In Vivo Studies

et al. 2021

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In vivo human studies are considered to be the “gold standard” when investigating (trans)dermal delivery of actives. Previously, we reported the effects of a range of vehicles on the delivery of niacinamide (NIA) using conventional Franz cell studies. In the present work, dermal delivery of NIA was investigated in vivo in human subjects using confocal Raman spectroscopy (CRS) and tape stripping (TS). The vehicles investigated included propylene glycol (PG), Transcutol® P (TC), binary combinations of PG with oleic acid (OA) or linolenic acid (LA) and a ternary system comprising of TC, caprylic/capric triglyceride (CCT) and dimethyl isosorbide (DMI). For the CRS studies, higher area under curve (AUC) values for NIA were observed for the PG:LA binary system compared with PG, TC and TC:CCT:DMI (p < 0.05). A very good correlation was found between the in vitro cumulative permeation of NIA and the AUC values from Raman intensity depth profiles, with a Pearson correlation coefficient (R2) of 0.84. In addition, an excellent correlation (R2 = 0.97) was evident for the signal of the solvent PG and the active. CRS was also shown to discriminate between NIA in solution versus crystalline NIA. The findings confirm that CRS is emerging as a powerful approach for dermatopharmacokinetic studies of both actives and excipients in human.

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Investigation of binary and ternary solvent systems for dermal delivery of methadone

Cited by 15 publications

References 41 publications

Dermal Delivery of Diclofenac Sodium—In Vitro and In Vivo Studies

Dermal Delivery of Diclofenac Sodium—In Vitro and In Vivo Studies

Anti-Melanogenic Mechanism of Tetrahydrocurcumin and Enhancing Its Topical Delivery Efficacy Using a Lecithin-Based Nanoemulsion

Dermal Delivery of Niacinamide—In Vivo Studies

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