Development and application of a chromatographic method for simultaneous quantification of 5-fluorouracil and imiquimod in drug-in-adhesive topical patches

Kim, Sangseo; Youssef, Souha H.; Song, Yunmei; Garg, Sanjay

doi:10.1016/j.scp.2022.100711

Cited by 3 publications

(3 citation statements)

References 32 publications

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“… 24 Similarly, green analytical chemistry (GAC) was introduced in the early 2000s and 12 principles of GAC were defined. 25 Several metrics were developed, namely, national environmental methods index (NEMI), 26 Raynie and Driver’s assessment tool, 27 eco-scale assessment (ESA), 28 green analytical procedure index (GAPI), 29 and Analytical GREEnness Metric Approach and Software (AGREE). 30 However, unlike GC and GAC, the assessment of the environmental impact of formulation processes is not extensively discussed in the literature.…”

Section: Introductionmentioning

confidence: 99%

Development and Optimization of Imiquimod-Loaded Nanostructured Lipid Carriers Using a Hybrid Design of Experiments Approach

Kim¹,

Abdella²,

Abid³

et al. 2023

IJN

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Background Imiquimod (IMQ) is an immunomodulating drug that is approved for the treatment of superficial basal cell carcinoma, actinic keratosis, external genital warts and perianal warts. However, IMQ cream (Aldara ® ) has several drawbacks including poor skin permeation, local toxicity, and compromised patient compliance as a topical pharmacological option. Methods Our research aimed to develop and optimize nanostructured lipid carriers (NLCs) containing IMQ for the first time using a hybrid design of experiments approach. The optimized formulation was then incorporated into a matrix-type topical patch as an alternative dosage form for topical application and evaluated for IMQ deposition across different skin layers in comparison to the performance of the commercial product. Additionally, our work also attempted to highlight the possibility of implementing environment-friendly practices in our IMQ-NLCs formulation development by reviewing our analytical methods and experimental designs and reducing energy and solvent consumption where possible. Results In this study, stearyl alcohol, oleic acid, Tween ® 80 (polysorbate 80), and Gelucire ® 50/13 (Stearoyl polyoxyl-32 glycerides) were selected for formulation development. The formulation was optimized using a 2 k factorial design and a central composite design. The optimized formulation achieved the average particle size, polydispersity index, and zeta potential of 75.6 nm, 0.235, and – 30.9 mV, respectively. Subsequently, a matrix-type patch containing IMQ-NLCs was developed and achieved a statistically significant improvement in IMQ deposition in the deeper skin layers. The IMQ deposition from the patch into the dermis layer and receptor chamber was 3.3 ± 0.9 µg/cm 2 and 12.3 ± 2.2 µg/cm 2 , while the commercial cream only deposited 1.0 ± 0.8 µg/cm 2 and 1.5 ± 0.5 µg/cm 2 of IMQ, respectively. Conclusion In summary, IMQ-NLC-loaded patches represent great potential as a topical treatment option for skin cancer with improved patient compliance.

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Section: Introductionmentioning

confidence: 99%

Development and Optimization of Imiquimod-Loaded Nanostructured Lipid Carriers Using a Hybrid Design of Experiments Approach

Kim¹,

Abdella²,

Abid³

et al. 2023

IJN

Self Cite

View full text Add to dashboard Cite

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“…It may be due to the inclusion of chemical permeation enhancers in the formulation as a less or non-volatile compound, which resulted in slightly thicker films after drying compared to the Patch-CONT. The surface pH of the patches ranged from 6.06 ± 0.03 to 6.33 ± 0.07 for Patch-CONT and Patch-OA, which were all found to be within the normal range of the skin, indicating that potential local irritation caused by the patches to the skin would be minimal [ 27 ]. Moreover, the % moisture content and % moisture absorption of the patches were also found to be minimal, ranging from 1.60 ± 0.35% to 2.33 ± 0.82% and 2.67 ± 0.85% to 3.91 ± 1.53%, respectively.…”

Section: Resultsmentioning

confidence: 99%

Enhanced Skin Permeation of 5-Fluorouracil through Drug-in-Adhesive Topical Patches

Kim,

Youssef,

Lee

et al. 2024

Pharmaceutics

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5-fluorouracil (5-FU), commercially available as a topical product, is approved for non-melanoma skin cancer (NMSC) treatment with several clinical limitations. This work aimed to develop 5-FU-loaded topical patches as a potential alternative to overcome such drawbacks. The patches offer accurate dosing, controlled drug release and improved patient compliance. Our study highlights the development of Eudragit® E (EuE)-based drug-in-adhesive (DIA) patches containing a clinically significant high level of 5-FU (approximately 450 µg/cm2) formulated with various chemical permeation enhancers. The patches containing Transcutol® (Patch-TRAN) or oleic acid (Patch-OA) demonstrated significantly higher skin penetration ex vivo than their control counterpart, reaching 5-FU concentrations of 76.39 ± 27.7 µg/cm2 and 82.56 ± 8.2 µg/cm2, respectively. Furthermore, the findings from in vitro permeation studies also validated the superior skin permeation of 5-FU achieved by Patch-OA and Patch-TRAN over 72 h. Moreover, the EuE-based DIA patch platform demonstrated suitable adhesive and mechanical properties with an excellent safety profile evaluated through an inaugural in vivo human study involving 11 healthy volunteers. In conclusion, the DIA patches could be a novel alternative option for NMSC as the patches effectively deliver 5-FU into the dermis layer and receptor compartment ex vivo for an extended period with excellent mechanical and safety profiles.

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“…Continuing this success, another DIA patch using Eudragit ® E and triacetin was also developed by our group. In this patch, a combination of both 5-FU and IMQ was evaluated for their potential use in NMSC (Figure 5) [69]. The patches were formulated to contain 81.4 ± 0.57 µg/0.64 cm 2 of 5-FU and 82.5 ± 0.50 µg/0.64 cm 2 of IMQ.…”

Section: Polymeric Drug-in-adhesive and Matrix-type Patchesmentioning

confidence: 99%

Innovative Topical Patches for Non-Melanoma Skin Cancer: Current Challenges and Key Formulation Considerations

Kim,

Day,

Song

et al. 2023

Pharmaceutics

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Non-melanoma skin cancer (NMSC) is the most prevalent malignancy worldwide, with approximately 6.3 million new cases worldwide in 2019. One of the key management strategies for NMSC is a topical treatment usually utilised for localised and early-stage disease owing to its non-invasive nature. However, the efficacy of topical agents is often hindered by poor drug penetration and patient adherence. Therefore, various research groups have employed advanced drug delivery systems, including topical patches to overcome the problem of conventional topical treatments. This review begins with an overview of NMSC as well as the current landscape of topical treatments for NMSC, specifically focusing on the emerging technology of topical patches. A detailed discussion of their potential to overcome the limitations of existing therapies will then follow. Most importantly, to the best of our knowledge, this work unprecedentedly combines and discusses all the current advancements in innovative topical patches for the treatment of NMSC. In addition to this, the authors present our insights into the key considerations and emerging trends in the construction of these advanced topical patches. This review is meant for researchers and clinicians to consider utilising advanced topical patch systems in research and clinical trials toward localised interventions of NMSC.

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Development and application of a chromatographic method for simultaneous quantification of 5-fluorouracil and imiquimod in drug-in-adhesive topical patches

Cited by 3 publications

References 32 publications

Development and Optimization of Imiquimod-Loaded Nanostructured Lipid Carriers Using a Hybrid Design of Experiments Approach

Development and Optimization of Imiquimod-Loaded Nanostructured Lipid Carriers Using a Hybrid Design of Experiments Approach

Enhanced Skin Permeation of 5-Fluorouracil through Drug-in-Adhesive Topical Patches

Innovative Topical Patches for Non-Melanoma Skin Cancer: Current Challenges and Key Formulation Considerations

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