Novel nanosized formulations of two diclofenac acid polymorphs to improve topical bioavailability

Topical application of the anti-inflammatory drug diclofenac (DCF) reduces the severity of systemic unwanted effects compared to its oral administration. A number of transdermal formulations are available on the market and routinely used in clinical and home-care settings. However, the amount of DCF delivered across the skin remains limited and often insufficient, thus making the oral route still necessary for achieving sufficient drug concentration at the inflamed site. In attempting to improve the transdermal penetration, we explored the combined use of DCF nanosuspensions with a microneedle roller. Firstly, DCF nanosuspensions were prepared by a top-down media milling method and characterized by spectroscopic, thermal and electron microscopy analyses. Secondly, the pore-forming action of microneedle rollers on skin specimens (ex vivo) was described by imaging at different scales. Finally, DCF nanosuspensions were applied on newborn pig skin (in vitro) in combination with microneedles roller treatment, assessing the DCF penetration and distribution in the different skin layers. The relative contribution of microneedle length, nanosuspension stabilizer and application sequence could be identified by systemically varying these parameters.

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LC-APCI-MS/MS Quantification and Topical Bioavailability of Chloroacetamide in Rats

Journal of Chromatographic Science ◽

10.1093/chromsci/bmu172 ◽

2014 ◽

Vol 53 (7) ◽

pp. 1100-1106

Author(s):

Tae Hwan Kim ◽

Su Hyun Seok ◽

Kyu-Bong Kim ◽

Beom Soo Shin ◽

Jeong Pyo Lee ◽

...

Keyword(s):

Topical Bioavailability

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HUMAN IN VIVO AND IN VITRO HYDROQUINONE TOPICAL BIOAVAILABILITY, METABOLISM, AND DISPOSITION

Journal of Toxicology and Environmental Health Part A ◽

10.1080/009841098158863 ◽

1998 ◽

Vol 54 (4) ◽

pp. 301-317 ◽

Cited By ~ 39

Author(s):

Ronald C. Wester Joseph Melendres X

Keyword(s):

Topical Bioavailability

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In Vitro Estimates of Topical Bioavailability

Journal of Pharmaceutical Sciences ◽

10.1002/jps.2600660545 ◽

1977 ◽

Vol 66 (5) ◽

pp. 755-757 ◽

Cited By ~ 17

Author(s):

H.Y. Ando ◽

N.F.H. Ho ◽

W.I. Higuchi

Keyword(s):

Topical Bioavailability

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Clotrimazole Loaded Ufosomes for Topical Delivery: Formulation Development and In-Vitro Studies

Molecules ◽

10.3390/molecules24173139 ◽

2019 ◽

Vol 24 (17) ◽

pp. 3139 ◽

Cited By ~ 8

Author(s):

Pradeep Kumar Bolla ◽

Carlos A. Meraz ◽

Victor A. Rodriguez ◽

Isaac Deaguero ◽

Mahima Singh ◽

...

Keyword(s):

Fungal Infections ◽

Entrapment Efficiency ◽

Tape Stripping ◽

X Ray Diffraction ◽

Formulation Development ◽

Scanning Calorimetry ◽

Topical Bioavailability ◽

Diffusion Studies ◽

Permeation Studies

Global incidence of superficial fungal infections caused by dermatophytes is high and affects around 40 million people. It is the fourth most common cause of infection. Clotrimazole, a broad spectrum imidazole antifungal agent is widely used to treat fungal infections. Conventional topical formulations of clotrimazole are intended to treat infections by effective penetration of drugs into the stratum corneum. However, drawbacks such as poor dermal bioavailability, poor penetration, and variable drug levels limit the efficiency. The present study aims to load clotrimazole into ufosomes and evaluate its topical bioavailability. Clotrimazole loaded ufosomes were prepared using cholesterol and sodium oleate by thin film hydration technique and evaluated for size, polydispersity index, and entrapment efficiency to obtain optimized formulation. Optimized formulation was characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). Skin diffusion studies and tape-stripping were performed using human skin to determine the amount of clotrimazole accumulated in different layers of the skin. Results showed that the optimized formulation had vesicle size <250 nm with ~84% entrapment efficiency. XRD and DSC confirmed the entrapment of clotrimazole into ufosomes. No permeation was observed through the skin up to 24 h following the permeation studies. Tape-stripping revealed that ufosomes led to accumulation of more clotrimazole in the skin compared to marketed formulation (Perrigo). Overall, results revealed the capability of ufosomes in improving the skin bioavailability of clotrimazole.

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