Nanocrystals can enhance skin penetration of drug by increased saturation solubility, dissolution rate and adhesion on the skin. Apremilast is ‘difficult-to-deliver’ in viable layers (epidermis, dermis) and stratum corneum (SC) owing to its poor aqueous solubility and modest lipophilicity, respectively. Apremilast is currently available as oral tablet formulation for the indication of psoriasis but its effectiveness is limited by systemic side effects. Therefore, the present study aimed to develop novel nanocrystal-based formulations of apremilast for improved topical delivery. Nanosuspension was prepared using wet media milling and exhibited a mean particle size of 200 nm. The saturation solubility of nanocrystals was improved by 2-fold than micronized apremilast and showed significant advantage during dissolution study. Nanosuspension and micronized apremilast was incorporated into gel and cream and characterized for rheological properties. Skin permeation and ex vivo dermatokinetic study of topical formulations were performed on pig ear skin at a dose of 1% w/w using Franz diffusion cells. Skin permeation studies indicated that non-detectable amount of apremilast permeated through pig ear skin during exposure of formulations. Nanosuspension showed 2.6- and 3.2-fold drug penetration in SC and viable layers, respectively, over microsuspension. Nanogel showed 2.7- and 2.4-fold drug penetration in SC and viable layers, respectively, over microgel. Nanocream showed 1.2- and 2.8-fold drug penetration in SC and viable layers, respectively, over microcream. Thus, nanocrystal-based formulations of apremilast aid in selective delivery into viable layers by crossing the SC barrier. This is of paramount importance in enhancing therapeutic effectiveness utilizing localized delivery and provides an alternative delivery approach for the treatment of psoriasis.
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Prashantkumar K. Parmar would like to gratefully acknowledge Rajiv Gandhi National Fellowship (RGNF, New Delhi, India) for providing Ph.D. Scholarship. Prashantkumar K. Parmar would also like to thank Sonu Dalsania, Pooja Sharma, Dnayaneshwar Kale, Payal Sharma and Jhanvi Wadhawan for their support and help during this project. The authors would like to acknowledge NIPER - S.A.S. Nagar for providing necessary facilities for this project.
The authors declare that they have no conflicts of interest.
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Parmar, P.K., Bansal, A.K. Novel nanocrystal-based formulations of apremilast for improved topical delivery. Drug Deliv. and Transl. Res. (2020). https://doi.org/10.1007/s13346-020-00809-1
- Topical delivery