JPP 2009, 61: 559–567 ß 2009 The Authors Received September 26, 2008 Accepted February 04, 2009 DOI 10.1211/jpp/61.05.0003 ISSN 0022-3573 Correspondence: Nadia Passerini, Dipartimento di Scienze Farmaceutiche, Universita ` di Bologna, Via S. Donato 19/2, 40127 Bologna, Italy. E-mail: nadia.passerini@unibo.it Research Paper Evaluation of solid lipid microparticles produced by spray congealing for topical application of econazole nitrate Nadia Passerini a , Elisabetta Gavini b , Beatrice Albertini a , Giovanna Rassu b , Marcello Di Sabatino a , Vanna Sanna b , Paolo Giunchedi b and Lorenzo Rodriguez a a Dipartimento di Scienze Farmaceutiche, Universita ` di Bologna, Bologna and b Dipartimento di Scienza del Farmaco, Universita ` di Sassari, Sassari, Italy Abstract Objectives The aims of this study were to evaluate the suitability of the spray congealing technique to produce solid lipid microparticles (SLMs) for topical administration and to study the skin permeation of a drug from SLMs compared with solid lipid nanoparticles (SLNs). Methods Econazole nitrate was used as model drug and Precirol ATO 5 as the lipidic carrier. SLMs and SLNs were both prepared at 5 : 1, 10 : 1 and 12.5 : 1 lipid : drug weight ratios and characterised in terms of particle size, morphology, encapsulation efficiency and chemical analysis of the particle surface. SLMs and SLNs were also incorporated into HPMC K 100M hydrogels for ex-vivo drug permeation tests using porcine epidermis. Key findings SLMs had particle sizes of 18–45 mm, while SLNs showed a mean diameter of 130–270 nm. The encapsulation efficiency was 80–100%. Permeation profiles of econazole nitrate were influenced by both particle size (significant difference until 9 h) and the amount of lipid. Conclusions The results confirm the usefulness of SLNs as carriers for topical administration and suggest the potential of SLMs for the delivery of drugs to the skin. Keywords econazole nitrate; skin delivery; solid lipid microparticles; solid lipid nanoparticles; spray congealing Introduction In recent years, solid lipid micro- and nanoparticles (SLMs and SLNs) have emerged as attractive carriers for topical application in the pharmaceutical and in cosmetic fields because of their advantages over polymeric systems. [1–3] SLNs have been proposed to enhance the percutaneous absorption of drugs [4] and allow drug targeting to the skin. [5–8] Improved dermal absorption of active pharmaceutical ingredients loaded into lipid carriers may result from increases in the surface contact of drug and corneocytes, skin occlusion, rapid and steady release, and surfactant effects. [9] It is well demonstrated that, after application to the skin, the small particles can make close contact with superficial junctions of corneocytes on the outermost skin layers because of a pronounced adhesive effect. [10] Adherence of lipid nanoparticles to the skin leads to the formation of a film and subsequently to an occlusion effect. [11] The first model for film formation by SLNs on the skin was developed by Mu ¨ller and Dingler [12] and the occlusion effect has been widely demonstrated in in-vitro models [13] and after application in vivo. [14] The main approaches used for the production of finely dispersed lipid nanoparticles include high-pressure homogenisation, [15] microemulsions, [16] solvent emulsification– evaporation or –diffusion, [17,18] water/oil/water double-emulsion method [19] and high-speed stirring and/or ultrasonication. [20] SLMs have been less extensively investigated for skin application compared with SLNs but have recently been shown to be potentially useful for both topical and transdermal drug delivery. [21–25] SLMs can be prepared by different processes such as solvent evaporation, melt dispersion, hot and cold homogenisation, spray drying and spray congealing. [26] Spray congealing has 559 Downloaded from https://academic.oup.com/jpp/article/61/5/559/6136005 by guest on 23 January 2023