Elsevier

Micron

Volume 38, Issue 8, December 2007, Pages 834-840
Micron

Factors affecting the morphology of benzoyl peroxide microsponges

https://doi.org/10.1016/j.micron.2007.06.012Get rights and content

Abstract

Benzoyl peroxide (BPO) is primarily used in the treatment of mild to moderate acne. However, its application is associated with skin irritation. It has been shown that encapsulation and controlled release of BPO could reduce the side effect while also reducing percutaneous absorption when administered to the skin. The aim of the present investigation was to design and formulate an appropriate encapsulated form of BPO, using microsponge technology, and explore the parameters affecting the morphology and other characteristics of the resultant products employing scanning electron microscopy (SEM). Benzoyl peroxide particles were prepared using an emulsion solvent diffusion method by adding an organic internal phase containing benzoyl peroxide, ethyl cellulose and dichloromethane into a stirred aqueous phase containing polyvinyl alcohol (PVA). Different concentrations of BPO microsponges were incorporated in lotion formulations and the drug release from these formulations were studied. The SEM micrographs of the BPO microsponges enabled measurement of their size and showed that they were spherical and porous. Results showed that the morphology and particle size of microsponges were affected by drug:polymer ratio, stirring rate and the amount of emulsifier used. The results obtained also showed that an increase in the ratio of drug:polymer resulted in a reduction in the release rate of BPO from the microsponges. The release data showed that the highest and the lowest release rates were obtained from lotions containing plain BPO particles and BPO microsponges with the drug:polymer ratio of 13:1, respectively. The kinetics of release study showed that the release data followed Peppas model and the main mechanism of drug release from BPO microsponges was diffusion.

Introduction

Benzoyl peroxide is commonly used in topical formulations for the treatment of most forms of acne and, more recently, athlete's foot. It is a first-line topical treatment in acne vulgaris and is superior to antibiotics because the bacteria do not develop resistance to this drug, and it is preferred over keratolytic agents due to its bactericidal effect. However, its use can cause mild skin irritation and dryness. The degree of irritation is believed to be related to the amount of BPO present in the product (Fulton and Bradley, 1974). It has been shown that encapsulation of benzoyl peroxide can reduce the side effects to a great extent (Arabi et al., 1996). For example, it has been shown that the controlled release of BPO reduced skin irritation due to the reduction in release rate of the drug from formulation (Arabi et al., 1996, Lorenzetti et al., 1977, Wester et al., 1991). The encapsulated form has received increasing attention as a means for controlled release purpose (Puranik et al., 1992).

One of the techniques used to slow down the release of active ingredients from topical formulations is microsponge delivery (Jelvehgari et al., 2006). This technology has recently been reviewed comprehensively by Chadawar and Shaji (2007). Microsponges are polymeric delivery systems composed of porous microspheres. They are tiny sponge like spherical particles that consist of myriad of interconnecting voids within a non-collapsible structure with large porous surface. The size of these microsponges can be varied, usually from 5 to 300 μm in diameter depending on the degree of smoothness. However, by optimising formulation parameters such as drug:polymer ratio and agitation/stirring rate it might be possible to manufacture nanosponge drug delivery systems. A typical microsponge bead is a ca. 25 μm sized sphere which can have up to 250,000 pores and an average internal pore structure equivalent to 10 ft in length and average pore volume of about 1 ml/g. The surface can be varied from 20 to 500 m2/g and pore volume range from 0.1 to 0.3 cm3/g.

Prepared benzoyl peroxide microsponge formulations can clearly increase the period of time in which active ingredient remain on the skin surface or within the epidermis while minimizing its penetration through the dermis and, therefore, into the body. This system provides maximum efficacy, minimum irritancy, extended product stability and improved aesthetic properties in an efficient and novel delivery system.

It is increasingly becoming acceptable that nanostructure-mediated drug delivery has the potential to enhance bioavailability, improve controlled release of drugs, and enable precision targeting the drug to the site of disease or infection (Dubin, 2004, Mozafari, 2006). Therefore, work on the large-scale and reproducible preparation of similar formulations of BOP in nano-dimensions is ongoing in our laboratory. Nevertheless, recently it has been suggested that “nanotechnology” includes “microtechnology” and “nanofabrication” or “nanomanufacturing” and its micro-counterparts (Park, 2007). Although the end product of the present research work is currently in micro-domain – while it is a positive move towards manufacture of nanostructures – the methodology used in the preparation of the novel formulations of BPO and the high-resolution imaging technique used for the characterisation of the particles are in the realm of nanotechnology as defined by Park (2007).

We have already investigated the parameters affecting the preparation of benzoyl peroxide microsponges and loading factors (Jelvehgari et al., 2006). In the present study, investigation was focused on exploring the factors affecting the morphology and size of these particles using scanning electron microscope. The kinetics of drug release from these particles incorporated in lotion formulations was also studied.

Section snippets

Materials and methods

Benzoyl peroxide, polyvinyl alcohol (MW = 10,600–11,000), dichloromethane, acetone, methanol, polyethylene glycol 400, and benzophenon, liquid paraffin, triethanolamine, and stearic acid were all from Merck (Darmstadt, Germany). Ethyl cellulose (48 cP 5 wt.% solution in 80/20 toluene/ethanol) was purchased from Sigma–Aldrich (St Louis, USA). White beeswax was purchased from Thornton and Ross (Huddersfield, England). All other chemicals and solvents were of analytical grade.

Results and discussion

Scanning electron microscopy of the pure benzoyl peroxide and its microsponge forms are shown in Fig. 1. It is clear from the figure that microsponges have predominantly spherical shape and contain orifices (Fig. 1b–f) in comparison with the original benzoyl peroxide particles (Fig. 1a). These orifices caused by the diffusion of the solvent (dichloromethane) from the surface of the microparticles. The type and concentration of emulsifier has a key role to play in the preparation of

Conclusion

Results of this work showed that changes in particle size and morphology of the microsponge systems have a big impact on different crucial properties such as porosities, drug release and kinetics of drug release. The present study showed that by careful control of the process parameters microsponge particles with desirable properties can be produced. Towards this end, scanning electron microscopy proved to be an indispensable equipment in the characterization and rational formulation of various

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