Factors affecting the morphology of benzoyl peroxide microsponges
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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