Benzoyl Peroxide Development, Pharmacology, Formulation and Clinical Uses in Topical Fixed-combinations

Benzoyl peroxide (BPO) is one of the most commonly prescribed topical anti-acne agents.¹ BPO is arguably the most versatile with the longest history of successful use for acne. More than 100 topical BPO products are available both by prescription and over-the-counter in the United States (U.S.), with concentrations ranging between 2.5% and 10%. The safety and efficacy of BPO have been established over many years of study as both monotherapy and in combination with a variety of other acne treatments.^2,3

Two important clinical implications when using BPO are concentration and formulation. Early preparations contained water and organic and mineral components, but lacked stability and degraded to subtherapeutic levels after approximately four months.4 Initial attempts to stabilize these preparations with antioxidants inhibited BPO activity. Thus, early BPO formulations required mixing immediately before use. However, it was discovered that if the vehicle contained only water and an inert organic emollient, the BPO neither degraded nor reacted with the other components of the formulation. In 1980, Fulton obtained a patent for a topical BPO stabilized with glycerol, which produced a soft, viscous gel.⁵ Stability and shelf life were further improved with the development of micronized BPO in an aqueous or hydro-alcoholic vehicle. Furthermore, utilization of an optimized aqueous vehicle and micronized BPO had the benefit of reducing the irritation associated with BPO use because of the lower concentration of BPO required for efficacy.^3,4,6 These technological advances have allowed BPO to become one of the most frequently used and beneficial agents for the treatment of acne.

Topically-applied BPO has antibacterial, keratolytic, comedolytic and anti-inflammatory activity,^{2,3,7–10} the most important of which is arguably its antibacterial action. Not only is its activity against Propionibacterium acnes (P. acnes) rapid, bacteriostatic and bactericidal,¹¹ but it also seems to protect against development of bacterial resistance of co-administered antibiotics.^11,12 So far, there is no evidence of P. acnes resistance to BPO.^2,8,11,12

Skin irritation and dryness can be a problem with BPO. The use of BPO formulations with strengths of 5% and higher have not been shown to provide any significant efficacy benefit over lower concentrations, but cutaneous tolerability is largely dosedependent and tends to be less favorable at increasing concentrations. Formulation properties also play a key role in the efficacy and tolerability delivered.

The bacteriostatic activity of BPO against P. acnes was identified in 1974,⁵ and later Cove and Holland found that BPO had potent bactericidal action against eight microorganisms that commonly colonize skin.¹³ In studies comparing P. acnes recovery from the sebum of 10 subjects who had applied BPO 10% in an alcohol gel vehicle and vehicle alone twice daily, there was a marked reduction of bacterial levels in the sebum of those using the BPO gel.¹⁴ Other antibacterial effects that have been identified are: inhibition of bacterial cell metabolic function; alteration of protein synthesis; DNA strand breakage; and suppression and interference of mitochondrial synthesis and respiration. This wide range of effects may explain why bacteria have not yet developed resistance to BPO.¹⁵