Polyaphron Dispersion Technology, A Novel Topical Formulation and Delivery System Combining Drug Penetration, Local Tolerability and Convenience of Application

Abstract

Topical formulation and delivery technologies for pharmaceutical application should simultaneously address efficacy, safety and convenience of therapy. This has historically proven to be challenging, since formulation features that drive efficacy often have undesirable consequences for safety and convenience and vice versa. Polyaphron dispersion (PAD) technology is a novel topical formulation and drug delivery system developed with the purpose of preserving these key attributes. PAD formulations are typically oil-in-water dispersions consisting of oil droplets encapsulated in a multi-molecular shell structure. This shell structure protects potentially unstable active molecules solubilized in the oil from hydrolytic degradation. Example data are presented of enhanced drug penetration from PAD formulations, including dermal delivery of calcipotriene, betamethasone dipropionate and tacrolimus as well as ocular delivery of ciclosporin A. Local tolerability is an important safety parameter for topical formulations, where high levels of surfactants can cause skin irritation. In this regard, a key benefit of PAD formulations is the inherent reduced requirement for surfactants to generate stable formulations compared to conventional emulsion systems. Patients with chronic diseases with topical manifestations such as psoriasis or atopic dermatitis have been reported to miss up to 70% of planned topical applications, mainly due to a lack of satisfaction with their therapy. Patients generally prefer light, moisturizing, non-greasy and quickly absorbed vehicles that are simple to use on all body parts. PAD formulations can generally be designed to meet these criteria. In conclusion, PAD technology provides high flexibility in topical drug design and can be applied to several body locations without compromising efficacy, safety or convenience of therapy. Clinical Trial Register : Clinicaltrials.gov: NCT03802344.

Sensory properties analysis of a calcipotriol and betamethasone dipropionate cream vehicle formulated with an innovative PAD Technology for the treatment of plaque psoriasis on the skin and scalp

“…PAD formulations are manufactured with low levels of surfactant in the water and oil phases, in contrast to conventional emulsions that require a large excess of surfactant in the water phase to maintain physical stability. 12 …”

“…2,3,[9][10][11] Polyaphron dispersion (PAD) technology is a novel oilin-water topical formulation and drug delivery system consisting of oil droplets encapsulated in a multimolecular shell structure. 12 The utilization of PAD Technology to develop a combination of CAL and BDP aqueous cream (CAL/BDP PAD-cream) confers multiple benefits compared with alternative approaches. When compared with anhydrous ointments or suspensions, the presence of a continuous water phase in an oil-in-water cream significantly alters the rheological and sensory attributes that a patient will notice upon application.…”

Spotlight on Calcipotriol/Betamethasone Fixed-Dose Combination in Topical Formulations: Is There Still Room for Innovation?

“…Nowadays, the multi-layer organization is described as a dynamic nanoscale 3D bicontinuous structure involving not only the surfactant, but also bond water and oil [ 31 ].…”

“…This peculiar feature allows avoiding the wash-off of epidermal lipids which leads to the disruption of the skin barrier properties and irritation [ 34 ]. Moreover, the lower the surfactant levels, the lower the solubility of lipophilic drugs, such as Cal and BD, in the aqueous phase; in other words, the overall chemical stability of active ingredients is improved over the storage period [ 31 ]. The cream composition is also responsible for the greater skin flux compared to the marketed Cal/BD oleogel and ointment ( Table 1 ).…”

“…To ameliorate adherence, a model has even proposed to explain the complex interactions among the disease, patient, treatment characteristics, adherence, and outcomes [ 52 ]. Furthermore, validated questionnaires are useful to evaluate the patient’s acceptance of a topical therapy or to compare preferences among formulations [ 31 ].…”