Preclinical characterisation of NSAIDs in ultradeformable carriers or conventional topical gels

Abstract

We compared in vivo transport and biodistribution of ketoprofen applied on the skin in ultradeformable carriers (Diractin ®) or a conventional topical gel (Gabrilen ®) with oral drug (Oruvail ®); for reference we used in vitro study data. The drug from Gabrilen ® diffuses into body with low bioavailability (<10%) and limited regio-selectivity (AUC(deep muscle/plasma) ∼45/0.8 ( t = 0–8 h), reaching maximum concentration in subcutaneous tissues and plasma at similar time ( t max ∼3–4 h). The apparent drug elimination half-life is then similar to oral ketoprofen ( t 1/2,a ∼2 h). In contrast, Diractin ® containing ultradeformable carriers (Transfersome ® vesicles) delivers the drug more efficiently (>50%) and more directly into peripheral muscles (AUC(deep muscle/plasma) ∼447/0.7 (652/1.4) for t = 0–8 (0–24) h; t max ∼1 h), arguably in non-diffusive fashion. Ketoprofen from Diractin ® moreover disappears from body periphery slower ( t 1/2,a ∼4–6 h), owing to sustained drug release from the carriers in target tissue. Final clearance always proceeds via plasma ( t max ∼4 h). Epicutaneous application of ketoprofen in conventional gels or the carrier-based formulation thus leads to different local accumulations and clearances. Ketoprofen from Diractin ® achieves more desirable biodistribution and clearance, arguably due to spontaneous carrier-mediated drug transport across the skin, which ensures local and relatively long-lasting drug deposition into peripheral target tissues.