Characterization of piroctone olamine for topical delivery to the skin

Dandruff and its more severe related condition, seborrheic dermatitis affects a high proportion of the population at some point in their life. Piroctone olamine, also known as Octopirox® (OPX) is the monoethanolamine salt of piroctone and is an antifungal agent widely used for the management of dandruff. The aim of the present work was to characterize the physicochemical properties of piroctone olamine and to conduct pre-formulation studies for the development of novel topical formulations of this active.

An HPLC method was developed and validated for the analysis of OPX. The melting point was determined using the DSC Q2000 (TA Instruments, USA). The distribution coefficient (logD_(O/PBS) ) and partition coefficient (log P_o/w ) was determined in phosphate-buffered saline (PBS) AND deionized (DI) water using the shake flask method. All experiments were performed at room temperature. The solubility was determined experimentally by adding amount of active to a solvent. The samples were kept at 32° ± 1°C for 48 h in a water bath. The stability of the compound was determined in a range of solvents by preparing solutions of 1 mg mL^-1 in the relevant solvents. These solutions were kept and stirred throughout the experiment at 32 ± 1°C, and aliquots were taken at 24, 48 and 96 h.

The HPLC method was developed successfully; however, samples at the lower end of the calibration curve showed lower degrees of precision and accuracy. Based on experiments with DSC, the melting point was observed at an onset temperature of 132.4°C. The LogD was determined to be 1.84. The compound had the highest solubility in methanol (278.4 mg mL^-1 ) and propylene glycol (PG), with a value of 248.8 mg mL^-1 . The lowest solubility for OPX was in dimethyl isosorbide (9.9 mg mL^-1 ), Labrafac™ (3.6 mg mL^-1 ) and isostearyl isostearate (0.5 mg mL^-1 ). Over the 4 days, OPX showed stability in ethanol and PG, while a notable decrease in OPX was observed in PBS and DI water at 32 ± 1°C.

The physicochemical properties of OPX were characterized to find suitable excipients able to target the epidermis for topical delivery. Building on these findings, future work will focus on the development of novel topical formulation of OPX.