吡罗克酮乙醇胺用于皮肤局部给药的特性研究。

Characterization of piroctone olamine for topical delivery to the skin.

机构信息

UCL School of Pharmacy, London, UK.

Unilever R&D Port Sunlight, Bebington, UK.

出版信息

Int J Cosmet Sci. 2023 Jun;45(3):345-353. doi: 10.1111/ics.12839. Epub 2023 Mar 27.

DOI:10.1111/ics.12839

PMID:36752028

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10947268/

Abstract

OBJECTIVE

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.

METHODS

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 ) and partition coefficient (log P ) 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 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.

RESULTS

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 ) and propylene glycol (PG), with a value of 248.8 mg mL . The lowest solubility for OPX was in dimethyl isosorbide (9.9 mg mL ), Labrafac™ (3.6 mg mL ) and isostearyl isostearate (0.5 mg mL ). 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.

CONCLUSION

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.

摘要

目的

头皮屑及其更严重的相关疾病——脂溢性皮炎在人群中的很大一部分人一生中的某个阶段都会受到影响。吡罗克酮乙醇胺，也称为奥克立林（OPX），是吡罗克酮的单乙醇胺盐，是一种广泛用于治疗头皮屑的抗真菌剂。本工作的目的是表征吡罗克酮乙醇胺的物理化学性质，并为该活性物质的新型局部制剂的开发进行预配方研究。

方法

开发并验证了一种用于分析 OPX 的 HPLC 方法。使用 DSC Q2000（TA 仪器，美国）测定熔点。使用振摇瓶法在磷酸盐缓冲盐水（PBS）和去离子（DI）水中测定分配系数（logD）和分配系数（log P）。所有实验均在室温下进行。通过向溶剂中添加一定量的活性物质来实验确定溶解度。将样品在 32°±1°C 的水浴中保持 48 h。通过在相关溶剂中制备 1 mg·mL 的溶液来确定化合物在一系列溶剂中的稳定性。这些溶液在整个实验过程中保持在 32°±1°C 并搅拌，并在 24、48 和 96 h 时取等分试样。

结果

成功开发了 HPLC 方法；然而，校准曲线低端的样品显示出较低的精密度和准确度。根据 DSC 实验，观察到起始温度为 132.4°C 时的熔点。确定 LogD 为 1.84。该化合物在甲醇（278.4 mg·mL）和丙二醇（PG）中的溶解度最高，值为 248.8 mg·mL。OPX 的最低溶解度为二甲基异山梨醇（9.9 mg·mL）、Labrafac™（3.6 mg·mL）和异硬脂酸异硬脂酸酯（0.5 mg·mL）。在 4 天内，OPX 在乙醇和 PG 中表现稳定，而在 32°±1°C 的 PBS 和 DI 水中，OPX 明显减少。