Stability and In Vitro Skin Compatibility of an Adapalene-Loaded Solid Lipid Microparticle Dispersion

Muller-Goymann Cc,Lauterbach A,Fuller J

doi:10.21767/2469-6692.10004

Abstract

A novel adapalene-loaded solid lipid microparticle (SLMA) dispersion composed of topically approved ingredients exhibited follicular penetration and a targeted drug release in sebum. In the present study, the stability regarding particle size, thermoanalytical properties, drug content, and pH value was tested after storage at 5°C, 23°C, and 40°C over 12 weeks. Additionally, a thermal cycling study was performed in order to consider storage temperature variations. The dermal compatibility was tested on a HaCaT monolayer in comparison to the Differin® cream in order to evaluate potential local side effects. The SLMA dispersion displayed a pronounced physical stability at 5°C including a constant particle size as well as melting point. Compared to that, the physical stability was limited at 40°C with significant particle growth and a significantly increased melting temperature, whereas the properties just slightly changed during storage at 23°C. The drug content and pH value remained the same. The skin compatibility test revealed a high cell viability of about 90% for all investigated dilutions of the SLMA dispersion probably due to the presence of glycerides and lecithin. On the contrary, the dilutions of the Differin® cream caused a significant decrease of the cell viability to approximately 11% based on its ingredients.

Highlights

A novel adapalene-loaded solid lipid microparticle (SLMA) dispersion composed of 13.93% hydrogenated palm oil, 5.97% purified lecithin, 0.1% adapalene, 12% poloxamer 407 (P407), 3% polyethylene glycol 12000, 0.2% potassium sorbate, 0.1% citric acid, and 64.7% water of double-distilled grade featured follicular penetration, erosion in sebum lipids and a superior drug release in sebum compared to the commercial cream
The cell viability was compared between the SLMA dispersion and the Differin® cream on a HaCaT monolayer by performing an MTT test
The SLMA dispersion showed an enhanced physical stability at 5°C since the particle size remained in the range of 3.5 to 3.7 μm, the particle size distribution was narrow between 1 and 10 μm (Fig. 1), and the the melting onset temperature (Tonset) of about 55°C and Trecryst of approximately 28°C were nearly the same over 12 weeks (Table 1)

Summary

Introduction

A novel adapalene-loaded solid lipid microparticle (SLMA) dispersion composed of 13.93% hydrogenated palm oil, 5.97% purified lecithin, 0.1% adapalene, 12% poloxamer 407 (P407), 3% polyethylene glycol 12000, 0.2% potassium sorbate, 0.1% citric acid, and 64.7% water of double-distilled grade (all by weight) featured follicular penetration, erosion in sebum lipids and a superior drug release in sebum compared to the commercial cream. Further convenient attributes are the physical and chemical stability regarding particle size, melting behavior, and drug content at ambient storage conditions, and the utilization of safe inactive ingredients for dermal application. The SLMA dispersion was subjected to a stability study at 5°C, 23°C, and 40°C over 12 weeks as well as a thermal cycling sequence including three cycles comprising alternating storage at 5°C and 40°C each for 2 days. The cell viability was compared between the SLMA dispersion and the Differin® cream on a HaCaT monolayer by performing an MTT test

Materials and Methods

Results and discussion

Conclusion