Testosterone solid lipid microparticles for transdermal drug delivery. Formulation and physicochemical characterization

Abstract

Purpose: The main objective of the study was to formulate and characterize testosterone (TS) solid lipid microparticles (SLM) to be applied as a transdermal delivery system.

Methods: Testosterone SLMs were formulated using an emulsion melt homogenization method. Various types and concentrations of fatty materials, namely glyceryl monostearate (GM), glyceryl distearate (GD), stearic acid (SA) and glyceryl behanate (GB) were used. The formulations contained 2.5 or 5 mg TS g⁻¹. Morphology, particle size, entrapment efficiency (EE), rheological properties and thermal behaviour of the prepared SLM were examined. In vitro release characteristics of TS from various prepared SLM were also evaluated over 24 h using a vertical Franz diffusion cell. In addition, the effect of storage and freeze-drying on particle size and release pattern of TS from the selected formulation was evaluated.

Results: The results indicated that the type of lipid affected the morphology and particle size of SLM. A relatively high drug percentage entrapment efficiency ranging from 80.7–95.7% was obtained. Rheological studies showed plastic flow characteristics of the prepared formulations. DSC examination revealed that TS existed in amorphous form in the prepared SLM. Release studies revealed the following rank order of TS permeation through cellophane membrane after application of various formulations: 5% GM < 5% GD < 5% SA < 5% GB < 2.5% GM < 2.5% SA < 10% GD < 10% GB. The drug permeation through excised abdomen rat skin after application of 10% GB–2.5 mg TS g⁻¹ SLM was lower than that permeated through cellophane membrane. Moreover, SLM containing 10% GB–2.5 mg TS g⁻¹ stored at 5°C showed good stability as indicated by the release study and particle size analysis. Trehalose showed high potential as a cryoprotectant during freeze drying of the selected SLM formulation.

Conclusions: The developed TS SLM delivery system seemed to be promising as a TS transdermal delivery system.

Key Words: :

• Testosterone
• solid lipid microparticles
• release
• stability
• freeze-drying