Evaluation of a compounding phospholipid base for the percutaneous absorption of high molecular weight drugs using the Franz finite dose model.

BACKGROUND

Permeation-enhancing compounding bases are aimed to facilitate the penetration of the active pharmaceutical ingredients (APIs) across the skin barrier.

OBJECTIVES

The purpose of this study was to evaluate the percutaneous absorption of radiolabeled human insulin ( C-isototpe) when incorporated in a proprietary phospholipid base designed to deliver APIs with high molecular weights (HMW). The aim was not to claim the transdermal delivery of insulin with potential therapeutic applications in diabetes but, instead, to evaluate the ability of the compounding phospholipid base to deliver HMW drugs.

METHODS

The percutaneous absorption of C-insulin was determined using human torso skin and the Franz skin finite dose model. Two topical test formulations were prepared for in vitro evaluation: insulin 1% in phospholipid base (standard) and insulin 1% in phospholipid base HMW. The rate of percutaneous absorption (mean flux) and the distribution of C-insulin through the skin were evaluated for both topical test formulations. A two-way ANOVA was used to determine statistical differences.

RESULTS

The C-insulin was distributed into the stratum corneum, epidermis and dermis. Mean flux values showed a rapid penetration upon application and the maximum flux was achieved at 30 min, followed by a slow decline. Subsequently, a slower decline was observed for the topical test formulation including the phospholipid base HMW.

CONCLUSION

The phospholipid base HMW facilitates the percutaneous absorption of HMW drugs across human cadaver skin and, therefore, it may potentially be a useful option for compounding pharmacists and practitioners when considering the skin for the percutaneous delivery of large drugs.