A comparative study of Vitamin E TPGS/HPMC supersaturated system and other solubilizer/polymer combinations to enhance the permeability of a poorly soluble drug through the skin

Abstract

In transdermal drug delivery systems (TDDS), it is a challenge to achieve stable and prolonged high permeation rates across skin, because the concentration of the drug dissolved in the matrix has to be high in order to maintain zero order release kinetics of the drug. In case of poorly soluble drugs, due to thermodynamic challenges, there is a high tendency for the drug to nucleate immediately after formulating or even during storage. The present study focuses on the efficiency of vitamin E TPGS/HPMC supersaturated solution and other solubilizer/polymer systems to improve the solubility of the drug and inhibit crystal growth in the transdermal formulation. Effect of several solubilizers, for example, Pluronic F-127, vitamin E TPGS and co-solvent, for example, propylene glycol (PG) were studied on the supersaturated systems of ibuprofen as model drug. Various stabilizers such as hydroxylpropyl methylcellulose (HPMC 3 cps) and polyvinylpyrrolidone (PVP K-30) were examined to evaluate their crystal inhibitory effects. Different analytical tools were used in this study to detect the growth of crystals in the systems. Vitamin E TPGS and HPMC 3 cps formulation produced the highest permeation rate of the drug as compared to other systems. In addition, the onset of crystallization time was shown to be longer with this formulation as compared to other solubilizer/polymer combinations.

Keywords::

• Supersaturated systems
• permeation rate
• vitamin E TPGS
• crystal growth
• synthetic membrane
• porcine skin

Acknowledgements

The authors would like to thank Theresa Bello, Ami Shah (Ernest Mario School of Pharmacy), and Joshua Wang (Biomedical Engineering) for their support with the permeation experiments and HPLC studies.

Declaration of interest

The authors report no conflicts of interest.