Microemulsions and microheterogeneous microemulsion-based polymeric matrices for transdermal delivery of lipophilic drug (Felodipine)

Transdermal administration of drugs is more effective than traditional methods: metabolism of a drug in the gastrointestinal tract and liver is excluded, and its constant concentration in blood is provided. In most cases, the main part of the transdermal patch (TP) is a polymer film (matrix) with good adhesion to skin, which contains a skin permeability enhancer (SPE) and a drug. Types of TPs differ in a way of drug incorporating into the matrix. In this work, a new type of polymer matrices for the delivery of lipophilic drugs based on microemulsions is developed. An optimized direct microemulsion (IV type according to Winsor) is obtained; practically, all its components are SPEs. Microemulsion (ME) type is confirmed by conductometry and dynamic light-scattering methods. Solubilization capacity of ME in relation to the antihypertensive drug felodipine (FEL) is studied. This drug is characterized by poor water solubility and, consequently, by low bioavailability at oral administration (~ 15%). FEL solubility in ME exceeds its solubility in water by 2.2 × 10⁴ times. ME efficiency as a carrier of FEL is shown using Franz diffusion cell and UV spectroscopy. The FEL-loaded microemulsion was used as the dispersed phase of the emulsion, and the dispersion medium of the emulsion was a solution of polymer adhesive (a mixture of polyisobutylenes with different molecular weights and polybutene) in heptane with optimized rheological properties. This emulsified ME (i.e., inverse emulsion) is served as a basis for the microheterogeneous polymer matrix, which provides FEL release at a constant target rate during the day.