Cubosomal based oral tablet for controlled drug delivery of telmisartan: formulation, in-vitro evaluation and in-vivo comparative pharmacokinetic study in rabbits

Abstract

A nanoparticulate system; cubosomes has been suggested to support the controlled release of Telmisartan (TEL), a poorly water-soluble medication. Four distinctive formulae were selected according to the results of three estimated responses. The liquid cubosomes were successfully adsorbed onto Aerosil 380 to form granules. The formulae were evaluated for their flow properties. The best granules were compressed into tablets suitable for oral administration. The tablets were evaluated for its performance. The in vivo study of the best selected cubosomal tablets was checked after oral administration in the blood of albino rabbits utilizing an HPLC method. Results revealed that the highest EE was shown in formulae C5 (59.68 ± 1.3). All the prepared formulae had particle size less than 500 nm with PDI < 0.5 and the highest zeta potential results were observed in C5, C7, C9, C11 and C12 (>30 mv). A7 and A9 prepared using Aerosil 380 showed a perfect flowability. After 1 h of dissolution testing, the commercial product showed a 66% drug release while the release of all cubosomal formulae didn't exceed 35% during the first hour reaching a 85% of the drug released at the end of 24 h. A7 was selected for the in vivo study; T_max of TEL absorption is increased for cubosomal formula by three folds indicating sustained release pattern. The relative bioavailability is also increased by 2.6 fold. The investigation proposed the rationality of cubosome to figure an effective controlled release tablets to improve its bioavailability and expand its activity.

Keywords: Cubosomes; Telmisartan; bioavailability; experimental design; sustained-release tablet.