Risedronate transdermal delivery system based on a fumaric copolymer for therapy of osteoporosis

- A new membrane base on vinyl acetate-dioctylfumarate copolymer, poly(VA-co-DOF), was prepared.
- Risedronate transdermal drug delivery system (TDDS) for osteoporosis treatment was designed.
- TDDS exhibited good transparence and homogeneous drug distribution, without interaction drug/copolymer.
- Drug release kinetics suggest a complex transport mechanism

Transdermal drug delivery system (TDDS) could be seen as alternative to the oral administration which avoids several adverse effects. In this study a novel TDDS for risedronate (RI), a bisphosphonate used for osteoporosis treatment, based on a vinyl acetate-dioctylfumarate copolymer, poly(VA-co-DOF), previously synthetized, was developed. Two membranes including 6 and 12% (w/w) of drug were obtained, which exhibited good transparence and homogeneous drug distribution, as evaluated by optical microscopy. FTIR spectroscopy and differential scanning calorimetry (DSC) analysis showed no significant drug/polymer interactions, only a plasticizer effect. A new reverse phase high-performance liquid chromatography (RP-HPLC) method for quantification of RI was development and validated, which demonstrate good linearity, reproducibility and accuracy with limits of detection (LOD) and quantification (LOQ) of 0.38 μg/mL and 1.17 μg/mL, respectively. High drug load efficiency and great drug stability were found. The analysis of the drug release kinetics, fitting to Ritger-Peppas model, leads to values of the diffusion coefficient (n) of 1.37 and 1.05, for 6 and 12% (w/w) RI, respectively. These results correspond to super case transport II and suggest a complex transport mechanism, regulated by the mobility of the polymer chains. Together, these results indicate that this new TDDS could be useful for osteoporosis treatment without adverse effect.

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