preparation and evaluation of mouth dissolving films of some anti migraine drugs

Abstract

The aim of this investigation was to develop Rizatriptan (RIZ), Zolmitriptan (ZOL) and Almotriptan (ALMO) mouth dissolving films (MDFs) and evaluate the effect of formulation variables like film thickness, plasticizers, film formers and solubilizing agents on physico-mechanical, chemical and drug release properties of MDFs. MDFs were prepared (using wet film applicator, a commercially scalable technique) using Hydroxy propyl methyl cellulose (HPMC) of different viscosity grades (E3, E5 and E15) as film formers, PEG 400 and glycerol as plasticizers. FTIR studies showed no drug-excipient interactions in the MDF formulations. Photomicrographs together with SEM, DSC and X-RD studies confirmed the absence of RIZ, ZOL and ALMO recrystallization within the MDFs. MDFs of higher film thickness were brittle with low tensile strength values indicating an inverse relationship between film thickness and tensile strength. Whereas, increase in polymer viscosity increased the tensile strength of MDFs. HPMC E15 MDFs showed higher tensile strength compared to E15, and E3. In vitro drug release studies revealed that higher film thickness and polymer viscosities delayed the drug release from MDFs and the release was in the order of E3gtE5gtE15. Addition of solubilizing agents (PVP K30 and SLS) to the E3 formulations resulted faster in drug release compared to formulations without them. Overall, F11 formulation (1% w/w RIZ+7.5% w/w HPMC E3 + 0.04% w/w PVP K30 + 0.5% w/w PEG 400) showed faster disintegration (within 8sec) and RIZ release rates (complete release was obtained in 60sec), F7 formulation (1.25% w/w ZOL+7.5% w/w HPMC E3+0.5% w/w PEG-400+0.04% w/w PVP K30) showed quicker disintegration (within 11sec) and ZOL release rates (within 180sec), and F5 formulation (1.5 % w/w ALMO +7.5% w/w HPMC E3+0.5% w/w PEG-400+0.004 w/w PVP K30) showed quicker disintegration (within 8.66sec) and ALMO release rates (complete release was obtained in 80sec) along with good physico-mechanical properties compared to other formulations.