Nanostructured Composites of Sodium Montmorillonite Clay and PEO Used in Dissolution Improvement of Aprepitant Drug by Melt Mixing

Abstract

In this work, aprepitant (APR) was loaded in a high-molecular-weight poly(ethylene oxide) (PEO) and PEO/clay nanocomposites via the melt-mixing process in order to investigate the combined effect of the PEO and PEO/clay phases on the dissolution profile of APR. Various drug (5, 10, 20 wt %) and Cloisite-Na + microgranuled nanoclay (5 and 10 wt %) loadings were used for the preparation of the solid dispersions using a twin screw melt mixer at temperatures below the drug's melting point. X-ray diffraction (XRD) and infrared (FTIR) data of the prepared formulations confirmed that the semicrystalline structure of the PEO and the structure of APR have remained intact. The PEO chain intercalation in the intragallery space between the clay nanolayers was also confirmed by XRD, especially in the APR/PEO formulations containing 5 wt % microgranuled nanoclay. The in vitro release study demonstrated that in all formulations, the dissolution rate of APR was substantially enhanced compared to neat drug. Immediate release formulations have been prepared, and the combination of PEO/5 wt % clay nanocomposite phase with 5 or 10 wt % drug loading gives much higher maximum dissolution (reaching 98 and 85%, respectively) compared to the neat drug (40%). This improved performance was attributed to the highly intercalated/exfoliated state of clay nanolayers in the APR/PEO/5 wt % clay formulations. A model was also investigated to explain the physical mechanism of drug release in all formulations.

Risperidone Controlled Release Microspheres Based on Poly(Lactic Acid)-Poly(Propylene Adipate) Novel Polymer Blends Appropriate for Long Acting Injectable Formulations

“…The first step is an apparent reaction step, during which the solid API is transformed to its dissolved form, while the second step (highly controlled by stirring intensity) is an external mass transfer step where the dissolved API is transferred into the bulk liquid. In fact, for similar API dissolution trials using the same stirring conditions as the ones selected in the present study, it can be argued that there is no significant contribution of the external mass transfer step and hence the API dissolution process is controlled by the apparent reaction step (e.g., aprepitant [ 41 ], paliperidone [ 42 ], and paclitaxel [ 43 ]). However, this is not the case for risperidone, where initially the API release curve increases very quickly and then continues with a rate which is slower than the one corresponding to first-order kinetics.…”

Evaluation of Dissolution Enhancement of Aprepitant Drug in Ternary Pharmaceutical Solid Dispersions with Soluplus® and Poloxamer 188 Prepared by Melt Mixing

“…Among them, the marketed (under the trade name of Emend ® ) pharmaceutical product utilizes a media nano-milling approach for preparing a hard gelatin capsule containing an effective APT nano-composition at several dosing strengths (40 mg, 80 mg and 125 mg) [6]. Other attempts include the preparation of cyclodextrin complexes [14], nanoparticles [15], liquisolid formulations [16], solid pre-concentrated microemulsions [6] and solid dispersions (SD) [17][18][19][20][21][22][23][24].…”

Physico‐mechanical, rheological and gas barrier properties of organoclay and inorganic phyllosilicate reinforced thermoplastic films

“…Figure 3 represents the XRD patterns of both MMT Na + and cloisite 15A clays and corresponding nanocomposite film samples and the parameters calculated based on (001) reflection plane peaks are summarized in Table 2. From Figure 3(a), it is observed that there is a strong peak at 2 θ = 7.98 ° position corresponding to a d ‐spacing or interlayer spacing of 1.10 nm for MMT Na + nanoclay 44 . After melt mixing with HDPE, the (001) plane peak position shifted to lower angles that means higher d ‐spacing for each sample.…”

“…From Figure 3(a), it is observed that there is a strong peak at 2θ = 7.98 position corresponding to a d-spacing or interlayer spacing of 1.10 nm for MMT Na + nanoclay. 44 After melt mixing with HDPE, the (001) plane peak position shifted to lower angles that means higher d-spacing for each sample. A similar trend is also observed for HDPE/cloisite 15A nanocomposite films where a strong peak at 2.75 position with the d-spacing of 3.21 nm 45 shifted to lower angles which correspond to higher d (001) for each sample.…”