Nanocrystalline solid dispersions: an emerging approach for oral bioavailability enhancement of anticancer drugs using lapatinib ditosylate as the case drug

The bioavailability of lapatinib ditosylate, an active anticancer agent against breast neoplasms, is constrained by its poor bioavailability due to poor aqueous solubility. So, the study’s objective was to develop its nanocrystalline solid dispersion (NSD) in order to improve its oral bioavailability. The process of wet media milling followed by lyophilization was used to prepare NSDs of the drug. Using polyvinyl pyrrolidone (PVP), and sodium dodecyl sulfate (SDS) as combination stabilizers, the resultant NSD demonstrated the smallest particle size and a sufficient stability during formulation screening.

Differential scanning calorimetry, and powder X-ray diffraction techniques confirmed the crystalline state of the dispersion. Scanning electron microscopic analysis of optimized NSD revealed evenly distributed rod-shaped crystals of lapatinib ditosylate. The molecular-level interaction in the formulated dispersion was confirmed by NMR analysis. The formulated NSD has enhanced aqueous solubility of lapatinib ditosylate, by 3.68 folds. It also exhibited improved drug release as well as enhanced in vitro anticancer activity in the MCF-7 cell line. Similar findings were derived from in vivo pharmacokinetic investigations, where, compared to pure drug, the maximum plasma drug concentration (C_max), and area under the curve (AUC), of formulated NSD, increased by 2.45, and 2.56, times respectively for lapatinib ditosylate.

All these pharmacokinetic parameters were found to be improved in formulation LP, when compared to the marketed formulation, Tykerb. Thus, this study demonstrated a commercially viable method for increasing the oral bioavailability of anticancer drug, lapatinib ditosylate through the screening and optimization of stabilizers in nanocrystalline solid dispersion.

Read more here

Nanocrystalline solid dispersions: an emerging approach for oral bioavailability enhancement of anticancer drugs using lapatinib ditosylate as the case drug, Preeti Mane,Balaji Wakure & Pravin Wakte, Received 18 Apr 2023, Accepted 13 Nov 2023, Published online: 25 Nov 2023, Cite this article https://doi.org/10.1080/01932691.2023.2284883

Read more on Orally Disintegrating Tablets (ODTs) here: