RESUMO
Cancer treatment has improved over the past decades, but a major challenge lies in drug formulation, specifically for oral administration. Most anticancer drugs have poor water solubility which can affect their bioavailability. This causes suboptimal pharmacokinetic performance, resulting in limited efficacy and safety when administered orally. As a result, it is essential to develop a strategy to modify the solubility of anticancer drugs in oral formulations to improve their efficacy and safety. A promising approach that can be implemented is amorphous solid dispersion (ASD) which can enhance the aqueous solubility and bioavailability of poorly water-soluble drugs. The addition of a polymer can cause stability in the formulations and maintain a high supersaturation in bulk medium. Therefore, this study aimed to summarize and elucidate the mechanisms and impact of an amorphous solid dispersion system on cancer therapy. To gather relevant information, a comprehensive search was conducted using keywords such as "anticancer drug" and "amorphous solid dispersion" in the PubMed, Scopus, and Google Scholar databases. The review provides an overview and discussion of the issues related to the ASD system used to improve the bioavailability of anticancer drugs based on molecular pharmaceutics. A thorough understanding of anticancer drugs in this system at a molecular level is imperative for the rational design of the products.
RESUMO
Improving drug solubility is necessary for formulations of poorly water-soluble drugs, especially for oral administration. Amorphous solid dispersions (ASDs) are widely used in the pharmaceutical industry to improve the physical stability and solubility of drugs. Therefore, this study aims to characterize interaction between a drug and polymer in ASD, as well as evaluate the impact on the physical stability and dissolution of alpha-mangostin (AM). AM was used as a model of a poorly water-soluble drug, while polyvinylpyrrolidone (PVP) and eudragit were used as polymers. The amorphization of AM-eudragit and AM-PVP was confirmed as having a halo pattern with powder X-ray diffraction measurements and the absence of an AM melting peak in the differential scanning calorimetry (DSC) curve. The solubility of amorphous AM increased in the presence of either eudragit or PVP due to amorphization and interactions of AM-polymer. Furthermore, FT-IR spectroscopy and in silico studies revealed hydrogen bond interactions between the carbonyl group of AM and the proton of eudragit as well as PVP. AM-eudragit with a ratio of 1:1 recrystallized after 7 days of storage at 25 °C and 90% RH, while the AM-PVP 1:4 and 1:10 samples retained the X-ray halo patterns, even under humid conditions. In a dissolution test, the presence of polymer in ASD significantly improved the dissolution profile due to the intermolecular interaction of AM-polymer. AM-eudragit 1:4 maintained AM supersaturation for a longer time compared to the 1:1 sample. However, a high supersaturation was not achieved in AM-PVP 1:10 due to the formation of large agglomerations, leading to a slow dissolution rate. Based on the results, interaction of AM-polymer in ASD can significantly improve the pharmaceutical properties of AM including the physical stability and dissolution.