Esophageal cancer patients are often diagnosed as "advanced" cases. These patients are subjected to palliative stenting using self-expanding metallic stents (SEMS) to maintain oral alimentation. Unfortunately, SEMS get reoccluded due to tumor growth, in and over the stent struts. To investigate potential solutions to this problem, docetaxel (DTX) delivery films were prepared using PurSil AL 20 (PUS), which can be used as a covering material for the SEMS. Drug-polymer miscibility and interactions were studied. Bilayer films were prepared by adhering the blank film to the DTX loaded film in order to maintain the unidirectional delivery to the esophagus. In vitro release and the local DTX delivery were studied using in vitro permeation experiments. It was found that DTX and PUS were physically and chemically compatible. The bilayer films exhibited sustained release (>30 days) and minimal DTX permeation through esophageal tissues in vitro. The rate-determining step for the DTX delivery was calculated. It was found that >0.9 fraction of rate control lies with the esophageal tissues, suggesting that DTX delivery can be sustained for longer periods compared to the in vitro release observed. Thus, the bilayer films can be developed as a localized sustained delivery system in combination with the stent.

Among all the excipients tested, Soluplus dispersion is the most promising candidate for oral formulation development.

No abstract

Docetaxel (DTX) is an anti-cancer compound derived from 10-deacetyl baccatin III which is indicated for treatment of breast, lung, prostate, gastro-esophageal, and head and neck cancers. Epimerization of DTX at the C-7 hydroxyl position has intrigued chemists and has been implicated in loss of potency, as well as in the development of resistance in tumour cells. For localized controlled delivery of this agent, silicone films were prepared from a commercially available silicone kit. High levels of epimeric degradants were unexpectedly found in the in vitro release media. Herein, we discuss this anomalous DTX degradation to epimeric impurities, and discuss the possible reasons for degradation. Systematic stability studies were performed on the release media and the silicone kit components. It was found that release media and tin-based catalyst present in the silicone kit could be responsible for the epimeric conversion. This unusual case of chemical incompatibility can affect product performance and can even lead to development of resistance in tumour cells towards DTX.

PurSil®AL20 (PUS), a copolymer of 4,4'-dicyclohexylmethane diisocyanate (HMDI), 1,4-butane diol (BD), poly-tetramethylene oxide (PTMO) and poly-dimethyl siloxane (PDMS) was investigated for stability as a vehicle for Docetaxel (DTX) delivery through oesophageal drug eluting stent (DES). On exposure to stability test conditions, it was found that DTX release rate declined at 4 and 40 °C. In order to divulge reasons underlying this, changes in DTX solid state as well as PUS microstructure were followed. It was found that re-crystallization of DTX in PDMS rich regions was reducing the drug release at both 4 °C and 40 °C samples. So far microstructural features have not been correlated with stability and drug release, and in this study we found that at 40 °C increase in microstructural domain sizes and the inter-domain distances (from ∼85 Å to 129 Å) were responsible for hindering the DTX release in addition to DTX re-crystallization.