HTC-15 - Abstract

Abstract Title: Expanding the Application of Thermal Desorber Devices towards Dynamic Headspace Gas Chromatography for the Determination of Residual Solvents
Abstract Type: Seminar
Session Choice: Quantitation, Pharma & Forensics
Presenter Name: Prof Erwin Adams
Co-authors:Mr Adissu Alemayehu Asfaw
Mr Kris Wolfs
Prof Ann Van Schepdael
Company/Organisation: Pharmaceutical Analysis - KU Leuven
Country: Belgium

Abstract Information :

Mesoporous silica (MPSi) and gelatin are frequently used in drug delivery systems. The process usually involves loading of the drug by immersion of the carrier in a drug solution followed by removal of the solvent. Unfortunately, it is practically not possible to remove the solvent completely, which leads to the presence of residual solvents (RS).

Determination of RS is commonly performed using static headspace - gas chromatography (sHS-GC), which is based on the distribution of analytes at equilibrium between the HS and the sample. Although sHS-GC is mainly developed for liquids or solutions of the sample, solids can in principle be processed as well. However, adsorption phenomena like encountered with MPSi make that the equilibrium is no longer purely partition driven. As a result, the relationship between the original concentration of analyte in the sample and the equilibrium concentration in the HS gas phase is highly nonlinear and thus unsuitable for quantitative work. The use of the total or full evaporation approach under HS conditions is also not an option since complete evaporation of the RS from the MPSi can not be guaranteed.

A similar problem arises when RS in drug loaded gelatin samples have to be determined. Indeed, when heated above 50°C in an aqueous environment, gelatin undergoes a physicochemical transformation and loses its solubility in most solvents. So, also here one can not be sure about the complete transfer of the analyte to the vapor phase.

In this work, thermal desorption - gas chromatography - flame ionization detection (TD-GC-FID) is adapted to enable the determination of RS in MPSi and gelatin used for drug delivery. The major modification is related to the sample introduction into the TD tube. Parameters were optimized and validation was performed in terms of sensitivity, linearity, repeatability and recovery. The approach was applied to MPSi loaded with itraconazole using dichloromethane and to gelatin loaded with carbamazepine using DMSO.

To verify the results, alternative methods were developed. For MPSi, this was based on complete dissolution of MPSi in hydrofluoric acid followed by full evaporation HS-GC. For gelatin, the sample was first subjected to enzymatic degradation. Results obtained with the HS-GC methods were found to be similar to those obtained with the TD-GC method, but seen its simplicity and user friendliness, the novel approach is considered to be superior.