The application of microwave heating methods in pharmaceutical formulations

摘要

This study investigated the potential application of formulating pharmaceutical products using microwave heating methods alongside associated analytical investigations. Firstly, the interaction between three functionally related drugs, ibuprofen, ketoprofen and flurbiprofen, with two distinct forms of cyclodextrin at three temperatures, 298, 303 and 310K was investigated using isothermal titration calorimetry (ITC). In all cases, the associated changes in Gibbs free energy, enthalpy, and entropy are presented along with the stoichiometry and binding constant. It was found that binding always occurred at a 1:1 ratio with an associated negative enthalpy and Gibbs free energy with the formation of the complex enthalpically, rather than entropically driven. The data further demonstrated a clear relationship between the thermodynamic behaviour and logP of the drug molecules and provides an insight into the chemistry of drug-excipient binding for the compounds under investigation in this work. Secondly, four drugs, ibuprofen, ketoprofen, flurbiprofen and paracetamol were formulated using microwave and conventional heating, with and without the presence of water, with four excipients, namely, stearic acid (SA), β-cyclodextrin (BCD), 2-(hydroxypropyl)-β-cyclodextrin (2HPBCD) and polyvinylpyrrolidone (PVP). Three different analytical techniques were employed to determine whether the formulation method made a significant difference to the appearance and behaviour of the product. For example, the thermal behaviour of the drug and excipient, was investigated by differential scanning calorimetry (DSC). Scanning electron microscopy was utilised to determine if the formulation method illustrated any physical differences between the formulations and lastly, a thermal activity monitor was used to investigate the stability of the different formulations. Overall, it was found that the formulation method can make a significant difference to the character of the resultant formulations with a change in thermal behaviour or physical appearance observed in certain formulations but with a consistent stability seen across all products. Lastly, each of the resultant formulations were subjected to dissolution analysis to determine if the presence of water or choice of heating method, i.e. conventional heating vs. microwave heating affected the dissolution profile obtained. It was found that in the majority of cases water increased drug dissolution, which may have occurred because of a reduction in particle size. In summary, the application of microwave heating for pharmaceutical formulations has been thoroughly investigated and found to be a potential alternative to conventional heating with several distinct benefits for industry and the patient.