Dielectric Thermal Analysis and DSC of Liquid and Solid Pharmaceutical Excipients

摘要

Millions of dollars are expended on pharmaceutical testing to qualify excipients for fully formulated drugs, medicines, active ingredients, containing a full complement of chemical additives or excipients, the inactive ingredients. Individual and interactive properties of excipients and drugs are needed to predict their action in the human body at body temperature 37℃. Dielectric Thermal Analysis [DETA], Differential Scanning Calorimetry [DSC] and Thermal Gravimetric Analysis [TGA] methods are being employed to screen the most widely used drug excipients. In this study the following chemicals were examined by DETA: calcium phosphate, cotton seed oil, croscarmellose, gelatin, mannitol, peanut oil, polyethylene glycol, pioneer sugar, plasdone, sodium alginate, sodium lauryl sulfate, sodium starch glycolate, sodium stearate, a sorbitol solution, canola oil, anhydrous lactose, and benzoic acid. A comparison of DSC and DETA thermal curves based on the same excipient indicates that major endothermic events, e.g. volatilization or melting of the excipient or a drug, are also delineated by fundamental DETA properties, with an exponential rise in permittivity and dielectric loss factor. The focus of this part of the research is to study the "thermal event" response from Dielectric Thermal Analysis, that is, the a.c. electrical conductivity (loss factor frequency constant), permittivity and tan delta (loss factor/permittivity) values vs. frequency. Benzoic acid, a calibrant and considered here as a model drug, melts at 122℃ in the DSC and exhibits orders of magnitude change in permittivity and conductivity at 120-122℃. Canola oil, also a calibrant, defined the lower conductivity chemicals with a conductivity (over a wide range of frequencies) of <1 PS/cm at 37℃ and 2 PS/cm at 100℃. Low temperature properties of liquid excipients reveal endothermic and conductivity changes probably fusion phenomena and glass transitions. Higher temperature properties, for example at 37 and 100℃, of excipients in the DETA, DSC and TGA designate the relative thermal stability or a property change as a function of temperature. The surfactant properties or dipole characteristics of the excipients are reflected in the DETA curves: Conductivity vs. Frequency (100 mHz to 1000 Hz) at a constant temperature, Tan Delta vs. temperature and Tan Delta vs Frequency at a constant temperature as well as Conductivity and Permittivity vs. temperature over a wide range of frequencies. Modification of the surfactant (DETA) properties reveals excipient interactions. Lower electrical conductivity is associated with hydrophobic systems, as observed with the interaction product of benzoic acid and sodium alginate to form glassy solids below their melting temperatures. Higher conductivity suggests enhanced polar content as observed for the interaction of benzoic acid and calcium phosphate. Dielectric analysis employing interdigitated electrodes are a new key physical-analytical method in evaluating real world excipient interactions and possibly predicting performance.