Thermal analytical characterization of mixtures of antipsychotic drugs with various excipients for improved drug delivery

Antipsychotics are a class of psychiatric medication that is primarily effective at reducing psychosis symptoms, particularly in schizophrenia and bipolar disorders. This study aims to formulate mixtures of the antipsychotic drugs quetiapine fumarate (QUE), nortriptyline (NOR), propranolol (PROP) and haloperidol (HAL) with excipients urea, niacin (NIA) and niacinamide (NIM) to obtain an enhanced bioavailability and therapeutic effect. The mixtures were prepared by the solvent method and are characterized by various analytical techniques such as differential scanning calorimetry, wide angle X-ray diffraction, scanning electron microscopy and dissolution studies. Out of the various mixtures that have been prepared and tested, five of them showed eutectic behavior and their eutectic points are as follows: quetiapine fumarate-urea (QUE-UREA) 20-80, w/w; nortriptyline-niacin (NOR-NIA) 70-30, w/w; propranolol-niacin (PROP-NIA) 80-20, w/w; propranolol-niacinamide (PROP-NIM) 40-60, w/w; and haloperidol-niacinamide (HAL-NIM) 20-80, w/w. DSC investigation has revealed the formation of an eutectic system and the phase diagrams and Tamman's triangle construction along with the hot-stage microscopy confirmed their melting points. PXRD study indicated no chemical interaction between either of the mixtures, while SEM study showed the size reduction in these mixtures that has been achieved. In vitro studies of the five mixtures showed an appreciable increase in the dissolution rate compared to that of the drug alone. In conclusion, five simple eutectic mixtures have been formulated by the solvent method and were found to show better dissolution rates than that of the pure form of the drugs, thus improving the bioavailability of these poorly water-soluble drugs.