Abstract
In the present study Aprepitant (APT) ternary solid dispersions (SDs) were developed and evaluated for the first time. Specifically, ternary SDs of APT with Poloxamer 188 and Soluplus® (SOL) were prepared via melt mixing and compared to binary APT/Poloxamer 188 and APT/SOL SDs. Initially, combined thermo-gravimetric and hot-stage polarized light microscopy studies indicated that all tested compounds were thermally stable up to 280 °C, while Poloxamer 188 acted as a plasticizer to SOL by significantly reducing the temperature required to fully solubilize the API during SD preparation. Differential scanning calorimetry combined with wide angle X-ray diffraction studies showed that crystalline API was dispersed in both binary and ternary SDs, while Fourier transformation-infrared spectroscopy studies revealed no molecular interactions among the components. Scanning electron microscopy combined with EDAX element analysis showed that the API was dispersed in nano-scale within the polymer matrices, while increasing APT content led to increasing API nano-crystals within the SDs. Finally, dissolution studies showed that the prepared formulations enhanced dissolution of Aprepitant and its mechanism analysis was further studied. A mathematical model was also investigated to evaluate the drug release mechanism.
Highlights
Aprepitant (APT), with a chemical name of 5-(((2R,3S)-2-((1R)-1-(3,5-bis(trifluoromethyl) phenyl) ethoxy)-3-(4-fluorophenyl) – 4 morpholinyl) methyl) -1,2 -dihydro-3H -1,2,4 -triazol-3-one, is an antiemetic Active Pharmaceutical Ingredient (API) used for the treatment of chemotherapy induced emesis, nausea and vomiting as well as postoperative nausea and vomiting [1,2]
In the present study the thermal degradation profiles of APT, Poloxamer 188 and SOL were evaluated with the aid of Thermo-Gravimetric Analysis (TGA)
In the case of APT no mass loss is observed up to 246.6 °C, while from that temperature up to 380.0 °C a significant mass loss is observed followed by a second thermal degradation event from
Summary
Aprepitant (APT), with a chemical name of 5-(((2R,3S)-2-((1R)-1-(3,5-bis(trifluoromethyl) phenyl) ethoxy)-3-(4-fluorophenyl) – 4 morpholinyl) methyl) -1,2 -dihydro-3H -1,2,4 -triazol-3-one, is an antiemetic Active Pharmaceutical Ingredient (API) used for the treatment of chemotherapy induced emesis, nausea and vomiting as well as postoperative nausea and vomiting [1,2]. Sci 2019, 1 antagonist of human substance P/neurokinin 1 (NK1) receptors with little or no affinity for serotonin (5-HT3), dopamine and corticosteroid receptors [3,4,5] It is a lipophilic compound supplied in the form of a white to off-white crystalline solid powder with pKa value of 9.7 within the pH range 2 to. APT is categorized as a BCS class IV drug with low aqueous solubility being the rate limiting step for API’s poor gastrointestinal absorption [6,11,12,13]
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