Compatibility of the antitumoral beta-lapachone with different solid dosage forms excipients.
The objective of the present study was to evaluate the compatibility of the beta-lapachone (betaLAP), an antitumoral drug in clinical phase, with pharmaceutical excipients of common use including diluents, binders, disintegrants, lubricants and solubilising agents. Differential scanning calorimetry (DSC) was used for a first screening to find small variations in peak temperatures and/or their associated enthalpy for six drug/excipient combinations (magnesium stearate, sodium estearyl fumarate, dicalcium phosphate dihydrate, mannitol, randomized methyl-beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin), which indicate some degree of interaction. Additional studies using Fourier transformed infrared spectroscopy (FTIR), optical microscopy (OM) and heating-cooling DSC (HC-DSC) confirmed the incompatibility of betaLAP with magnesium stearate and dicalcium phosphate dihydrate. Those excipients should be avoided in the development of solid dosage forms.
Cunha-Filho
Marcílio S S
MS
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, Santiago de Compostela 15782, Spain.
Martínez-Pacheco
Ramón
R
Landín
Mariana
M
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D004304:Dosage Forms; D004347:Drug Interactions; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry*; D018715:Microscopy, Video; D009285:Naphthoquinones / Q000008:administration & dosage / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
D000972:Antineoplastic Agents, Phytogenic; D004304:Dosage Forms; D005079:Excipients; D009285:Naphthoquinones; C014638:beta-lapachone