Lean production of taste improved lipidic sodium benzoate formulations

• Published in: European journal of pharmaceutics and biopharmaceutics 2014-10, Vol.88 (2), p.455-461
• Main Authors: Eckert, C., Pein, M., Breitkreutz, J.
• Format: Article
• Language: English
• Subjects: Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Electronic tongue; Food interaction; Hard fat; Lipids - chemistry; Melt granulation; Microscopy, Electron, Scanning; Orphan drug; Pharmacokinetics; Sodium benzoate; Sodium Benzoate - chemistry; Solubility; Taste; Taste masking; Tongue
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2014.05.013

[Display omitted] •Reproducible granulation process with a power value based endpoint.•Fast dissolving minitablets were produced using hard fat as sole excipient.•Taste improvement of all formulations was confirmed by e-tongue measurements.•Precise and accurate dosing is feasible using a special dosing spoon. Sodium benzoate is a highly soluble orphan drug with unpleasant taste and high daily dose. The aim of this study was to develop a child appropriate, individually dosable, and taste masked dosage form utilizing lipids in melt granulation process and tableting. A saliva resistant coated lipid granule produced by extrusion served as reference product. Low melting hard fat was found to be appropriate as lipid binder in high-shear granulation. The resulting granules were compressed to minitablets without addition of other excipients. Compression to 2mm minitablets decreased the dissolved API amount within the first 2min of dissolution from 33% to 23%. The Euclidean distances, calculated from electronic tongue measurements, were reduced, indicating an improved taste. The reference product showed a lag time in dissolution, which is desirable for taste masking. Although a lag time was not achieved for the lipidic minitablets, drug release in various food materials was reduced to 2%, assuming a suitable taste masking for oral sodium benzoate administration.