title: Small-Scale Assays for Studying Dissolution of Pharmaceutical Cocrystals for Oral Administration.
abstract: The purpose of this study was to better understand the dissolution properties and precipitation behavior of pharmaceutical cocrystals of poorly soluble drugs for the potential for oral administration based on a small-scale dissolution assay. Carbamazepine and indomethacin cocrystals with saccharin and nicotinamide as coformers were prepared with the sonic slurry method. Dissolution of the poorly soluble drugs indomethacin and carbamazepine and their cocrystals was studied with a small-scale dissolution assay installed on a SiriusT3 instrument. Two methodologies were used: (i) surface dissolution of pressed tablet (3 mm) in 20 mL running for fixed times at four pH stages (pH 1.8, pH 3.9, pH 5.4, pH 7.3) and (ii) powder dissolution (2.6 mg) in 2 mL at a constant pH (pH 2). Improved dissolution and useful insights into precipitation kinetics of poorly soluble compounds from the cocrystal form can be revealed by the small-scale dissolution assay. A clear difference in dissolution/precipitation behaviour can be observed based on the characteristics of the coformer used.
authors.affiliation: Sirius Analytical Ltd., Forest Row, East Sussex, UK.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Box
authors.affiliation: Sirius Analytical Ltd., Forest Row, East Sussex, UK.
authors.forename: John
authors.initials: J
authors.lastname: Comer
authors.affiliation: Sirius Analytical Ltd., Forest Row, East Sussex, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Taylor
authors.affiliation: Prosonix, Oxford, UK.
authors.forename: Shyam
authors.initials: S
authors.lastname: Karki
authors.affiliation: Sirius Analytical Ltd., Forest Row, East Sussex, UK.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Ruiz
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Price
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK. n.fotaki@bath.ac.uk.
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Fotaki
mesh_terms: D000284:Administration, Oral; D001681:Biological Assay / Q000379:methods*; D002220:Carbamazepine / Q000737:chemistry; D011232:Chemical Precipitation; D003460:Crystallization; D007213:Indomethacin / Q000737:chemistry; D009536:Niacinamide / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012439:Saccharin / Q000737:chemistry; D012995:Solubility; D013607:Tablets / Q000737:chemistry*
chemical_list: D004364:Pharmaceutical Preparations; D013607:Tablets; D009536:Niacinamide; D002220:Carbamazepine; D012439:Saccharin; D007213:Indomethacin
keywords: carbamazepine; cocrystal; indomethacin; precipitation; small-scale dissolution