In‐vitro evaluation of performance of solid immediate release dosage forms of weak bases in upper gastrointestinal lumen: experience with miconazole and clopidogrel salts. (1st April 2015)

• Record Type: Journal Article
• Authors: Dimopoulou, Maria; Mourouti, Canella‐Stefania; Vertzoni, Maria; Symillides, Mira; Reppas, Christos
• Other Names: Jones David S guestEditor.; Dressman Jennifer B guestEditor.
• Is Part Of: Journal of pharmacy and pharmacology. Volume 68:Number 5(2016:May)
• Page Start: 579
• Page End: 587
• Publication Date: 2015-04-01
• Subjects: clopidogrel -- miconazole -- salts -- precipitation -- supersaturation; Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/jphp.12406
• Languages: English
• ISSNs: 0022-3573

Abstract

Abstract: Objectives: Evaluate the impact of salt and counterion identity on performance of solid immediate release dosage forms of miconazole and clopidogrel, respectively, in fasted upper gastrointestinal lumen using in‐vitro methodologies. Methods: Two miconazole chemical forms (free base and nitrate salt) and three clopidogrel chemical forms (bisulfate, besylate and hydrochloride salts) were studied. Solubilities of miconazole forms were measured in simulated gastric fluids. Gastrointestinal transfer of the five chemical forms was evaluated by using a flow‐through, three‐compartmental set‐up. Precipitation in duodenal compartment was evaluated by using solutions in gastric compartment. Key findings: Solubilities in simulated gastric fluids, concentrations in duodenal compartment and solubilities in duodenal compartment indicated poorer performance of miconazole nitrate vs. miconazole free base in upper gastrointestinal lumen. In line with the low crystallization tendency of free base, duodenal precipitation of miconazole from a free base solution was limited. Concentrations in duodenal compartment indicated that counterion identity does not affect the performance of clopidogrel; precipitation in duodenal compartment was extensive in all cases. Conclusions: Miconazole data indicate that salts may adversely affect performance of immediate release dosage forms of weak bases. In line with existing in‐vivo data, clopidogrel data indicate that counterion identity is unimportant for the performance of clopidogrel salts in upper intestinal lumen.