Tablet dissolution affected by a moisture mediated solid-state interaction between drug and disintegrant

• Published in: Pharmaceutical research Vol. 16; no. 12; pp. 1850 - 1856
• Main Authors: ROHRS, B. R, THAMANN, T. J, PING GAO, STELZER, D. J, BERGREN, M. S, CHAO, R. S
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01.12.1999; Springer Nature B.V
• Subjects: AIDS/HIV; Biological and medical sciences; Carboxymethylcellulose Sodium - chemistry; Delavirdine - administration & dosage; Delavirdine - chemistry; Drug Stability; Excipients - chemistry; General pharmacology; Magnetic Resonance Spectroscopy; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; Solubility; Spectrophotometry, Infrared; Tablets; Water - analysis; Stability; Disintegration; Vehicle(excipient); Solubility; Molecular interaction; NMR spectrometry; Dissolution; Delavirdine; Infrared spectrometry; Solid state reaction; Water content; Dosage form; Antiviral; Tablet; Physicochemical properties
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/a:1018951309506

To investigate the cause for decrease in delavirdine mesylate 200 mg tablet dissolution upon exposure to high humidity. Dissolution testing was performed using the USP 2 (paddle) apparatus. Water in tablets was measured by Karl Fischer titration. 13C CP/MAS NMR was used to identify and quantify delavirdine form changes in tablets. FT-IR spectroscopy was used to monitor delavirdine form change in tablets and component mixes, and to investigate a solid state reaction with the disintegrant. Dissolution extent of delavirdine mesylate 200 mg tablets was substantially decreased after exposure to high humidity. This effect is related to the amount of water present in the tablet matrix. 13C CP/ MAS NMR detected about 30% conversion from the mesylate salt of delavirdine to its free base form in the tablet matrix. FT-IR spectroscopy demonstrated that a solid state reaction occurs between the freed methanesulfonic acid and the carboxyl sites on the croscarmellose sodium disintegrant. Water is thought to act as both a reaction medium and a plasticizer for croscarmellose sodium, facilitating protonation of the carboxyl sites on the disintegrant. This reaction has the potential to occur for any acid salt of a free base. The limiting solubility of delavirdine free base formed in the tablets accounts for much of the decrease in the extent of dissolution. A change in inter-particle bonding can explain the reduction in tablet deaggregation during dissolution.