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

PURPOSE: To investigate the cause for decrease in delavirdine mesylate 200 mg tablet dissolution upon exposure to high humidity. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

USP dissolution apparatus 3 (reciprocating cylinder): instrument parameter effects on drug release from sustained release formulations.

The United States Pharmacopoeia dissolution apparatus 3 (reciprocating cylinder) was evaluated with respect to effects of changes in instrument parameters on drug release rate from six hydrophilic matrix formulations and one coated-bead formulation. Reciprocation rate had the largest effect on time to 50% release for all matrix formulations. Top mesh size had an effect on release rate for those formulations having an erosion component to the drug release mechanism. Bottom mesh size had no effect on release rate. For the coated-bead formulation, no parameter had an effect on release rate. In an assessment of the hydrodynamics of the reciprocating cylinders, conditions equivalent to the 50 rpm paddle and 100 rpm basket were determined to be at the extreme low end of the available reciprocation rate range.