Effect of intra- and extragranular addition of highly porous tribasic calcium phosphate on properties of immediate release acyclovir formulation – Comparison with commercial tablets using compendial and biorelevant dissolution methods

Immediate release, compositionally proportional formulations of acyclovir comprising porous tribasic calcium phosphate were developed and compared with commercial tablets. Comparison of the dissolution behavior was carried out using a compendial method, as well as with the help of a biorelevant dissolution stress test device, which simulates physiological mechanical stress occurring in the gastrointestinal tract. The results showed that the way how tribasic calcium phosphate is used (intra- or extragranular) had an impact on the mechanical properties of tablets as well as their dissolution performance. The dissolution rate of acyclovir from the developed formulations was fast and similar to marketed formulations.

Conclusions
In the presented study a simple formulation of acyclovir tablets was developed. The formulation was proportional in active and inactive ingredients over the whole strength range and made it possible to prepare the 200 mg, 400 mg and 800 mg tablets from the same tableting mixture. Application of the porous excipient, tribasic calcium phosphate (TRI-CAFOS® 500), allowed producing tablets with a short disintegration time and good mechanical properties. The way how TCP was applied (intra- or extragranularly) influenced both the mechanical strength of the tablets as well as their dissolution rate. Intragranular addition resulted in more rapid disintegration and dissolution rate while extragranular one led to obtaining tablets of better mechanical strength. Dissolution study performed both in compendial and biorelevant conditions showed very rapid release and dissolution of acyclovir from developed formulation, favorable and less variable when compared with examined commercial formulations.

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Daniel Zakowiecki, Tobias Hess, Grzegorz Banach, Jadwiga Paszkowska, Grzegorz Garbacz,
Effect of intra- and extragranular addition of highly porous tribasic calcium phosphate on properties of immediate release acyclovir formulation – Comparison with commercial tablets using compendial and biorelevant dissolution methods, Journal of Drug Delivery Science and Technology, Volume 51, 2019, Pages 464-474, ISSN 1773-2247,
https://doi.org/10.1016/j.jddst.2019.03.013