Acta Pharm. 66 (2016) 191-206
Original research paper
Study of the effect of formulation variables on the
characteristics of combination tablets containing enalapril
maleate and indapamide as active substances using
experimental design
ZOLTÁN-ISTVÁN SZABÓ, BLANKA SZÉKELY-SZENTMIKLÓSI, BOGLÁRKA
DEÁK, ISTVÁN SZÉKELY-SZENTMIKLÓSI, BÉLA KOVÁCS, KATALIN ZÖLDI and EMESE SIPOS
1 Faculty
of Pharmacy, University of Medicine and Pharmacy, RO-540139, Tîrgu Mureș, Romania
2 Gedeon Richter Romania S.A., Technological Development
Department, RO-540306, Tîrgu Mureș, Romania
Accepted October 11, 2015
Published online May 11, 2016
To evaluate the
influence of different variables on tablet formulations containing enalapril maleate and indapamide
as active substances, two separate experimental designs were employed: one for
evaluating powder properties and the other for tablet characteristics. Because
of the low active pharmaceutical ingredient content, it was hypothesized that
both powder and tablet properties could be determined only by the
characteristics of excipients. In order to test this assumption, both
experimental designs were done with placebo mixtures. The optimized formulation
was then evaluated both with and without APIs. Results indicated that filler
and lubricant percentage, along with compression force, were the most important
variables during the formulation study. The optimized formulation showed
similar characteristics in both cases for all responses, except for angle of
repose and friability where only minor differences were observed. The
combination of the applied approaches (using placebo composition and fractional
experimental design) proved to be efficient, cost effective and time saving.
Keywords: design
of experiments, optimization, factorial design, placebo formulation