Pharmaceutical Technology: Controlled Drug Release, Volume 2
Pharmaceutical Technology: Controlled Drug Release, Volume 2
Pharmaceutical Technology: Controlled Drug Release, Volume 2
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4<br />
Statistical optimization of a controlled release formulation<br />
obtained by a double-compression process: Application of a<br />
Hadamard matrix and a factorial design<br />
A.Peña Romero<br />
Laboratoire de Pharmacie Galénique et Industrielle, UFR de Pharmacie de Grenoble,<br />
Avenue de Verdun, 38243 Meylan, France<br />
J.B.Costa and I.Castel-Maroteaux<br />
Searle Recherche et Développement, Sophia Antipolis, 06560 Valbonne, France and<br />
D.Chulia<br />
Laboratoire de Pharmacie Galénique et Industrielle, UFR de Pharmacie de Grenoble,<br />
Avenue de Verdun, 38243 Meylan, France<br />
SUMMARY<br />
A formulation containing an anti-inflammatory agent (diclofenac sodium), two inert matrices<br />
(ethylcellulose and polyvinyl chloride), a lubricant (magnesium stearate) and talc was optimized<br />
and prepared by a double compression process.<br />
In the first stage, preliminary trials were performed in order to study the effect of lubricant<br />
added before and after precompression.<br />
A Hadamard matrix H(8) was applied to estimate the main effects of four parameters: applied<br />
force at the upper punch (UPF) during precompression, UPF during the final compression, particle<br />
size range after milling and the concentration of ethylcellulose added before the final compression.<br />
According to the Hadamard matrix, a 2 2 factorial design was built. The complete linear models<br />
were fitted by regression for each response, reflecting the compression behaviour and dissolution<br />
kinetics.<br />
Validation was carried out using the area under the dissolution curve, this being the major<br />
response to be optimized. The dissolution curves fitted the Weibull distribution.<br />
INTRODUCTION<br />
Dry granulation is a process which consists of granulating a powder by compression, avoiding the<br />
wetting and drying steps. The advantages and drawbacks of this process were described by Sheth<br />
et al. [1]. The two methods used for dry granulation are compaction and double compression<br />
[2,3].