Effect of stearic acid on enalapril stability and dissolution from multiparticulate solid dosage forms
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Data
2013-09
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Resumo
Enalapril maleate (EM) is a widely used anti-hypertensive drug which is unstable when mixed
with excipients. Enalaprilate and diketopiperazine (DPK) are the main degradation products of enalapril.
The in situ preparation of enalapril sodium salt (NaE) has been used to improve drug stability in dosage
forms; however, gas release and product rejection ensue when the chemical reaction for obtaining the
sodium salt is not completely finished before packaging. This study evaluated the effect of stearic acid
(SA) on enalapril stability in microcrystalline cellulose (MCC) pellets containing EM or NaE. MCC
pellets containing SA were prepared by the extrusion–spheronization technique and characterized.
Enalapril stability and dissolution were then evaluated. DPK and enalaprilate formation were reduced
by the addition of SA in pellets containing EM. The overall enalapril degradation in these formulations
was lower when compared with pellets containing EM or even NaE prepared without SA. The immediate release characteristic was maintained by the addition of 5% crospovidone to all the formulations tested.
The incorporation of SA into NaE pellets resulted in unexpected enalapril degradation, caused by the
interaction of these compounds, as suggested by a thermal analysis of the SA–NaE binary mixture. The
findings presented here showed that formulations containing SA could substitute the formation of NaE,
since they provide better enalapril stability in solid dosage forms. In addition, it is suggested that the
stabilization effects would be observed for other N-carboxyalkyl dipeptide analogs with angiotensin
converting enzyme inhibition activity, since these new entities share the same degradation pathway of
enalapril.
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Palavras-chave
Diketopiperazine, Stearic acid., Enalaprilate, Extrusion–spheronization, Enalapril
Citação
CUNHA, Talita A. et al. Effect of stearic acid on enalapril stability and dissolution from multiparticulate solid dosage forms. AAPS PharmSciTech, New York, v. 14, n. 3, p. 1150-1157, Sept. 2013.