KINETIC ANALYSIS OF IN VITRO DRUG
RELEASE FROM VALPROIC ACID AND SODIUM
VALPROATE SUPPOSITORIES
ADRIANA CIURBA1, NICOLETA TODORAN1*, ALEXANDRINA
TĂUREAN2, PAULA ANTONOAEA1, GABRIEL HANCU3, ANCA
MOISEI4, EMESE SIPOS5
1University of Medicine and Pharmacy of Tîrgu Mureş, Romania, Faculty
of Pharmacy, Department of Pharmaceutical Technology
2University of Medicine and Pharmacy of Tîrgu Mureş, Romania, Faculty
of Pharmacy, Pharmacy no. 3, County Emergency Hospital, Tîrgu Mures
3University of Medicine and Pharmacy of Tîrgu Mureş, Romania, Faculty
of Pharmacy, Department of Pharmaceutical Chemistry
4“Lucian Blaga” University, Sibiu, Faculty of Medicine
5University of Medicine and Pharmacy of Tîrgu Mureş, Romania, Faculty
of Pharmacy, Department of Pharmaceutical Industry and Biotechnology
*corresponding author: nicoleta.todoran@umftgm.ro
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Abstract:

The present study aims to develop new formulations of suppositories containing
valproic acid or sodium valproate for the pediatric use of anticonvulsant therapy. Seven
formulations of valproic acid suppositories have been proposed with four lipophilic
excipients (Suppocire® NAI25, Witepsol® W35, Massa Estarinum E299, Lipex®
403) and three
hydrophilic bases with polyethylene glycol in various ratios (PEG1600 and PEG4000). The
four above-mentioned lipophilic excipients were used to prepare the sodium valproate
suppositories, either in the presence of 5% cetyl alcohol, or of 3% Solutol® HS15, resulting
in 8 liposoluble formulations. Three water-soluble formulations were also made using PEG
basis. The eighteen proposed formulations were studied over a period of 8 hours in terms of
in vitro drug release and diffusion through synthetic membrane. The release kinetics were
evaluated both by independent and time-dependent methods. Akaike Information Criterion
(AIC), used as discrimination criterion, indicated that the most suitable models to describe
kinetics of drug release from the 18 analysed suppository formulations are the Hopfenberg
with Tlag model and the Peppas-Sahlin-2 model.






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