The purpose of this study was to evaluate the potential use of two novel solid formulations of valproic acid (VPA) prepared by complexation with hydrophilic cyclodextrins (CDs) as hydroxypropyl-beta- and sulfobutylether-beta-cyclodextrin and by solid dispersion (SD) in hydrophilic carriers as polyethylene glycol 6000 (PEG 6000) and polyvinylpyrrolidone K-30 (PVP K-30). The corresponding cyclodextrin-based complexes were prepared by the freeze-drying method while the solid dispersions were obtained by the solvent method. Valproic acid solubility improved by CDs complexation and solid dispersion techniques. Comparison of dissolution profiles with that of VPA sodium salt (NaVP) was made by using release parameters such as dissolution efficiency, percent of drug dissolved after 60 min, and difference and similarity factors. Based on difference and similarity factors, it can be concluded that all the VPA formulations possess dissolution profiles essentially equivalent to those of NaVP at pH 6. However, this conclusion is not confirmed by using the analysis of variance (ANOVA) approach, indicating some significant differences between some SD-based formulations and NaVP at that pH value. Preliminary pharmacological studies in the pentylenetetrazole test in rats showed some important differences among the SD-based formulations, NaVP, and VPA as oil/water emulsion. Some implications and limitations of the investigated formulations are discussed.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1081/ddc-120027511 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Persistent low concentrations of antiepileptics in a critically ill paediatric patient: an example of multiple potential drug interactions.
BMJ Case Rep
January 2025
Clinical Pharmacology, Aalborg University Hospital, Aalborg, Region Nordjylland, Denmark
A middle childhood boy with epilepsy exhibited persistent low concentrations of valproic acid, lamotrigine and topiramate for over 1 month, primarily due to pharmacokinetic interactions involving fosphenytoin, meropenem and phenobarbital. Awareness of these clinically significant interactions is crucial for ensuring effective seizure control. However, further research is needed to establish optimal evidence-based treatment strategies in complex paediatric cases.
View Article and Find Full Text PDFThe PPAR-α agonist oleoyethanolamide (OEA) ameliorates valproic acid-induced steatohepatitis in rats via suppressing Wnt3a/β-catenin and activating PGC-1α: Involvement of network pharmacology and molecular docking.
Eur J Pharmacol
January 2025
Pharmacology & Environmental Toxicology, Environmental Studies & Research Institute (ESRI), University of Sadat City, Sadat City 32897, Menoufia, Egypt. Electronic address:
Liver damage is one of the most severe side effects of valproic acid (VPA) therapy. Research indicates that PPAR-α prevents Wnt3a/β-catenin-induced PGC-1α dysregulation, which is linked to liver injury. Although PPAR-α activation has hepatoprotective effects, its role in preventing VPA-induced liver injury remains unclear.
View Article and Find Full Text PDFSodium valproate enhances efficacy of NKG2D CAR-T cells against glioblastoma.
Front Immunol
January 2025
Guangdong Immune Cell Therapy Engineering and Technology Research Center, Center for Protein and Cell-based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Chimeric antigen receptor T-cell (CAR-T) therapies have shown promise in glioblastoma clinical studies, but responses remain inconsistent due to heterogeneous tumor antigen expression and immune evasion post-treatment. NKG2D CAR-T cells have demonstrated a favorable safety profile in patients with hematologic tumors, and showed robust antitumor efficacy in various xenograft models, including glioblastoma. However, malignant glioma cells evade immunological surveillance by reducing NKG2D ligands expression or cleavage.
View Article and Find Full Text PDFMulti-omics analysis to explore the molecular mechanisms related to keloid.
Burns
January 2025
Dermatology Hospital, Southern Medical University, Guangzhou, China. Electronic address:
Background: Keloid is a benign skin tumor that result from abnormal wound healing and excessive collagen deposition. The pathogenesis is believed to be linked to genetic predisposition and immune imbalance, although the precise mechanisms remain poorly understood. Current therapeutic approaches may not consistently yield satisfactory outcomes and are often accompanied by potential side effects and risks.
View Article and Find Full Text PDFValproic acid-induced hyperammonemia with encephalopathy in adults: A meta-analysis.
Int J Clin Pharmacol Ther
January 2025
Objective: Valproic acid, frequently prescribed for neurological and psychiatric disorders, can cause hyperammonemia (HA). This retrospective study aimed to investigate the association among the basic characteristics, comorbidities, co-medications, and risk of HA in patients receiving valproic acid.
Materials And Methods: We compared groups with and without HA using data collected from the medical records of adults undergoing valproic acid monitoring between January 1, 2019, and December 31, 2021.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!