Using Self-Nanoemulsifying System to Improve Oral Bioavailability of a Pediatric Antiepileptic Agent Stiripentol: Formulation and Pharmacokinetics Studies

Dai, Qiuyang; Zhang, Peiyan; Jin, Yilan; Mi, Tang; Shen, Mengling; Xu, Shujun; Huang, Susu; Chen, Yong

doi:10.1208/s12249-020-01730-z

Cited by 6 publications

(10 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chemical stability assays at the physiologic conditions the drug will be exposed to are also very important, particularly when SEDDS are loaded with chemically labile drugs. A clear example of this is depicted in the Dai et al [ 36 ] study. They formulated stiripentol, an acid-labile antiepileptic drug, in a SNEDDS to increase bioavailability after oral administration.…”

Section: Sedds Development For Delivery Of Neurotherapeutics Agents T...mentioning

confidence: 89%

“…After an 8 h exposure of either a methanolic stiripentol solution or a stiripentol SNEDDS to a 0.1 M HCl solution, only 37.48% of stiripentol remains in the methanolic solution. On the contrary, when formulated in a SNEDDS, stiripentol percentage was kept at 97% after 8 h of experimentation, demonstrating the ability of these lipidic nanosystems in protecting acid-labile drugs from degradation [ 36 ].…”

Section: Sedds Development For Delivery Of Neurotherapeutics Agents T...mentioning

confidence: 99%

“…A small number of SEDDS-based products have already been successfully introduced into the pharmaceutical market, with none of them loading drugs for the treatment of neurological disorders. Until now, several in vivo assays using oral SEDDS have been carried out for neuropharmaceuticals brain targeting [ 4 , 6 , 23 , 24 , 25 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 70 ], but only a few in vivo pre-clinical studies have been reported for IN administration of neurotherapeutics loaded in SEDDS. In fact, only six studies were found that investigated the IN administration of neurotherapeutics loaded in SEDDS: clonazepam [ 45 ], diazepam [ 44 ], and perampanel [ 28 ] for epilepsy treatment; Bdph for glioblastoma treatment [ 4 ]; huperzine A [ 30 ] for Alzheimer’s disease; and naringin [ 5 ] as a neuroprotective for Alzheimer’s and Parkinson’s disease.…”

Section: Application Of Sedds In Brain Drug Delivery—pre-clinical Stu...mentioning

confidence: 99%

“…To overcome some mutual limitations regarding antiepileptics oral administration, SEDDS were demonstrated to be a reliable alternative ( Table 2 ). In fact, to overcome both low aqueous solubility, gastrointestinal instability, and GIT low permeability, lamotrigine, stiripentol, and carbamazepine were formulated as oral SNEDDS or SMEDDS [ 23 , 36 , 43 ]. For the three cases, both plasmatic C max and AUC 0-t significantly increased compared with traditional oral formulations, which explains the obtained relative bioavailability higher than 100% ( Table 2 ) [ 23 , 36 , 43 ].…”

Section: Application Of Sedds In Brain Drug Delivery—pre-clinical Stu...mentioning

confidence: 99%

“…In fact, to overcome both low aqueous solubility, gastrointestinal instability, and GIT low permeability, lamotrigine, stiripentol, and carbamazepine were formulated as oral SNEDDS or SMEDDS [ 23 , 36 , 43 ]. For the three cases, both plasmatic C max and AUC 0-t significantly increased compared with traditional oral formulations, which explains the obtained relative bioavailability higher than 100% ( Table 2 ) [ 23 , 36 , 43 ]. Cannabidiol, the well-known therapeutic compound of the Cannabis sativa plant, was also formulated in a patented Swiss SEDDS technology—VESIsorb ® (SourceOne Global Partners, Chicago, IL, USA)—whose composition and characterization are scarcely available in the scientific literature [ 38 ].…”

Section: Application Of Sedds In Brain Drug Delivery—pre-clinical Stu...mentioning

confidence: 99%

See 4 more Smart Citations

Self-Emulsifying Drug Delivery Systems: An Alternative Approach to Improve Brain Bioavailability of Poorly Water-Soluble Drugs through Intranasal Administration

2022

View full text Add to dashboard Cite

Efforts in discovering new and effective neurotherapeutics are made daily, although most fail to reach clinical trials. The main reason is their poor bioavailability, related to poor aqueous solubility, limited permeability through biological membranes, and the hepatic first-pass metabolism. Nevertheless, crossing the blood–brain barrier is the major drawback associated with brain drug delivery. To overcome it, intranasal administration has become more attractive, in some cases even surpassing the oral route. The unique anatomical features of the nasal cavity allow partial direct drug delivery to the brain, circumventing the blood–brain barrier. Systemic absorption through the nasal cavity also avoids the hepatic first-pass metabolism, increasing the systemic bioavailability of highly metabolized entities. Nevertheless, most neurotherapeutics present physicochemical characteristics that require them to be formulated in lipidic nanosystems as self-emulsifying drug delivery systems (SEDDS). These are isotropic mixtures of oils, surfactants, and co-surfactants that, after aqueous dilution, generate micro or nanoemulsions loading high concentrations of lipophilic drugs. SEDDS should overcome drug precipitation in absorption sites, increase their permeation through absorptive membranes, and enhance the stability of labile drugs against enzymatic activity. Thus, combining the advantages of SEDDS and those of the intranasal route for brain delivery, an increase in drugs’ brain targeting and bioavailability could be expected. This review deeply characterizes SEDDS as a lipidic nanosystem, gathering important information regarding the mechanisms associated with the intranasal delivery of drugs loaded in SEDDS. In the end, in vivo results after SEDDS intranasal or oral administration are discussed, globally revealing their efficacy in comparison with common solutions or suspensions.

show abstract

Section: Sedds Development For Delivery Of Neurotherapeutics Agents T...mentioning

confidence: 89%

Section: Sedds Development For Delivery Of Neurotherapeutics Agents T...mentioning

confidence: 99%

Section: Application Of Sedds In Brain Drug Delivery—pre-clinical Stu...mentioning

confidence: 99%

Section: Application Of Sedds In Brain Drug Delivery—pre-clinical Stu...mentioning

confidence: 99%

Section: Application Of Sedds In Brain Drug Delivery—pre-clinical Stu...mentioning

confidence: 99%

See 3 more Smart Citations

Self-Emulsifying Drug Delivery Systems: An Alternative Approach to Improve Brain Bioavailability of Poorly Water-Soluble Drugs through Intranasal Administration

2022

View full text Add to dashboard Cite

show abstract

An Update on Stiripentol Mechanisms of Action: A Narrative Review

Bacq,

Depaulis,

Castagné

et al. 2024

Adv Ther

View full text Add to dashboard Cite

Stiripentol (Diacomit ® ) (STP) is an orally active antiseizure medication (ASM) indicated as adjunctive therapy, for the treatment of seizures associated with Dravet syndrome (DS), a severe form of childhood epilepsy, in conjunction with clobazam and, in some regions valproic acid. Since the discovery of STP, several mechanisms of action (MoA) have been described that may explain its specific effect on seizures associated with DS. STP is mainly considered as a potentiator of gamma-aminobutyric acid (GABA) neurotransmission: (i) via uptake blockade, (ii) inhibition of degradation, but also (iii) as a positive allosteric modulator of GABA A receptors, especially those containing α3 and δ subunits. Blockade of voltage-gated sodium and T-type calcium channels, which is classically associated with anticonvulsant and neuroprotective properties, has also been demonstrated for STP. Finally, several studies indicate that STP could regulate glucose energy metabolism and inhibit lactate dehydrogenase. STP is also an inhibitor of several cytochrome P450 enzymes involved in the metabolism of other ASMs, contributing to boost their anticonvulsant efficacy as add-on therapy. These different MoAs involved in treatment of DS and recent data suggest a potential for STP to treat other neurological or non-neurological diseases.

show abstract

Quality by design approach-based fabrication and evaluation of self-nanoemulsifying drug delivery system for improved delivery of venetoclax

Rajana,

Chary,

Pooja

et al. 2023

Drug Deliv. and Transl. Res.

View full text Add to dashboard Cite

Using Self-Nanoemulsifying System to Improve Oral Bioavailability of a Pediatric Antiepileptic Agent Stiripentol: Formulation and Pharmacokinetics Studies

Cited by 6 publications

References 40 publications

Self-Emulsifying Drug Delivery Systems: An Alternative Approach to Improve Brain Bioavailability of Poorly Water-Soluble Drugs through Intranasal Administration

Self-Emulsifying Drug Delivery Systems: An Alternative Approach to Improve Brain Bioavailability of Poorly Water-Soluble Drugs through Intranasal Administration

An Update on Stiripentol Mechanisms of Action: A Narrative Review

Quality by design approach-based fabrication and evaluation of self-nanoemulsifying drug delivery system for improved delivery of venetoclax

Contact Info

Product

Resources

About