Tags

Type your tag names separated by a space and hit enter

Nanoemulsions and thermosensitive nanoemulgels of phenytoin and fosphenytoin for intranasal administration: Formulation development and in vitro characterization.
Eur J Pharm Sci 2020; 141:105099EJ

Abstract

Phenytoin is a low solubility anticonvulsant drug. It has, nonetheless, other possible therapeutic indications, such as neuropathic pain, including trigeminal neuralgia, or wound healing. Its use has decreased due to side effects, but nasal/intranasal administration could significantly increase drug safety and efficacy. The aim of this work was to develop and study nanoemulsions and thermosensitive nanoemulgels of phenytoin and fosphenytoin, in combination, for intranasal administration, with immediate and sustained release profiles. Nanoemulsions were prepared by adding the aqueous phase, containing gelling polymers in the case of nanoemulgels, to emulsion preconcentrates, followed, in the optimized procedure, by premix membrane emulsification. Formulation design and optimization was guided by drug strength, rheological behavior, osmolality, mean droplet size and polydispersity. Fosphenytoin interfered significantly with Carbopol but not with Pluronic's gelation, and allowed to achieve drug strengths equivalent to 22 or 27 mg/g of phenytoin in lead nanoemulsions, and 16.7 mg/g of phenytoin in the lead nanoemulgel. The final selected low viscosity nanoemulsions had an immediate or prolonged fosphenytoin release profile, depending of anhydrous phase proportion (10% or 40%, respectively). The thermosensitive nanoemulgel, with 10% anhydrous phase, showed prolonged drug release. Future studies will establish whether they are more suited for topical effects or therapeutic brain delivery.

Authors+Show Affiliations

Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal; Faculty of Health Sciences, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal. Electronic address: patriciapires93@gmail.com.Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal; Faculty of Health Sciences, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal. Electronic address: peixoto.dianarita@gmail.com.Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal; Faculty of Health Sciences, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal. Electronic address: isauraatexeira@hotmail.com.Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal; Faculty of Health Sciences, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal; Research Unit for Inland Development (UDI-IPG), Polytechnic Institute of Guarda, 6300-749 Guarda, Portugal. Electronic address: marciorodrigues@fcsaude.ubi.pt.Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal; Faculty of Health Sciences, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal. Electronic address: gilberto@fcsaude.ubi.pt.Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal; Faculty of Health Sciences, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal. Electronic address: asantos@fcsaude.ubi.pt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31672614

Citation

Pires, Patrícia C., et al. "Nanoemulsions and Thermosensitive Nanoemulgels of Phenytoin and Fosphenytoin for Intranasal Administration: Formulation Development and in Vitro Characterization." European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, vol. 141, 2020, p. 105099.
Pires PC, Peixoto D, Teixeira I, et al. Nanoemulsions and thermosensitive nanoemulgels of phenytoin and fosphenytoin for intranasal administration: Formulation development and in vitro characterization. Eur J Pharm Sci. 2020;141:105099.
Pires, P. C., Peixoto, D., Teixeira, I., Rodrigues, M., Alves, G., & Santos, A. O. (2020). Nanoemulsions and thermosensitive nanoemulgels of phenytoin and fosphenytoin for intranasal administration: Formulation development and in vitro characterization. European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, 141, p. 105099. doi:10.1016/j.ejps.2019.105099.
Pires PC, et al. Nanoemulsions and Thermosensitive Nanoemulgels of Phenytoin and Fosphenytoin for Intranasal Administration: Formulation Development and in Vitro Characterization. Eur J Pharm Sci. 2020 Jan 1;141:105099. PubMed PMID: 31672614.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nanoemulsions and thermosensitive nanoemulgels of phenytoin and fosphenytoin for intranasal administration: Formulation development and in vitro characterization. AU - Pires,Patrícia C, AU - Peixoto,Diana, AU - Teixeira,Isaura, AU - Rodrigues,Márcio, AU - Alves,Gilberto, AU - Santos,Adriana O, Y1 - 2019/10/28/ PY - 2019/07/15/received PY - 2019/09/10/revised PY - 2019/10/01/accepted PY - 2019/11/2/pubmed PY - 2019/11/2/medline PY - 2019/11/2/entrez KW - Fosphenytoin KW - Intranasal KW - Nanoemulgel KW - Nanoemulsion KW - Phenytoin KW - Premix membrane emulsification SP - 105099 EP - 105099 JF - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences JO - Eur J Pharm Sci VL - 141 N2 - Phenytoin is a low solubility anticonvulsant drug. It has, nonetheless, other possible therapeutic indications, such as neuropathic pain, including trigeminal neuralgia, or wound healing. Its use has decreased due to side effects, but nasal/intranasal administration could significantly increase drug safety and efficacy. The aim of this work was to develop and study nanoemulsions and thermosensitive nanoemulgels of phenytoin and fosphenytoin, in combination, for intranasal administration, with immediate and sustained release profiles. Nanoemulsions were prepared by adding the aqueous phase, containing gelling polymers in the case of nanoemulgels, to emulsion preconcentrates, followed, in the optimized procedure, by premix membrane emulsification. Formulation design and optimization was guided by drug strength, rheological behavior, osmolality, mean droplet size and polydispersity. Fosphenytoin interfered significantly with Carbopol but not with Pluronic's gelation, and allowed to achieve drug strengths equivalent to 22 or 27 mg/g of phenytoin in lead nanoemulsions, and 16.7 mg/g of phenytoin in the lead nanoemulgel. The final selected low viscosity nanoemulsions had an immediate or prolonged fosphenytoin release profile, depending of anhydrous phase proportion (10% or 40%, respectively). The thermosensitive nanoemulgel, with 10% anhydrous phase, showed prolonged drug release. Future studies will establish whether they are more suited for topical effects or therapeutic brain delivery. SN - 1879-0720 UR - https://www.unboundmedicine.com/medline/citation/31672614/Nanoemulsions_and_thermosensitive_nanoemulgels_of_phenytoin_and_fosphenytoin_for_intranasal_administration:_Formulation_development_and_in_vitro_characterization L2 - https://linkinghub.elsevier.com/retrieve/pii/S0928-0987(19)30372-0 DB - PRIME DP - Unbound Medicine ER -