Intranasal delivery of antiseizure drugs

Pires, Patrícia C.; Melo, Dora Fátima Neves de; Santos, Adriana O.

doi:10.1016/b978-0-12-819838-4.00022-5

Cited by 4 publications

(8 citation statements)

References 69 publications

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“…In addition, a combination of these strategies can also be employed. Nanometric emulsions 3 Curcumin 0.006 5 [23] Polymer-coated nanometric emulsions 4 Curcumin 0.006 1.9 [24] Drug molecule modification Salts and hydrophilic prodrugs Phenytoin (used as fosphenytoin) 0.07 34.8 (equivalent to 50 mg/mL fosphenytoin) [25] Diazepam (avizafone) 0.05…”

Section: Overview Of Intranasal Formulation Strategies For Drugs With...mentioning

confidence: 99%

“…Hence, in intravenous administration simple acidified saline solutions (pH 3–4) are used, since midazolam converts to its water-soluble form at this pH [ 39 ]. However, lacrimation, throat, and nose burning, and general discomfort are associated with the intranasal administration of these same preparations, which shows that albeit effective, there was still room for improvement regarding formulation safety [ 4 , 40 ].…”

Section: Use Of Excipients For Enhanced Aqueous Solubilitymentioning

confidence: 99%

“…As previously mentioned, intranasal benzodiazepines have shown to be at least as effective in stopping seizures and preventing their recurrence as intravenous, intramuscular, rectal, or buccal administrations of the same drugs [ 34 , 35 , 36 , 37 ]. Several clinical trials with intranasal administration of benzodiazepines have been undertaken, either using parenteral solutions employing cosolvents, or alternative formulations, including using a liquid surfactant as solvent (Polyoxyl 35 castor oil or Cremophor ® EL, nowadays brand name Kolliphor ® EL) (reviewed by Pires et al [ 4 ]). Midazolam and diazepam innovative formulations have since reached the market.…”

Section: Use Of Excipients For Enhanced Aqueous Solubilitymentioning

confidence: 99%

“…Hence, drug solubilization was in both cases performed by adding high amounts of organic cosolvents and/or surfactants to the preparations. Nevertheless, organic solvents have been associated with reports of lacrimation, alteration in taste sensation, rhinorrhea, and burning and general discomfort in the nose and upper respiratory tract to different extents, depending on the exact excipients and their dose [ 4 , 40 , 49 , 50 , 51 , 52 , 53 ]. Despite favorable results regarding the approved midazolam and diazepam intranasal formulations, there seems to be scope for improvement regarding formulation tolerability.…”

Section: Use Of Excipients For Enhanced Aqueous Solubilitymentioning

confidence: 99%

“…One of these advantages is its non-invasiveness and ease of administration, hence not requiring trained professionals or in-hospital setting. This feature, together with potentially fast absorption and onset of action, makes intranasal delivery favorable for the management of certain emergency situations such as acute seizure episodes or opioid overdose [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

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Strategies to Improve Drug Strength in Nasal Preparations for Brain Delivery of Low Aqueous Solubility Drugs

et al. 2022

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Intranasal administration is a promising route for brain drug delivery. However, it can be difficult to formulate drugs that have low water solubility into high strength intranasal solutions. Hence, the purpose of this work was to review the strategies that have been used to increase drug strength in intranasal liquid formulations. Three main groups of strategies are: the use of solubilizers (change in pH, complexation and the use cosolvents/surfactants); incorporation of the drugs into a carrier nanosystem; modifications of the molecules themselves (use of salts or hydrophilic prodrugs). The use of high amounts of cosolvents and/or surfactants and pH decrease below 4 usually lead to local adverse effects, such as nasal and upper respiratory tract irritation. Cyclodextrins and (many) different carrier nanosystems, on the other hand, could be safer for intranasal administration at reasonably high concentrations, depending on selected excipients and their dose. While added attributes such as enhanced permeation, sustained delivery, or increased direct brain transport could be achieved, a great effort of optimization will be required. On the other hand, hydrophilic prodrugs, whether co-administered with a converting enzyme or not, can be used at very high concentrations, and have resulted in a fast prodrug to parent drug conversion and led to high brain drug levels. Nevertheless, the choice of which strategy to use will always depend on the characteristics of the drug and must be a case-by-case approach.

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Section: Overview Of Intranasal Formulation Strategies For Drugs With...mentioning

confidence: 99%

Section: Use Of Excipients For Enhanced Aqueous Solubilitymentioning

confidence: 99%

Section: Use Of Excipients For Enhanced Aqueous Solubilitymentioning

confidence: 99%

Section: Use Of Excipients For Enhanced Aqueous Solubilitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Strategies to Improve Drug Strength in Nasal Preparations for Brain Delivery of Low Aqueous Solubility Drugs

et al. 2022

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Antipsychotics-Loaded Nanometric Emulsions for Brain Delivery

2022

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Antipsychotic drugs have numerous disabling side effects, and many are lipophilic, making them hard to formulate at high strength. Incorporating them into nanometric emulsions can increase their solubility, protect them from degradation, and increase their brain delivery, being a promising strategy to overcome the current treatment gap. A thorough review was performed to assess the true potential of these formulations for antipsychotic drugs brain delivery. Intranasal administration was preferred when compared to oral or intravenous administration, since it allowed for direct brain drug transport and reduced systemic drug distribution, having increased efficacy and safety. Moreover, the developed systems increased antipsychotic drug solubility up to 4796 times (when compared to water), which is quite substantial. In the in vivo experiments, nanometric emulsions performed better than drug solutions or suspensions, leading to improved brain drug targeting, mainly due to these formulation’s excipients (surfactants and cosolvents) permeation enhancing capability, added to a small droplet size, which leaves a large surface area available for drug absorption to occur. Thus, even if it is difficult to conclude on which formulation composition leads to a best performance (high number of variables), overall nanometric emulsions have proven to be promising strategies to improve brain bioavailability of antipsychotic drugs.

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Nano and Microemulsions for the Treatment of Depressive and Anxiety Disorders: An Efficient Approach to Improve Solubility, Brain Bioavailability and Therapeutic Efficacy

2022

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Most drugs used for the treatment of depression, anxiety and related disorders have low absorption, high metabolism, low brain targeting and/or low water solubility, which can make it hard to formulate them at high strength and can also lead to decreased bioavailability. Incorporating these drugs into nanometric emulsions can solve these issues. Hence, the aim of the present review was to assess the potential of nano and micro emulsions for the delivery of antidepressant and anxiolytic drugs. The results from several studies showed that nanometric emulsions were able to increase drug strength up to 20,270-fold (compared to aqueous solubility). Moreover, in general, the formulations showed droplet size, polydispersity index, zeta potential, viscosity, osmolality, pH, in vitro drug release and ex vivo drug permeation as adequate for the intended effect and administration route. In vivo animal pharmacokinetic experiments showed that nanometric emulsions improved systemic drug bioavailability and/or brain targeting, and in vivo pharmacodynamic studies showed that they had antidepressant and/or anxiolytic effects, also being apparently safe. Hence, the current review provides proof of the potential of nano and microemulsions for improving solubilization and increasing the overall bioavailability of antidepressant and/or anxiolytic drugs, providing evidence of a possible useful strategy for future therapies.

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Intranasal delivery of antiseizure drugs

Cited by 4 publications

References 69 publications

Strategies to Improve Drug Strength in Nasal Preparations for Brain Delivery of Low Aqueous Solubility Drugs

Strategies to Improve Drug Strength in Nasal Preparations for Brain Delivery of Low Aqueous Solubility Drugs

Antipsychotics-Loaded Nanometric Emulsions for Brain Delivery

Nano and Microemulsions for the Treatment of Depressive and Anxiety Disorders: An Efficient Approach to Improve Solubility, Brain Bioavailability and Therapeutic Efficacy

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