Intranasal Clobazam Delivery in the Treatment of Status Epilepticus

Florence, Kiruba; Lalan, Manisha; Kumar, Babbar Anil; Kaul, Ankur; Kumar, Mishra Anil; Ambikanandan, Misra

doi:10.1002/jps.22307

Cited by 39 publications

(18 citation statements)

References 48 publications

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“…agents, which act by their interaction with the tight junctions in the mucosal membrane and help in improved adhesion of formulation with nasal mucosa; which result in increased retention time and hence increased diffusion. CH-ME showed higher diffusion coefficient compared to CTAB-ME indicating the higher penetration enhancing properties and improved mucoadhesion performance with CH (Illum, 1998;Florence et al, 2011) and was in the further agreement with the results obtained from viscosity, contact angle and ex-vivo mucoadhesion of ME and MMEs, wherein the formulation with highest viscosity, greater contact angle and highest mucoadhesion exhibited higher diffusion coefficient. From the values of regression coefficients, as shown in Table 5, which clearly showed that the CH-ME exhibited highest r 2 value (0.9773) for Higuchi model compared to zero-order and first-order indicating the partitioning through diffusion, since the goat mucosa acts as a barrier or controlling membrane; hence, the diffusion process will mimic and shall be closer to reservoir system than zero-order (concentration independent) or firstorder (concentration gradient) diffusion (Kumar et al, 2009).…”

Section: Characterization Parameterssupporting

confidence: 85%

“…Receptor compartment was filled with PBS (pH 6.4), and same procedure as described above for in-vitro drug diffusion study was followed to determine the amount of drug diffused across excised nasal mucosa using HPLC method. Study was performed in triplicate, and the mean values for percentage drug diffused versus time were plotted against time (h) individually for ME, MMEs, and DS (Florence et al, 2011). Amount of drug permeated/unit area of nasal mucosa (mg/ cm 2 ) versus time were plotted against time (h) for ME, MMEs and DS, and from the slope of individual plot, flux and diffusion coefficients were calculated (Jadhav et al, 2010).…”

Section: Characterizationmentioning

confidence: 99%

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Nose to brain microemulsion-based drug delivery system of rivastigmine: formulation and ex-vivo characterization

et al. 2014

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder leading to irreversible loss of neurons, cognition and formation of abnormal protein aggregates. Rivastigmine, a reversible cholinesterase inhibitor used for the treatment of AD, undergoes extensive first-pass metabolism, thus limiting its absolute bioavailability to only 36% after 3-mg dose. Due to extreme aqueous solubility, rivastigmine shows poor penetration and lesser concentration in the brain thus requiring frequent oral dosing. This investigation was aimed to formulate microemulsion (ME) and mucoadhesive microemulsions (MMEs) of rivastigmine for nose to brain delivery and to compare percentage drug diffused for both systems using in-vitro and ex-vivo study. Rivastigmine-loaded ME and MMEs were prepared by titration method and characterized for drug content, globule size distribution, zeta potential, pH, viscosity and nasal ciliotoxicity study. Rivastigmine-loaded ME system containing 8% w/w Capmul MCM EP, 44% w/w Labrasol:Transcutol-P (1:1) and 48% w/w distilled water was formulated, whereas 0.3% w/ w chitosan (CH) and cetyl trimethyl ammonium bromide (as mucoadhesive agents) were used to formulate MMEs, respectively. ME and MMEs formulations were transparent with drug content, globule size and zeta potential in the range of 98.59% to 99.43%, 53.8 nm to 55.4 nm and À2.73 mV to 6.52 mV, respectively. MME containing 0.3% w/w CH followed Higuchi model (r 2 ¼ 0.9773) and showed highest diffusion coefficient. It was free from nasal ciliotoxicity and stable for three months. However, the potential of developed CH-based MME for nose to brain delivery of rivastigmine can only be established after in-vivo and biodistribution study.

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Section: Characterization Parameterssupporting

confidence: 85%

Section: Characterizationmentioning

confidence: 99%

Nose to brain microemulsion-based drug delivery system of rivastigmine: formulation and ex-vivo characterization

et al. 2014

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“…The pharmacodynamics study was conducted according to the protocol described by Florence et al (2011). Male Swiss albino mice weighing from 25 to 35 g were allocated randomly to four different groups (n ¼ 60).…”

Section: Pharmacodynamics Studymentioning

confidence: 99%

“…The ability of the preparations to protect mice from PTZinduced seizures after intravenous and intranasal administrations was evaluated to compare the preparations and their delivery routes (Florence et al, 2011). PTZ was administered after predefined intervals of 15-, 30-, and 45-min posttreatment with CZ preparations.…”

Section: Pharmacodynamic Studiesmentioning

confidence: 99%

Intranasal brain-targeted clonazepam polymeric micelles for immediate control of status epilepticus: in vitro optimization, ex vivo determination of cytotoxicity, in vivo biodistribution and pharmacodynamics studies

et al. 2016

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Clonazepam (CZ) is an anti-epileptic drug used mainly in status epilepticus (SE). The drug belongs to Class II according to BCS classification with very limited solubility and high permeability and it suffers from extensive first-pass metabolism. The aim of the present study was to develop CZ-loaded polymeric micelles (PM) for direct brain delivery allowing immediate control of SE. PM were prepared via thin film hydration (TFH) technique adopting a central composite face-centered design (CCFD). The seventeen developed formulae were evaluated in terms of entrapment efficiency (EE), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and in vitro release. For evaluating the in vivo behavior of the optimized formula, both biodistrbution using 99m Tc-radiolabeled CZ and pharmacodynamics studies were done in addition to ex vivo cytotoxicty. At a drug:Pluronic Õ P123:Pluronic Õ L121 ratio of 1:20:20 (PM7), a high EE, ZP, Q8h, and a low PDI was achieved. The biodistribution studies revealed that the optimized formula had significantly higher drug targeting efficiency (DTE ¼ 242.3%), drug targeting index (DTI ¼ 144.25), and nose-to-brain direct transport percentage (DTP ¼ 99.30%) and a significant prolongation of protection from seizures in comparison to the intranasally administered solution with minor histopathological changes. The declared results reveal the ability of the developed PM to be a strong potential candidate for the emergency treatment of SE.

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“…Recently, several nasal formulations, such as ergotamine (Novartis), sumatriptan (GlaxoSmithKline), and zolmitriptan (AstraZeneca) have been marketed to treat migraine. Scientists have also focused their research toward intranasal administration for drug delivery to the brain especially for the treatment of diseases, such as epilepsy [2][3][4][5][6][7] , migraine [8][9][10][11][12][13] , emesis, depression Even though the drugs used for the treatment of CNS disorders are potent, their clinical failure is often not due to lack of drug efficacy but mainly due to short comings in the drug delivery approach. Hence, scientists are exploring the novel approaches so that delivery of the drugs can be enhanced and /or restricted to the brain and CNS.…”

Section: Introductionmentioning

confidence: 99%

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2013

IJPSR

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Nasal route is found to be valuable for targeting drugs to CNS via different mechanisms. The advantages, disadvantages, varius aspects of nasal anatomy and physiology, mechanism of drug transport from nose brain, drug selection criteria to cross BBB/Blood-CSF barrier are discussed briefly. The relevant aspects of physicochemical, formulation and physiological factors of nasal cavity that must be considered during the process of discovery and development of new drugs for nasal delivery drugs as well as in their incorporation into appropriate nasal pharmaceutical formulations are discussed here. There are various approaches in delivering a therapeutic substance to the target site in a controlled release fashion. One such approach is using microemulsion as carriers for drugs. Microemulsions are isotropic, thermodynamically stable transparent (or translucent) systems of oil, water and surfactant, frequently in combination with a cosurfactant with a droplet size usually in the range of 10-100 nm. They can be classified as oil-in-water (o/w), water-in-oil (w/o) or bicontinuous systems depending on their structure and are characterized by ultra-low interfacial tension between oil and water phases. Microemulsion received much attention not only for prolonged release, but also for targeting of drugs to a particular site. The intent of the paper is focuses on use of microemulsion technology in drug targeting to the brain along with mechanism of nose to brain transport, formulation and formation of microemulsion and its characterization. INTRODUCTION:

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Intranasal Clobazam Delivery in the Treatment of Status Epilepticus

Cited by 39 publications

References 48 publications

Nose to brain microemulsion-based drug delivery system of rivastigmine: formulation and ex-vivo characterization

Nose to brain microemulsion-based drug delivery system of rivastigmine: formulation and ex-vivo characterization

Intranasal brain-targeted clonazepam polymeric micelles for immediate control of status epilepticus: in vitro optimization, ex vivo determination of cytotoxicity, in vivo biodistribution and pharmacodynamics studies

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