scholarly journals DEVELOPMENT OF FROVATRIPTAN SUCCINATE MICROEMULSION FOR NASAL DELIVERY: OPTIMIZATION, IN VITRO AND IN VIVO EVALUATION

2019 ◽  
pp. 292-300 ◽  
Author(s):  
UPENDRA C GALGATTE ◽  
PRAVIN D CHAUDHARI
Keyword(s):  
Nasal Mucosa ◽  
Structural Changes ◽  
Research Work ◽  
Nasal Delivery ◽  
Nasal Administration ◽  
Pharmacokinetic Parameters ◽  
Albino Rats ◽  
In Vitro Tests ◽  
Lattice Design

Objective: The main objective of the present research work was to develop, optimize, and characterize microemulsion (ME) of frovatriptan succinate to improve brain transport. Methods: The pseudoternary phase diagrams were constructed for ME formulations composed of Capmul MCM, Cremophor EL, and propylene glycol. Frovatriptan succinate-loaded ME was optimized by simplex lattice design having the concentration of oil, surfactant, and cosurfactant representing three apex points on the triangle. These were taken as independent variables and percentage drug release as a response variable. All developed batches of ME were characterized for in vitro tests, histopathology study, and pharmacokinetics in Swiss albino rats. Results: Clear MEs were obtained. F5 having particle size – 142.0 nm, zeta potential – 17.7–−7.8 mv, refractive index – 1.38±0.20, drug content – 98.24±0.20%, and drug diffused through dialysis membrane – 85% was the optimized batch. Drug permeation through the nasal mucosa of F5 in the ex vivo study was found to be 82.32%. Histopathology microscopic study has shown that F5 does not cause any irritation and structural changes in sheep nasal mucosa. The pharmacokinetic parameters were determined after nasal and oral administration of F5. For brain tissue, after nasal administration were Cmax181±1.51 ng/ml, Tmax – 2±1.01, area under curve (AUC)0−6 – 390.0±2.08 ng.h/ml. The AUC0−6 attained by nasal ME was 3.29 times greater than oral solution. Drug targeting index of frovatriptan succinate was 2.06. This was found satisfactory. Conclusion: Microemulsion of said composition was found to be enhancing delivery of frovatriptan succinate to brain tissues through nasal route.

scholarly journals Preparation, characterization, and in vivo pharmacokinetics of thermosensitive in situ nasal gel of donepezil hydrochloride

2020 ◽  
Vol 70 (3) ◽  
pp. 411-422 ◽  
Author(s):  
Fugen Gu ◽  
Huimin Fan ◽  
Zhixin Cong ◽  
Shuang Li ◽  
Yi Wang ◽  
...  
Keyword(s):  
Ph Value ◽  
Relative Bioavailability ◽  
Nasal Delivery ◽  
Poloxamer 407 ◽  
Nasal Administration ◽  
Pharmacokinetic Parameters ◽  
Donepezil Hydrochloride

AbstractDonepezil hydrochloride thermosensitive in situ gel for nasal delivery was prepared by using Poloxamer 407 and Poloxamer 188 as thermoreversible polymers, hydroxypropyl-β-cyclodextrin and ethylparaben as permeation enhancer and preservative, respectively. The gelation temperature and time, pH value of the gel formulation were found to meet the requirements for nasal administration. The in vitro erosion and in vitro release tests exhibited obvious drug sustained release behavior. Meantime, main pharmacokinetic parameters such as tmax, cmax and AUC in plasma as well as in brain were significantly different between the nasal gel formulation and intragastric drug solution in rats (p < 0.01). The relative bioavailability and drug targeting efficiency of the gel formulation were calculated to be 385.6 and 151.2 %, respectively. Thus, the drug gel formulation might be a potential new delivery system for treatment of Alzheimer’s disease due to its higher bioavailability and better distribution to brain when compared to oral route.

scholarly journals Search and evaluation of pharmacodynamic and pharmacokinetic parameters of selective blocker of TRPA 1 ion channels from the group of substituted pyrazinopyrimidinones

2018 ◽  
Vol 4 (3) ◽  
pp. 49-62
Author(s):  
Evgeniya А. Beskhmelnitsyna ◽  
Dmitriy V. Kravchenko ◽  
Lev N. Sernov ◽  
Irina N. Dolzhikova ◽  
Tatyana V. Avtina ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Laboratory Animals ◽  
Absolute Bioavailability ◽  
Organ Distribution ◽  
Pharmacokinetic Parameters ◽  
In Vitro Tests ◽  
Activity Levels ◽  
General Locomotor Activity ◽  
Anti Inflammatory

Introduction. Doctors of almost all specialties have to deal with the problem of pain and its relief. According to the literature, almost 30 million people daily take analgesics from the group of non-opioid analgesics, but in more than half of them 4-6 hours after taking the medication, the severity of pain is unchanged. Objective. to search for the most active molecules potential selective inhibitors of the TRPA1 ion channel with further investigation of their pharmacodynamic effects, toxicological safety, pharmacokinetic parameters and organ distribution, as well as to assess their impact on the psychoemotional state, general locomotor activity levels and anxiety in laboratory animals. Materials and methods. According to the results of in vitro tests, the most active molecule under code ZC02-0012 was selected from the pool of candidates. Further its analgesic activity was evaluated using an acetic acid-induced writhing test and a hot plate test; its anti-inflammatory activity was studied in the acute exudative paw edema model; in the open field and elevated plus-maze tests the influence of ZC02-0012 on the general locomotor activity levels and the anxiety of the laboratory animals was studied. The pharmacokinetic parameters and organ distribution of the substance ZC02-0012 were studied using a liquid chromatograph with an operating pressure range of 0-60 mPa (Thermo Scientific Dionex UltiMate 3000). Results and discussion. According to the results of in vitro tests, it was found that IC50 of the TRPA1 selective inhibitor under laboratory code ZC02-0012 was 91.3 nmol. The preclinical studies showed that ZC02-0012 possessed pronounced analgesic and anti-inflammatory activities and absence of the influence on the behavior and anxiety of the laboratory animals. Absolute bioavailability of ZC02-0012 in rabbits was 47%, while ZC02-0012 was intensely distributed into organs and tissues with a high level of blood circulation. The highest content of ZC02-0012 is typical of liver, kidneys and lungs, the lowest – for muscle tissue. Most of the substance is undergone rapid biotransformation and excreted as metabolites.

FORMULATION AND IN-VITRO EVALUATION OF ZOLMITRIPTAN IN SITU GEL FOR NASAL ADMINISTRATION

INDIAN DRUGS ◽  
2013 ◽  
Vol 50 (12) ◽  
pp. 54-58
Author(s):  
P. H Patil ◽  
◽  
V. S Belgamwar ◽  
D. A Patel ◽  
S. J. Surana
Keyword(s):  
Evaluation Studies ◽  
Methyl Cellulose ◽  
Nasal Delivery ◽  
Nasal Administration ◽  
Histopathological Study ◽  
In Situ Gel ◽  
In Vitro Evaluation ◽  
Effective Delivery

The aim of present investigation was formulation and in-vitro evaluation of in situ gel for the nasal delivery of zolmitriptan. The in situ gel was prepared by temperature induced gelation technique using Pluronic with mucoadhesive polymer hydroxy propyl methyl cellulose K4 M in different ratios. The in situ gels so prepared were characterized and from the evaluation studies, batch PH2 was optimized and further subjected for stability studies at 30±2°C and 60±5% RH for 90 days. These formulations retained good stability at accelerated conditions and also did not show any remarkable damage to nasal mucosa in histopathological study. Owing to these properties it can be used as an effective delivery system for the nasal route.

scholarly journals Bioaccessibility and Pharmacokinetics of a Commercial Saffron (Crocus sativus L.) Extract

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Paula Almodóvar ◽  
David Briskey ◽  
Amanda Rao ◽  
Marín Prodanov ◽  
Antonio M. Inarejos-García
Keyword(s):  
Research Work ◽  
Crocus Sativus ◽  
Pharmacokinetic Parameters ◽  
Healthy Human ◽  
Digestion Process ◽  
Oral Consumption ◽  
Quantification Analysis ◽  
Saffron Extract ◽  
Galenic Form

There are few studies about the pharmacokinetics of the low-molecular mass carotenoids crocetin or crocin isomers from saffron (Crocus sativus L.). None has been performed with a galenic preparation of a standardised saffron extract. The aim of the present research work was to study the effect of in vitro digestion process on the main bioactive components of saffron extract tablets and the corresponding pharmacokinetic parameters in humans. Pharmacokinetics were calculated collecting blood samples every 30 min during the first 3 h and at 24 h after administration of two different concentrations (56 and 84 mg of the saffron extract) to 13 healthy human volunteers. Additionally, an in vitro digestion process was performed in order to determine the bioaccessibility of saffron main bioactive compounds. Identification and quantification analysis were performed by HPLC-PAD/MS. Digestion resulted in 40% of bioaccesibility for crocin isomers, whereas, safranal content followed an opposite trend increasing about 2 folds its initial concentration after the digestion process. Crocetin in plasma was detected in a maximum concentration (Cmax) in blood between 60 and 90 min after oral consumption with dose-dependent response kinetics, showing that crocin isomers from galenic preparation of saffron extract are rapidly transformed into crocetin. The results showed that this tested galenic form is an efficient way to administer a saffron extract, since the observed crocetin Cmax was similar and more quickly bioavailable than those obtained by other studies with much higher concentrations of crocetin.

scholarly journals Antioxidant and Hepatoprotective Potentials of Lasimorpha senegalensis Schott Leaf Extract on Carbon Tetrachloride-induced Liver Damage in Rats

2020 ◽  
pp. 70-78
Author(s):  
Chinyere Blessing Chigor ◽  
Felix Ifeanyi Nwafor ◽  
Edith Ugwuja ◽  
Chisimdi S. Obi
Keyword(s):  
Liver Damage ◽  
Leaf Extract ◽  
Liver Enzymes ◽  
Radical Scavenging Activity ◽  
Research Work ◽  
Radical Scavenging ◽  
Albino Rats ◽  
Endogenous Antioxidants ◽  
Wistar Albino Rats

Aims: The present study assessed the antioxidant and hepatoprotective potentials of the methanolic leaf extract of Lasimorpha senegalensis – a medicinal plant used by the indigenous people of Nigeria to treat hepatitis and feverish conditions. Place and Duration of Study: The research work was conducted in the Department of Pharmacognosy and Environmental Medicine and Department of Plant Science and Biotechnology, both in the University of Nigeria, Nsukka, from May to August, 2019. Methodology: Phytochemical analyses and acute toxicity study of the sample followed standard procedures. In vitro antioxidant assay was by DPPH and H2O2 models. A total of 25 male Wistar albino rats (120 – 150 g) were grouped into five, each group with five animals. Hepatotoxicity was induced with carbontetrachloride (1 ml/kg). The treatment groups (3-5) received extract (200 and 400 mg/kg) and Silymarin (100 mg/kg). Endogenous antioxidants (superoxide dismutase, catalase, glutathione peroxidase), plasma malondialdehyde and liver enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphate) were determined after treatment. Results: The results showed the leaf extract had appreciable amounts of bioactive phytochemicals and free radical scavenging activity (IC50 of 0.52 mg/ml and 0.71 mg/ml for DPPH and H2O2 respectively) with no toxicity at 5000 mg/kg. The extract also elevated the endogenous antioxidants and significantly (p ≤ .05) reduced lipid peroxidase and liver enzymes. Conclusion: This report justifies the local use of this plant in the management of various diseases related to oxidative stress and liver damage.

scholarly journals Selective targeting of the TLR2/MyD88/NF-κB pathway reduces α-synuclein spreading in vitro and in vivo

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Debashis Dutta ◽  
Malabendu Jana ◽  
Moumita Majumder ◽  
Susanta Mondal ◽  
Avik Roy ◽  
...  
Keyword(s):  
Lewy Bodies ◽  
Selective Inhibition ◽  
Nasal Delivery ◽  
Nasal Administration ◽  
Interaction Domain ◽  
Selective Targeting ◽  
Nemo Binding Domain ◽  
Microglial Inflammation

AbstractPathways to control the spreading of α-synuclein (α-syn) and associated neuropathology in Parkinson’s disease (PD), multiple system atrophy (MSA) and dementia with Lewy bodies (DLB) are unclear. Here, we show that preformed α-syn fibrils (PFF) increase the association between TLR2 and MyD88, resulting in microglial activation. The TLR2-interaction domain of MyD88 (wtTIDM) peptide-mediated selective inhibition of TLR2 reduces PFF-induced microglial inflammation in vitro. In PFF-seeded A53T mice, the nasal administration of the wtTIDM peptide, NEMO-binding domain (wtNBD) peptide, or genetic deletion of TLR2 reduces glial inflammation, decreases α-syn spreading, and protects dopaminergic neurons by inhibiting NF-κB. In summary, α-syn spreading depends on the TLR2/MyD88/NF-κB pathway and it can be reduced by nasal delivery of wtTIDM and wtNBD peptides.

In-Situ Gelling System based on Thiolated Gellan Gum as New Carrier for Nasal Administration of Dimenhydrinate

2009 ◽  
Vol 2 (2) ◽  
pp. 544-550
Author(s):  
Hitendra Mahajan ◽  
Hannan Shaikh ◽  
Surendra Gattani ◽  
Pankaj Nerkar
Keyword(s):  
Nasal Mucosa ◽  
Histopathological Examination ◽  
Polymer Concentration ◽  
Gellan Gum ◽  
Nasal Administration ◽  
In Vitro Permeation ◽  
Permeation Studies ◽  
In Situ Gelling

The purpose of the present study was to develop intranasal delivery system of dimenhydrinate using thiolated gellan gum and formulations were modulated so as to have gelation at physiological ion content after intranasal administration.  Gelation was determined by physical appearance.  The mucoadhesive force in terms of detachment stress, determined using sheep nasal mucosa, increased with increasing concentration of thiolated polymer. The results of in vitro drug permeation studies across sheep nasal mucosa indicate that effective permeation could be significantly increased by using in situ gelling formulation with thiolated polymer concentration.  Finally, histopathological examination did not detect any changes during in vitro permeation studies.  In conclusion the gel formulation of dimenhydrinate with in situ gelling and mucoadhesive properties with increased permeation rate is promising for prolonging nasal residence time and thereby nasal absorption.

scholarly journals DEVELOPMENT OF PARTICULATE MUCOADHESIVE GEL FOR INTRANASAL DELIVERY

2017 ◽  
Vol 10 (5) ◽  
pp. 222
Author(s):  
Dinanath Gaikwad ◽  
Padmini Kurane ◽  
Dipak Mali ◽  
Namdeo Jadhav
Keyword(s):  
Drug Release ◽  
Heart Diseases ◽  
Research Work ◽  
Entrapment Efficiency ◽  
Angle Of Repose ◽  
Nasal Administration ◽  
A Value ◽  
Compressibility Index ◽  
Zero Order Release

Objective: The objective of this research work was to develop mucoadhesive particulates gel of Propranolol HCl for intranasal delivery.Method: Drug loaded mucoadhesive particulates were prepared by spray drying technique using polymers such as HPMC K100 and Carbopol 934P. Batches were prepared according to 32 factorial designs.   Result: The mucoadhesive particulates prepared were evaluated for different parameters like drug content, entrapment efficiency, mucoadhesive strength and in vitro drug release. IR, XRD and DSC study revealed that there were no interaction occurs between drug and excipients and confirming reduction in crystallinity. The swelling index and encapsulation efficiency was found to be (0.9266%), (97.44%), angle of repose, Carr’s compressibility index falls in acceptable limits. At the end of 10 hr optimized batch showed 90.23 % drug release and followed zero order release kinetics.Conclusion: Conclusion from result of the studies such as increase in the concentration of polymers contributed in drug release retardation. Although, prepared formulation of nasal administration can be a value addition in treatment for heart diseases like angina pectoris, myocardialKeywords: Mucoadhesive, Particulates, Propranolol hydrochloride, Intranasal.infraction. 

scholarly journals DoE Directed Optimization, Development and Characterization of Resveratrol Loaded Nlc System for the Nose to Brain Delivery in the Management of Glioblastoma Multiforme

2021 ◽  
Author(s):  
Nitish Kumar ◽  
Ghanshyam Das Gupta ◽  
Daisy Arora
Keyword(s):  
Particle Size ◽  
Nasal Mucosa ◽  
Ex Vivo ◽  
Research Work ◽  
Spherical Shape ◽  
Entrapment Efficiency ◽  
Antioxidant Property ◽  
Brain Delivery ◽  
Antioxidant Assay

Abstract Nose to brain delivery of resveratrol can be a very useful method to overcome the limitations possessed by conventional delivery approaches namely, hepatic metabolism, low bioavailability and half-life of resveratrol, and presence of blood-brain barrier (BBB). The objective of this research work was to develop and optimize the resveratrol-loaded NLCs and coating these carriers with chitosan to increase the residence time of the formulation into the nasal cavity and enhanced permeation across the nasal mucosa. Three CQAs (Particle size, Entrapment efficiency, and PDI), and CMAs (Solid: total lipid concentration, surfactant concentration, and bioactive amount) were selected and the formulation was optimized using the Box-Behnken design (BBD) approach. The optimized batch was evaluated for physicochemical characteristics such as particle size (168.24 ± 8.24 nm), PDI (0.151 ± 0.003), and entrapment efficiency (77.42 ± 3.76 %). This optimized batch was coated with chitosan, which produced coated NLCs with a particle size of 317.7 ± 15.9 nm, and PDI was 0.089 ± 0.009. The morphological study using TEM confirmed the spherical shape, size, and surface coating of the NLCs. Furthermore, both the uncoated and coated particles were analyzed for in vitro resveratrol release, ex vivo diffusion study, and antioxidant assay. NLCs was founded to show sustained in vitro release characteristic, and enhanced bioactive diffusion across the nasal mucosa compared to the bioactive solution of resveratrol. The antioxidant assay revealed that the antioxidant property of resveratrol was intact in the formulation, and a slight increase in antioxidant activity of the formulation was also observed which may be due to the presence of sesame oil in the formulation. These results indicated that the chitosan-coated NLCs can be used to deliver therapeutic moieties more efficiently via the nose to brain drug delivery.

scholarly journals Preparation and in vivo evaluation of a gel-based nasal delivery system for risperidone

2016 ◽  
Vol 66 (4) ◽  
pp. 555-562 ◽  
Author(s):  
Fugen Gu ◽  
Weina Ma ◽  
Gendalai Meng ◽  
Chunzhi Wu ◽  
Yi Wang
Keyword(s):  
Relative Bioavailability ◽  
Nasal Delivery ◽  
Oral Drug ◽  
Pharmacokinetic Parameters ◽  
In Vivo Evaluation ◽  
Fast Absorption ◽  
Maximal Plasma ◽  
Vitro Effect

Abstract The aim of this study was to prepare a nasal gel of risperidone and to investigate the pharmacokinetics and relative bioavailability of the drug in rats. Compared with oral dosing, the risperidone nasal gel exhibited very fast absorption and high bioavailability. Maximal plasma concentration (cmax) and the time to reach cmax (tmax) were 15.2 μg mL-1 and 5 min for the nasal gel, 3.6 μg mL-1 and 30 min for the oral drug suspension, respectively. Pharmacokinetic parameters such as tmax′, cmax and AUC of oral and nasal routes were significantly different (p < 0.01). Relative bioavailability of the drug nasal preparation to the oral suspension was up to 1600.0 %. Further, the in vitro effect of the risperidone nasal gel on nasal mucociliary movement was also investigated using a toad palate model. The risperidone nasal formulation showed mild ciliotoxicity, but the adverse effect was temporary and reversible.

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