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Preparation, <i>In-vitro, Ex-vivo</i>, and Pharmacokinetic Study of Lasmiditan as Intranasal Nanoemulsion-based <i>In Situ</i> Gel
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Background:

Lasmiditan (LAS) is a recently developed antimigraine drug and was approved in October, 2019 for the treatment of acute migraines; however, it suffers from low oral bioavailability, which is around 40%.

Objective:

This study aimed to improve the LAS bioavailability via formulation as nanoemulsionbased in situ gel (NEIG) given intranasally and then compare the traditional aqueous-LASsuspension (AQS) with the two successful intranasal prepared formulations (NEIG 2 and NEIG 5) in order to determine its relative bioavailability (F-relative) via using rabbits.

Method:

Two successfully prepared nanoemulsion (NE) formulas, a and b, were selected for the incorporation of different percentages of pH-sensitive in situ gelling polymer (Carbopol 934) to prepare NEIGs 1, 2, 3, 4, 5, and 6. The pH, gelation capacity, gel strength, and viscosity were predicted for the prepared NEIGs. The release (in vitro) and the nasal permeation (ex vivo) were determined for NEIG 2 and 5, and then both were subjected to pharmacokinetics in vivo studies. Eighteen male rabbits weighing 2.0 to 2.5 kg were employed in the parallel design study. The body surface area (BSA) normalization method was applied for LAS dose calculation. Serial blood samples were taken out and subjected to drug analysis using the HPLC method previously developed and validated by Kumar et al. Primary pharmacokinetics parameters, including maximum drug concentration in plasma (Cmax), time to reach C-max (T-max), and area under the concentration-time curve from time zero to affinity (AUCt0-∞) were calculated. Both NE (a and b), together with NEIG (2 and 5) formulas, were subjected to the stability study. Finally, a nasal ciliotoxicity study was carried out to evaluate the nasal toxicity of developed NEIGs 2 and 5.

Result:

The results showed that NEIGs 2 and 5 could be selected as the optimized NEIGs as both achieved 100% permeation within 20 min and then released within 25 and 35 min, respectively, thus achieving 3.3 folds with higher permeation percentages as compared to the AQS. Both NEIGs 2 and 5 exerted comparable release and permeation values as the corresponding NE a and b with more residence time in order to overcome the normal nasal physiological clearance. The values of C-max, Tmax, and AUC0- ∞ for NEIG 2 and NEIG 5 were 8066 ± 242 ng/ml, 0.75 ± 0.05 h, 19616.86 ± 589 ng. h/ml, and 7975.67 ± 239 ng/ml, 1.0 ± 0.05 h, 17912.36 ± 537 ng. h/ml, respectively, compared to the traditional AQS, which is equal to 4181.09 ± 125 ng/ml, 2 ± 0.2 h, and 8852.27 ± 266 ng. h/ml, respectively. It was discovered that NEIGs 2 and 5 had better intranasal delivery of LAS and could significantly (p < 0.05) achieve a higher value of permeability coefficient (3.3 folds) and 2.5 folds improvement in bioavailability when compared to AQS. The NE a, NE b, NEIG2, and NEIG5 formulations showed good stability at various temperatures. According to the nasal ciliotoxicity study, the nasal mucosal membrane, which was treated with NEIG 5, showed irritation with a bit of damage. However, damage was not observed when it was treated with NEIG 2, indicating the biocompatibility of the last one to be selected as the optimum formula.

Conclusion:

NEIG 2 and NEIG 5 are promising new intranasal formulas with a faster onset of action and greater bioavailability than the oral dosage form (AQS). Finally, the selected optimum gold formula that will be ready for further clinical study is NEIG 2.

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Publication Date
Mon Aug 03 2026
Journal Name
Journal Of Baghdad College Of Dentistry
A Comparison of the Effectiveness of Reciprocating System with Continuous Rotary Systems in Non-Surgical Endodontic Retreatment (An In vitro study)
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Background: Optimal root canal retreatment was required safe and efficient removal of filling material from root canal. The aim of this in vitro study was to compare the efficacy of reciprocating and continuous motion of four retreatment systems in removal of root canal filling material. Materials and Methods: Forty distal roots of the mandibular first molars teeth were used in this study, these roots were embedded in cold clear acrylic,roots were instrumented using crown down technique and rotary ProTaper systemize Sx to size F2 ,instrumentation were done with copiousirrigation of 2.5% sodium hypochlorite and 17% buffered solution of EDTA was used as final irrigant followed by distilledwater, roots were obturated with AH26 sealer and Prota

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Publication Date
Mon Sep 30 2024
Journal Name
South Eastern European Journal Of Public Health
Antimicrobial Efficacy of a Novel Herbal Endodontic Irrigant Against Enterococcus Faecalis in Root Canals of Permanent Teeth: An in Vitro Study
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Background: A successful endodontic treatment is aimed at the sterilization of the entire pulp space. The use of extracts from Rhamnus prinoides as a novel irrigating material for root canal has not been studied . Hence, the antimicrobial efficacy of the alcoholic extract of Rhamnus prinoides as an irrigation material against E. faecalis was evaluated in comparison with the 2.5% sodium hypochlorite (NaOCL) solution used for root canals of permanent teeth. Methods: A total of 30 single-rooted human permanent teeth were thoroughly cleaned, shaped, and disinfected. Then, each tooth was subjected to a two-week infection with Enterococcus faecalis at 37 °C . Afterward, the samples were divided into three groups (10 teeth per group): 0.9

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Publication Date
Tue Mar 01 2016
Journal Name
Journal Of Baghdad College Of Dentistry
A Comparison of the Effectiveness of Reciprocating System with Continuous Rotary Systems in Non-Surgical Endodontic Retreatment (An In vitro study)
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Background: Optimal root canal retreatment was required safe and efficient removal of filling material from root canal. The aim of this in vitro study was to compare the efficacy of reciprocating and continuous motion of four retreatment systems in removal of root canal filling material. Materials and Methods: Forty distal roots of the mandibular first molars teeth were used in this study, these roots were embedded in cold clear acrylic,roots were instrumented using crown down technique and rotary ProTaper systemize Sx to size F2 ,instrumentation were done with copiousirrigation of 2.5% sodium hypochlorite and 17% buffered solution of EDTA was used as final irrigant followed by distilledwater, roots were obturated with AH26 sealer and Prota

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Publication Date
Sat Jan 01 2022
Journal Name
Biomed Research International
Zerumbone‐Loaded Nanostructured Lipid Carrier Gel Enhances Wound Healing in Diabetic Rats
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This study investigated the healing effects of topical application of zerumbone, a well‐known anti‐inflammatory compounds loaded on nanostructured lipid carrier gel (Carbopol 940) (ZER‐NLCG) on excisional wounds in streptozotocin‐induced diabetic rats. Diabetic rats with inflicted superficial skin wound were topically treated with ZER‐NLCG, empty NLCG, and silver sulfadiazine cream (SSDC) once daily for 21 days. Wound tissue samples were analyzed for proinflammatory cytokines, namely, interleukin‐6 (IL‐6), interleukin‐1 β (IL‐1β), and tumor necrosis factor‐α (TNF‐α), hydroxyproline contents, catalase,

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Publication Date
Sat Jan 01 2022
Journal Name
Dental Hypotheses
Comparison of Microleakage of Composite and Glass Ionomer Restorations in Primary Molars Pretreated with Silver Diamine Fluoride at Two Time Intervals: An In Vitro study
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Publication Date
Sun Dec 06 2009
Journal Name
Baghdad Science Journal
The influence of He-Ne Laser (632.8 nm) on Candida albicans isolated from complete upper dentures: In vitro study
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The main objective of this study is to determine whether the use of He-Ne Laser (632.8 nm wavelength and power 0.5 mW) is an eligible and effective tool to kill or reduce the cell viability of Candida albicans isolated from complete upper dentures. Twenty one swabs were taken from the complete upper dentures. Only six swabs showed positive cultures for C. albicans. The isolate was divided into two groups, group I was not irradiated (control), and group II was irradiated by He-Ne Laser for different periods (10, 15, 20, and 30) min. After irradiation, the results showed a significant reduction in the viable cell count and colonies diameters especially at exposure periods 10 and 15 min. Although the low power He-Ne Laser was not eradicating t

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Publication Date
Tue Jun 16 2020
Journal Name
Baghdad Science Journal
Qualitative and Quantitative Evaluation of Active Constituents in Callus of Lavandula angustifolia plant in Vitro
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This study was conducted to describe a protocol for the callus establishing culture of Lavandula angustifolia plant and estimating their content of volatile oil. The quantity of volatile oil callus tissues was compared with that of leaves production. Callus was induced from leaf explants on Murashige and Skoog medium (MS) supplemented with Naphthalene acetic acid (NAA) and Benzyl adenine (BA) in different concentrations. Maximum callus fresh weight was obtained in the combination of 10 mg/L BA and 3 mg/L NAA which reached 18 g after four weeks. The results of this work showed that the  quantity of volatile oil from the highest fresh weight callus was 6 ml compared with quantity of 18g of leaves which gave 0.5 ml. Volatile o

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Publication Date
Thu Oct 01 2009
Journal Name
Iraqi Journal Of Physics
Preparation Cadmium Telluride Compound and Study Structural Properties of thermal evaporation thin films
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Polycrystalline ingots of cadmium telluride have been synthesized using the direct
reaction technique, by fusing initial component consisting from pure elements in
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been grown under temperature at (1070) oC for (16) hr. was used in this study, the phases
observed in growing CdTe compound depend on the temperature used during the growth
process. Crystallography studies to CdTe compound was determined by X-ray diffraction
technique, which it has zinc blend structure and cubic unit cell, which lattice constants is
a=6.478
oA

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Publication Date
Wed Jun 30 2021
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
PREPARATION OF POLYMERIC COMPOSITES FROM SATURATED POLYESTERS GLASS POWDER (FLOURSCENT) AND STUDY OF ITS MECHANICAL PROPERTIES: PREPARATION OF POLYMERIC COMPOSITES FROM SATURATED POLYESTERS GLASS POWDER (FLOURSCENT) AND STUDY OF ITS MECHANICAL PROPERTIES
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In this study, polymeric composites were prepared from unsaturated polyester as a base material with glass powder (fluorescent) in different weight ratios (4, 6, 8, 10,and 11%) as a support material and after comparison before and after reinforcement of the prepared composites, an increase was found. In the values ​​of mechanical properties (hardness, compressive strength), the shock resistance values ​​decreased, but an increase in temperature leads to an increase in the values ​​of shock resistance, as well as the values ​​of compressive strength And it reduces the hardness value.

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Publication Date
Tue Jun 02 2020
Journal Name
International Journal Of Pharmaceutical Research
Etodolac Topical Spray Films, Development, Characterization and In-Vitro Evaluation
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