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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
Sat Nov 04 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences( P-issn 1683 - 3597 E-issn 2521 - 3512)
Study the Effect of Formulation Variables on Preparation of Nisoldipine Loaded Nano Bilosomes
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Nisoldipine (NSD) is a dihydropyridine class of calcium channel blockers used for hypertension treatment, it belongs to class II BCS (low solubility with high permeability), its absolute bioavailability is only 5% due to presystemic metabolism in the gut wall. It is also a substrate for a CYP3A and P-gp. Bilosomes are lipid bilayer vesicles incorporating bile salts in their walls to prevent degredation by GIT bile salts. The aim of this study is to prepare nisoldipine bilosomes as vesicular carrier and assess the effect of different formulation variables such as type of surfactant, amount of cholesterol, surfactant and sonication time on particle size, entrapment efficiency and poly dispersity index of the prepared bilos

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Publication Date
Sun Sep 01 2013
Journal Name
Baghdad Science Journal
Spectrophotometric Determination of Bismuth(III) with Arsenazo(III) Reagent in Water samples and Veterinary Preparation
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A simple , sensitive and accurate spectrophotometric method for the trace determination of bismuth (III) has been developed .This method is based on the reaction of bismuth (III) with arsenazo(III) in acid solution (pH=1.9) to form a blue water soluble complex which exhibits maximum absorption at 612nm .Beer's law is obeyed over the concentration range of 2-85 ?g bismuth (III) in a final volume of 20 mL( i.e. 0.1 – 4.25?g.mL-1) with a correlation coefficient of (0.9981) and molar absorptivity 1.9×104 L.mol-1.cm-1 . The limit of detection (LOD) and the limit of quantification (LOQ) are 0.0633 and 0.0847 ?g.mL-1 , respectively . Under optimum conditions,the stoichiometry of the reaction between bismuth (III) and arsenazo(III) r

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Publication Date
Sun Jun 21 2020
Journal Name
Baghdad Science Journal
Spectrophotometer Determination of Cefixime in pure form and pharmaceutical preparation by Using Cloud point Extraction
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Two simple methods spectrophotometric were suggested for the determination of Cefixime (CFX) in pure form and pharmaceutical preparation. The first method is based without cloud point (CPE) on diazotization of the Cefixime drug by sodium nitrite at 5Cº followed by coupling with ortho nitro phenol in basic medium to form orange colour. The product was stabilized and measured 400 nm. Beer’s law was obeyed in the concentration range of (10-160) μg∙mL-1 Sandell’s sensitivity was 0.0888μg∙cm-1, the detection limit was 0.07896μg∙mL-1, and the limit of Quantitation was 0.085389μg∙mL-1.The second method was cloud point extraction (CPE) with using  Trtion X-114 as surfactant. Beer

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Publication Date
Sun Feb 22 2026
Journal Name
Clinical Drug Investigation
A Field-Based Cost-Effectiveness Study of Aflibercept and Bevacizumab in Treat-and-Extend Versus Pro Re Nata Protocols for Diabetic Macular Edema in Iraq
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Sun Mar 01 2020
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مجلة العلوم النفسية
Emotional sensitivity in children from the parents' point of view Preparation
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The current research aims to: 1- Identify the emotional sensitivity of children from the parents' point of view. 2- Identifying the differences in the emotional sensitivity of children from the parents ’point of view, according to the parents’ gender variable (father - mother). The basic research sample consisted of (285) male and female students from the sixth grade (primary school), chosen in a randomized stratified method from the districts (Al-Karkh and AlRasafa). While the sample of statistical analysis amounted to (200) father and (200) mothers of male and female students who were randomly selected from the sixth grade of the education directorates (Al-Karkh and Al-Rasafa). The two researchers also used a number of sta

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Publication Date
Thu Nov 02 2023
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Al-rafidain Journal Of Medical Sciences ( Issn 2789-3219 )
Appraising the Role of Pharmacists in Medication Reconciliation at Hospital Discharge: A Field-Based Study
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Objective: To measure the effect of the pharmacist-led medication reconciliation service before hospital discharge on preventing potential medication errors. Methods: This behavioral interventional study took place in a public teaching hospital in Iraq between December 2022 and January 2023. It included inpatients who were taking four or more medications upon discharge from the internal medicine ward and the cardiac care unit. The researcher provided the patients with a medication reconciliation form and reconciliation form (including medication regimen and pharmacist instructions) before discharging them home. Any discrepancies between the patients’ understanding and the actual medication recommendations prescribed by the physici

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Publication Date
Sat Oct 01 2022
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Digest Journal Of Nanomaterials And Biostructures
Preparation and study effect of vacuum annealing on structure and optical properties of AgCuInSe<inf>2</inf> thin film
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Publication Date
Sat Dec 31 2022
Journal Name
International Journal Of Dentistry
Bond Strength Survival of a Novel Calcium Phosphate-Enriched Orthodontic Self-Etching System after Various Ageing Protocols: An In Vitro Study
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Objective. This study aimed to evaluate the orthodontic bond strength and enamel-preserving ability of a hydroxyapatite nanoparticles-containingself-etch system following exposure to various ageing methods. Materials and Methods. Hydroxyapatite nanoparticles (nHAp) were incorporated into an orthodontic self-etch primer (SEP, Transbond™ plus) in three different concentrations (5%, 7%, and 9% wt) and tested versus the plain SEP (control) for shear bond strength (SBS), adhesive remnant index (ARI) scores, and enamel damage in range-finding experiments using premolar teeth. The best-performing formulation was further exposed to the following four artificial ageing methods: initial debonding, 24 h water storage, one-month water stora

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Publication Date
Wed May 01 2024
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Journal Of International Society Of Preventive And Community Dentistry
Effect of Incorporating Chitosan to Resin Modified Glass Ionomer Cement on Shear Bond Strength to Dentin (An In vitro Comparative Study)
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A<sc>bstract</sc> <sec> <title>Aim:

Resin-modified glass ionomer cement tends to shrink due to polymerization of the resin component. Additionally, they are more prone to syneresis and imbibition during the setting process. This in vitro study evaluates the impact of chitosan, a biopolymer that is, both biomaterial and biocompatible, on the strength of dentin bonding and compares it with ACTIVA Bio-ACTIVE Restorative. The present study was aimed to assess the impact of including chitosan into Fuji II on the shear bond strength between. the restoration material and tooth dentin,

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Publication Date
Wed Jul 01 2020
Journal Name
Iop Conference Series: Materials Science And Engineering
Automation in architecture and its effect on the regeneration of traditional buildings: Al-Shawi House as a case study
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Abstract<p>The increased applications of technology in the field of architecture, especially digital technology and aspects of automation, have made a major impact on various aspects of local architecture, especially the traditional ones. As these technologies have succeeded in integrating many technological applications in many traditional and heritage buildings and taking them to more complex uses. And included in it characteristics that were not contained, therefore the research problem was concentrated in the absence of a holistic view of the role of the aspects of automation as a technological and design effect and its mutual effects on traditional buildings (especially the traditional Bagh</p> ... Show More
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