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Formulation and In Vivo Evaluation of Ticagrelor-Loaded Spanlastic Nanovesicles to Enhance Intestinal Absorption
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Introduction:

Ticagrelor (TCG) is an effective P2Y12 receptor antagonist used to prevent atherothrombotic cardiovascular events; however, its poor solubility and limited permeability (BCS Class IV) restrict its oral bioavailability. Spanlastic Nanovesicles (SNVs), composed of nonionic surfactants and edge activators, offer a promising strategy to enhance drug solubility and permeability. This study aimed to develop and optimize TCG-loaded SNVs using the ethanol injection method, validate a sensitive HPLC method for TCG quantification, and evaluate the pharmacokinetic and antiplatelet performance of the optimized formulation in rats.

Method:

TCG-SNVs were prepared using the ethanol injection technique with a varying ratio of Span 60 and Tween 60. Formulations were characterized for Particle Size (PS), Polydispersity Index (PDI), and Encapsulation Efficiency (EE %). Morphology was examined by Transmission Electron Microscope (TEM). A reversed -phase HPLC method was validated for linearity, accuracy, precision, LOD, and LOQ. In vivo pharmacokinetic studies were conducted in Sprague-Dawley rats (10 mg /kg oral dose), and pharmacokinetic parameters (C max, Tmax, AUC, t 1/2) were determined. Inhibition of platelet aggregation was evaluated using a dual-channel aggregometer.

Results:

Among the tested formulations, SNV2 showed optimal characteristics with a particle size of 79.21 nm, PDI of 0.1213, and EE % of 86.87%. TEM confirmed spherical and uniformly distributed vesicles. The validated HPLC method demonstrated excellent linearity (100-800 ng/ml), high accuracy (mean recovery 99%), and acceptable precision (% RSD < 2%), with LOD and LOQ values of 8 ng/mL and 24.24 ng/mL in plasma, respectively. Pharmacokinetic analysis revealed significantly enhanced systemic exposure for SNV2 compared to the marketed product, with increased Cmax (9500 vs. 4500 ng/ml), AUC (115150 vs. 70107.5 ng/mL), reduced Tmax (4 vs. 8 hours), and a relative bioavailability improvement of 64.33%. Additionally, SNV2 demonstrated a greater reduction in ADP-induced platelet aggregation than the comparator formulation.

Discussion:

The improved pharmacokinetic and pharmacodynamic performance of SNV2 can be attributed to enhanced solubility, nanoscale size, high encapsulation efficiency, and improved intestinal permeability provided by the flexible spanlastic vesicles. The validated HPLC method ensures accurate and reliable quantification of TCG in plasma, supporting the robustness of the in vivo findings.

Conclusion:

TCG-loaded spanlastic nanovesicles prepared by the ethanol injection method significantly enhanced oral bioavailability and antiplatelet efficacy compared to the marketed formulation. The optimized SNV2 formulation represents a promising nanocarrier system for improving the therapeutic performance of ticagrelor and may offer potential clinical benefits in the management of cardiovascular diseases.

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Publication Date
Sat Jul 08 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Formulation Characterization and Evaluation of Meloxicam Nanoemulgel to be Used Topically
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Meloxicam is a non-steroidal anti-inflammatory drug. It is practically insoluble in water. It is associated with gastrointestinal side effects at high doses on long  term treatment. The aim of this investigation to formulate and evaluate gellified nanoemulsion of meloxicam as a topical dosage form to enhance meloxicam therapeutic activity and reduce systemic side effect.

The pseudo ternary phase diagrams were made, including  the oil mixture which is composed of almond oil and peppermint oil at a ratio (1:2), variable surfactant mixture (S mix) which are tween 80 and ethanol at ratios of (1:1, 2:1, 3:1, and 4:1) and double distilled water. Slow dripping of double distilled water to the combination  of the oil mixtu

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Publication Date
Fri Nov 03 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences( P-issn 1683 - 3597 E-issn 2521 - 3512)
Diacerein Loaded Novasome for Transdermal Delivery: Prepartion , In-Vitro Characterization and Factors Affecting Formulation
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Diacerein (DCN) is a semi-synthetic anthraquinone derivative of Rhein that is indicated for the management of osteoarthritis. Diacerein exhibits poor dissolution in the GIT fluids and suffers from low bioavailability upon oral administration in addition to the laxative effect of Rhein metabolites. The aim of the present study was to develop novasomal vesicles with optimized entrapment efficiency and size to serve as a carrier for transdermal delivery of diacerein. Novasomal vesicles were prepared by thin film hydration method thin film hydration. The prepared vesicles were optimized utilizing different surfactant to cholesterol molar ration, sonication type, different sonication times and varying fatty acid level. The prepared vesicles were

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Publication Date
Thu Dec 28 2023
Journal Name
Farmacia
LASMIDITAN NANOEMULSION BASED IN SITU GEL INTRANASAL DOSAGE FORM: FORMULATION, CHARACTERIZATION AND IN VIVO STUDY
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Publication Date
Thu Jul 04 2024
Journal Name
Pharmaceutics
Formulation Development of Meloxicam Binary Ethosomal Hydrogel for Topical Delivery: In Vitro and In Vivo Assessment
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Abstract: The article aimed to formulate an MLX binary ethosome hydrogel for topical delivery to escalate MLX solubility, facilitate dermal permeation, avoid systemic adverse events, and compare the permeation flux and efficacy with the classical type. MLX ethosomes were prepared using the hot method according to the Box–Behnken experimental design. The formulation was implemented according to 16 design formulas with four center points. Independent variables were (soya lecithin, ethanol, and propylene glycol concentrations) and dependent variables (vesicle size, dispersity index, encapsulation efficiency, and zeta potential). The design suggested the optimized formula (MLX−Ethos−OF) with the highest desirability to perform the

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Publication Date
Sun Jun 03 2018
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Formulation and Evaluation of Acyclovir Microspheres
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The present study is to formulate and evaluate Acyclovir (ACV) microspheres using natural polymers like chitosan and sodium alginate. ACV is a DNA polymerase inhibitor used in treating herpes simplex virus infection and zoster varicella infections. Acyclovir is a suitable candidate for sustained-release (SR) administration as a result of its dosage regimen twice or thrice a day and relatively short plasma half-life (approximately 2 to 4 hours). Microspheres of ACV were prepared by an ionic dilution method using chitosan and sodium alginate as polymers. The prepared ACV microspheres were then subjected to FTIR, SEM, particle size, % yield, entrapment efficiency, in vitro dissolution studies and release kinetics mechanism. The FTI

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Publication Date
Sun Mar 26 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Formulation and Evaluation of Ezetimibe Nanoparticles
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The aim of this study is to formulate and evaluate ezetimibe nanoparticles using solvent antisolvent technology. Ezetimibe is a practically water-insoluble drug which acts as a lipid lowering drug that selectively inhibits the intestinal absorption of cholesterol and related phytosterols. Ezetimibe prepared as nano particles in order to improve its solubility and dissolution rate.

Thirty formulas were prepared and different stabilizing agents were used with different concentrations such as poly vinyl pyrrolidone (PVPK-30), poly vinyl alcohol (PVA), hydroxy propyl methyl cellulose E5 (HPMC), and poloxamer. The ratios of drug to stabilizers used to prepare the nanoparticles were 1: 2, 1:3 and 1:4.

The prepared nanoparticles

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Publication Date
Fri Nov 03 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences( P-issn 1683 - 3597 E-issn 2521 - 3512)
Study the Variables Affecting Formulation of Ethylcellulose-based Microsponges Loaded with Clobetasol
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Clobetasol propionate (CP) is a super potent corticosteroid widely used to treat various skin disorders such as atopic dermatitis and psoriasis. However, its utility for topical application is hampered due to its common side effects, such as skin atrophy, steroidal acne, hypopigmentation, and allergic contact dermatitis. Microsponge is a unique three-dimensional microstructure particle with micro and nano-meters-wide cavities, which can encapsulate both hydrophilic and lipophilic drugs providing increased efficacy and safety. The aim of the current study is to prepare and optimize clobetasol-loaded microsponges. The emulsion solvent diffusion method is used for the preparation of ethylcellulose (EC)-based microsponges. The impact of

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Publication Date
Thu May 31 2012
Journal Name
Journal Of Baghdad College Dentistry
An evaluation of water absorption of Giomer in comparison to other resin-based restorative materials
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Background: Polymeric composites have been widely used as dental restorative materials. A fundamental knowledge and understanding of the behavior of these materials in the oral cavity is essential to improve their properties and performance. The goal of this study was to measure water sorption of four composite resins containing different filler and resin matrix contents. Materials and method: Resin composite specimens giomer (Beautifil II) Filtek™ P90, Filtek™ Z350 XT, and Tetric N Ceram were prepared in a cylindrical mould of 3mm thickness and 6mm diameter (n=10) and light cured . All specimens placed in silica-gel desiccators at 37˚C for seven days, a constant weight was obtained. All samples were immersed in deionized distill

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Publication Date
Mon Dec 02 2013
Journal Name
International Journal Of Pharmacy And Pharmaceutical Sciences
Formulation and in vitro evaluation of rosuvastatin calcium niosomes
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Publication Date
Thu Jun 25 2020
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Formulation and In-vitro Evaluation of Itraconazole Floating Microparticles
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Itraconazole (ITZ) is an antifungal drug (BCSII) used for the treatment of local and systemic fungal infections. Furthermore, ITZ used as an antifungal prophylaxis for immunocompromised patients.

The objective of the study is to overcome the two problems of low and pH dependent solubility of ITZ by its preparation as floating microparticles.

Firstly, pH-dependent floating microparticles were prepared using oil in water solvent evaporation method, from which the best one (F7) selected as a best pH-dependent formula with composition of   ITZ (200mg),EC (800mg), HPMC 15cps (200mg) and safflower oil (2ml) .Then, F7 was compared with the selected Relatively pH-independent ITZ floating microparticles formula  wit

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