Olfa Ben Hadj Ayed

Bio: Olfa Ben Hadj Ayed is an academic researcher from University of Monastir. The author has co-authored 2 publications.

Quality-by-Design Approach Development, Characterization, and In Vitro Release Mechanism Elucidation of Nanostructured Lipid Carriers for Quetiapine Fumarate Oral Delivery

Abstract: The objective of this work was to develop a new nanostructured lipid carrier (NLC) formulation for the oral delivery of quetiapine fumarate (QTF) and assess the drug’s in vitro release mechanism through gastric and intestinal conditions. A preformulation study was conducted to select the most suitable components and solid-to-liquid lipid ratio for the formulation of nanoparticles. Then, a central composite design was employed to optimize the development of NLC and to study the effect of lipid and surfactant percentages on the physical characteristics of the preparation. The optimal formulation was subjected to physicochemical characterization and stability study. An in vitro release assay using simulated gastrointestinal fluids was performed to study the QTF release mechanism. The optimal formulation showed good particle size, PDI, and zeta potential of 179.2 ± 2.6 nm, 0.220 ± 0.020, and −33.63 ± 0.23 mV, respectively. The encapsulation efficiency and the loading capacity were 84.49 ± 1.25% and 2.6 ± 0.03%, respectively. DSC and FTIR analysis showed compatibility between QTF and other components of the formulation and successful encapsulation of the drug within lipid nanoparticles. The optimal formulation also showed good long-term stability at 4 °C storage temperature. The in vitro release of QTF followed the Korsmeyer-Peppas model. The study demonstrated that QTF was mainly released by diffusion mechanism in the gastric medium, and by erosion and anomalous transport in the intestinal medium. NLC represents a suitable formulation for the oral delivery of QTF. Further studies should investigate the oral absorption and lymphatic transport potential of the optimized formulation.

Self-emulsifying Drug Delivery System for Improved Dissolution and Oral Absorption of Quetiapine Fumarate: Investigation of Drug Release Mechanism and In-vitro Intestinal Permeability

Abstract: In this study, we focused on quetiapine fumarate (QTF), a class II BCS drug. QTF is an atypical antipsychotic used in the treatment of schizophrenia and bipolar disorders. Our objective was to develop a new QTF-loaded self-emulsifying drug delivery system (SEDDS) to improve the dissolution and absorption of the drug. An experimental design approach was used to develop and optimize QTF-loaded SEDDS. The optimized formulation was characterized for droplets size, zeta potential, PDI, and stability. It was then evaluated using an in-vitro combined test for dissolution and Everted gut sac technique. Mathematical modeling and Transmission electron microscopy (TEM) were used to elucidate the mechanism of release. The optimal formulation was type IIIB SEDDS, constituted of 9.1% of oleic acid, 51.6% of Tween®20, and 39.3% of Transcutol® P. It showed a droplets size of 144.8 ± 4.9nm with an acceptable PDI and zeta potential.For in-vitro evaluation tests, we noticed an enhancement of the dissolution rate of the optimal QTF-loaded SEDDS compared to the free drug (98.82 ± 1.24% for SEDDS after 30 min compared to 85.65 ± 2.5% for the pure drug). The release of QTF fitted with the Hopfenberg model indicating the drug was released by water diffusion and erosion mechanism. This result was confirmed by TEM images which showed a smaller droplet size after release. We also found an amelioration of the permeability of QTF of 1.69-fold from SEDDS compared to the free drug.Hence, the SEDDS formulation represented a new way to improve the dissolution and absorption of QTF.

Central Composite Optimization of Glycerosomes for the Enhanced Oral Bioavailability and Brain Delivery of Quetiapine Fumarate

Abstract: This study aimed to formulate and statistically optimize glycerosomal formulations of Quetiapine fumarate (QTF) to increase its oral bioavailability and enhance its brain delivery. The study was designed using a Central composite rotatable design using Design-Expert® software. The independent variables in the study were glycerol % w/v and cholesterol % w/v, while the dependent variables were vesicle size (VS), zeta potential (ZP), and entrapment efficiency percent (EE%). The numerical optimization process resulted in an optimum formula composed of 29.645 (w/v%) glycerol, 0.8 (w/v%) cholesterol, and 5 (w/v%) lecithin. It showed a vesicle size of 290.4 nm, zeta potential of −34.58, and entrapment efficiency of 80.85%. The optimum formula was further characterized for DSC, XRD, TEM, in-vitro release, the effect of aging, and pharmacokinetic study. DSC thermogram confirmed the compatibility of the drug with the ingredients. XRD revealed the encapsulation of the drug in the glycerosomal nanovesicles. TEM image revealed spherical vesicles with no aggregates. Additionally, it showed enhanced drug release when compared to a drug suspension and also exhibited good stability for one month. Moreover, it showed higher brain Cmax, AUC0–24, and AUC0–∞ and plasma AUC0–24 and AUC0–∞ in comparison to drug suspension. It showed brain and plasma bioavailability enhancement of 153.15 and 179.85%, respectively, compared to the drug suspension. So, the optimum glycerosomal formula may be regarded as a promising carrier to enhance the oral bioavailability and brain delivery of Quetiapine fumarate.

Fabrication and Assessment of Orodispersible Tablets Loaded with Cubosomes for the Improved Anticancer Activity of Simvastatin against the MDA-MB-231 Breast Cancer Cell Line

Abstract: Various factors limit the use of simvastatin as an anticancer drug. Therefore, this study aimed to analyse simvastatin (SIM)-loaded cubosome efficacy against breast cancer. SIM-loaded cubosomes were prepared using the emulsification method using different glyceryl monooleate, Pluronic F127 (PF-127), and polyvinyl alcohol (PVA) ratios. The best cubosomal formula was subjected to an in vitro cytotoxicity analysis using the human breast cancer cell line, MDA-MB-231 (MDA) (ATCC, HTB-26), and formulated as oral disintegrating tablets through direct compression. PF-127 and PVA positively affected drug loading, and the entrapment efficiency percentage of different SIM-cubosomal formulations ranged from 33.52% to 80.80%. Vesicle size ranged from 181.9 ± 0.50 to 316.6 ± 1.25 nm. PF-127 enhanced in vitro SIM release from cubosome formulations due to its solubilising action on SIM. The in vitro dissolution analysis indicated that SIM exhibited an initial dissolution of 10.4 ± 0.25% within the first 5 min, and 63.5 ± 0.29% of the loaded drug was released after 1 h. Moreover, cubosome formula F3 at 25 and 50 µg/mL doses significantly decreased MDA cell viability compared to the 12.5 µg/mL dose. The untreated SIM suspension and drug-free cubosomes at all doses had no significant influence on MDA cell viability compared to the control.

Formulasi dan Karakterisasi Self-Nanoemulsifying Drug Delivery System (SNEDDS) Esomeprazol Magnesium Trihidrat

Abstract: Esomeprazol magnesium trihidrat merupakan obat golongan proton pump inhibitor (PPI) yang dapat digunakan dalam pengobatan tukak lambung dengan menghambat sekresi asam lambung. Namun esomeprazol dikategorikan ke dalam BCS kelas 2 dengan kelarutan yang buruk dalam air sehingga dapat berdampak pada kemampuan disolusi dan bioavailabilitasnya. SNEDDS umum digunakan untuk meningkatkan kelarutan obat lipoflilik dimana SNEDDS merupakan campuran zat aktif, minyak, surfaktan, dan ko-surfaktan yang akan membentuk nanoemulsi minyak dalam air secara spontan ketika kontak dengan fase cair dengan agitasi yang ringan. Tujuan dari penelitian ini yaitu untuk mengetahui formula SNEDDS esomeprazol magnesium trihidrat yang paling baik serta mengetahui karakteristiknya. SNEDDS diformulasikan menggunakan fase minyak berupa VCO, surfaktan berupa tween 80, dan ko-surfaktan berupa PEG 400. Sediaan SNEDDS dilakukan evaluasi berupa persen transmitan, dispersibilitas, robustness, stabilitas termodinamika, indeks bias, ukuran globul, PDI, zeta potensial, dan uji disolusi. Hasil menunjukkan bahwa SNEDDS esomeprazol magnesium trihidrat dengan rasio minyak:Smix 1:6 dan perbandingan Smix 2:1 mampu membentuk nanoemulsi secara spontan dan stabil berdasarkan uji stabilitas termodinamika, dihasilkan rata-rata ukuran globul 78,03 nm, nilai PDI 0,667, nilai zeta potensial -14,57 mV, dan dapat meningkatkan kecepatan disolusi yang lebih baik dibandingkan bentuk murninya.