Search

Manar Adel Abdelbari,1 Shereen Sameh El-mancy,1 Ahmed Hassen Elshafeey,2 Aly Ahmed Abdelbary2,3 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October 6 University, Giza, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 3School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, Cairo, EgyptCorrespondence: Aly Ahmed AbdelbaryDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini, Cairo, 11562, EgyptTel +20 1149005526Email aly.abdelbary@pharma.cu.edu.egPurpose: The aim of this study was to encapsulate clotrimazole (CLT), an antifungal drug with poor water solubility characteristics, into spanlastics (SPs) to provide a controlled ocular delivery of the drug.Methods: Span 60 was used in the formulation of SPs with Tween 80, Pluronic F127, or Kolliphor RH40 as an edge activator (EA). The presence of EA offers more elasticity to the membrane of the vesicles which is expected to increase the corneal permeation of CLT. SPs were prepared using ethanol injection method applying 32 complete factorial design to study the effect of formulation variables (ratio of Span 60: EA (w/w) and type of EA) on SPs characteristics (encapsulation efficiency percent (EE%), average vesicle size (VS), polydispersity index (PDI) and zeta potential (ZP)). Design-Expert software was used to determine the optimum formulation for further investigations.Results: The optimum formulation determined was S1, which contains 20 mg of Tween 80 used as an EA and 80 mg of Span 60. S1 exhibited EE% = 66.54 ± 7.57%, VS = 206.20 ± 4.95 nm, PDI = 0.39 ± 0.00 and ZP = − 29.60 ± 0.99 mV. S1 showed highly elastic sphere-shaped vesicles. Furthermore, S1 displayed a sustained release profile and a higher ex vivo permeation across rabbit cornea relative to CLT suspension. Also, S1 revealed superior inhibition of Candida albicans development compared to CLT suspension applying 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction technique. Moreover, in vivo histopathological examination assured the safety of S1 after ophthalmic application in mature male albino rabbits.Conclusion: Overall, the outcomes revealed the marked efficacy of SPs for ocular delivery of CLT.Keywords: clotrimazole, spanlastics, edge activators, XTT reduction technique, ocular drug delivery

Fatma Mohamed Elsenosy,1 Ghada Ahmed Abdelbary,2 Ahmed Hassen Elshafeey,2 Ibrahim Elsayed,2,3 Ahmed Roshdy Fares2 1Department of Clinical Pharmacy, Children’s Cancer Hospital, Cairo57357, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 3Department of Pharmaceutical Sciences, College of Pharmacy and Thumbay Research Institute for Precision Medicine, Gulf Medical University, Ajman, United Arab EmiratesCorrespondence: Ahmed Roshdy FaresDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El Aini Street, Cairo 11562, EgyptTel +20 12 88285866Email ahmed.roshdy@pharma.cu.edu.egPurpose: Duloxetine (DLX) is dual serotonin and norepinephrine reuptake inhibitor suffering from limited bioavailability (≈ 40%) due to extensive hepatic metabolism. This work aims to formulate and evaluate DLX intranasal thermoreversible cubosomal gels to enhance its bioavailability and ensure efficient brain targeting.Materials and Methods: Cubo-gels were prepared by 33 central composite design with three independent factors, lipid ratio (glycerol monooleate: glycerol tripalmitate), Pluronic F127%, and Pluronic F68%. The prepared formulations were evaluated for their particle size (PS), gelling temperature (GT), entrapment efficiency (EE%), and in vitro release. The cubo-gel with the highest desirability (0.88) was chosen as the optimized formulation. DLX cubo-gel was evaluated using differential scanning calorimetry, Fourier-transform infrared spectroscopy, X-ray powder diffraction, and transmission electron microscopy. Cytotoxicity study, ex vivo permeation study and in vivo bio-distribution study were conducted to evaluate the safety and efficacy of brain targeting.Results: The optimum cubo-gel was composed of 3.76 lipid ratio, 20% w/v PF127, and 5% w/v PF68. It had PS of 265.13 ± 9.85 nm, GT of 32 ± 0.05°C, EE% of 98.13 ± 0.50%, and showed controlled release behavior where 33% DLX was released within 6 hrs. The plain in situ cubo-gel had a significantly higher IC50 compared to DLX solution and DLX-loaded in situ cubo-gel. The ex vivo permeation study showed 1.27 enhancement in the drug permeation from DLX in situ cubo-gel. According to the in vivo bio-distribution study in plasma and brain, the intranasal DLX in situ cubo-gel showed a 1.96 fold improvement in brain bioavailability compared to the intranasal solution. Its BTE% and DTP% were 137.77 and 10.5, respectively, indicating efficient brain targeting after intranasal administration.Conclusion: Accordingly, intranasal DLX in situ cubo-gel can be considered as an innovative nano-carrier delivery system for bioavailability enhancement and efficient brain targeting of DLX to maximize its effect.Keywords: duloxetine, central composite design, cubosomes, thermoreversible in situ gel, intranasal, brain targeting