Browsing by Author "El-Laithy H.M."

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Cubosomes as oral drug delivery systems: A promising approach for enhancing the release of clopidogrel bisulphate in the intestine
(Pharmaceutical Society of Japan, 2018) El-Laithy H.M.; Badawi A.; Abdelmalak N.S.; El-Sayyad N.; Department of Pharmaceutics and Industrial Pharmacy; Faculty of Pharmacy; Cairo University; Cairo; 11562; Egypt; Department of Pharmaceutics and Industrial Pharmacy; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA); 6th of October; 12582; Egypt
Clopidogrel bisulphate (CB) is a first line antiplatelet drug for treatment of myocardial infarction and stroke. Yet, its efficacy is limited by its poor solubility in intestinal pH, its main site of absorption. The main aim of this study is to enhance the intestinal release of CB by loading in cubosome nanoparticles. Glyceryl monooleate (GMO) based CB loaded cubosomes were prepared using a 33 factorial design to study the effect of polyvinyl alcohol (PVA), poloxamer 407 (PL407) concentrations and ratio of CB to the disperse phase on the average particle size, entrapment efficiency (%EE), in vitro release at 15min (%Q15), and their morphology using transmission electron microscopy (TEM). The release of the optimized formula was compared in buffer transition media (pH 1.2 for 2h then pH 6.8 for 6h) to free drug to study the effect of the changing pH in the gastrointestinal tract (GIT) on CB release. The antihaemostatic properties of the optimized formula were compared to the commercial product Plavix using bleeding time (BT) model in rabbits. The prepared cubosomes were in the nano range (115 6.47 to 248 4.63nm) with high %EE (91.22 4.09% to 98.98 3.21%). The optimized formula showed significantly higher (p<0.05) CB release in intestinal pH and preserved the high% released (95.66 1.87%) in buffer transition release study compared to free drug (66.82 4.12%) as well as significantly (p<0.05) higher antihaemostatic properties with longer BT (628.47 6.12s) compared to Plavix (412.43 7.97s). Thus, cubosomes proved to be a successful platform to enhance the intestinal release of CB and improve its absorption. 2018 The Pharmaceutical Society of Japan.
Novel self-nanoemulsifying self-nanosuspension (SNESNS) for enhancing oral bioavailability of diacerein: Simultaneous portal blood absorption and lymphatic delivery
(Elsevier, 2015) El-Laithy H.M.; Basalious E.B.; El-Hoseiny B.M.; Adel M.M.; Department of Pharmaceutics and Industrial Pharmacy; Faculty of Pharmacy; Cairo University; Cairo; Egypt; Department of Pharmaceutics and Industrial Pharmacy; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA); Cairo; Egypt; Duuepartment of Pharmaceutics; National Organization for Drug Control and Research; Cairo; Egypt
The application of self-nanoemulsified drug delivery system (SNEDDS) to improve bioavailability of diacerein (D) has been hampered by its large dose and limited solubility. This work aimed to prepare diacerein loaded self nanoemulsifying self nanosuspension (D-SNESNS) containing high drug load. D-SNESNS was prepared by homogenizing D into Maisine-based SNEDDS that gave the highest drug solubility. D-SNESNS was evaluated for particle size, zeta potential and in vitro dissolution. Significant increase of D solubility was observed from D-SNESNS (?309 ?g/mL) than traditional SNEDDS (?162 ?g/mL) due to the spontaneous simultaneous formation of nanoemulsion and nanosuspension (top-down approach). When exposed to water with mild agitation, the drug microparticles in D-SNESNS are temporarily surrounded by unsaturated aqueous layer (containing optimum concentrations of surfactant and co-solvent) that facilitates the erosion of the suspended drug particles into nanosized ones. Nanoemulsion-based nanosuspension (NENS) was confirmed using transmission electron microscopy and particle size analysis. D-SNESNS equivalent to 50 mg D exhibited complete and very rapid dissolution after 15 min in phosphate buffer pH 6.8 due to the existence of D as solubilized molecules inside nanoemulsion globules and nanosized suspended drug particles forming D-NENS. The relative bioavailabilities of rhein from D-SNESNS in rats with normal and blocked chylomicron flow were about 210% and 164%, respectively in comparison to aqueous D suspension. The significant increase in the dissolution, portal absorption and lymphatic delivery of D propose that SNESNS could be promising to improve oral bioavailability of poorly water soluble drugs that have limited drug load in SNEDDS. 2015 Elsevier B.V. All rights reserved.
Stabilizing excipients for engineered clopidogrel bisulfate procubosome derived in situ cubosomes for enhanced intestinal dissolution: Stability and bioavailability considerations
(Elsevier B.V., 2019) El-Laithy H.M.; Badawi A.; Abdelmalak N.S.; Elsayyad N.M.E.; Department of Pharmaceutics and Industrial Pharmacy; Faculty of Pharmacy; Cairo University; Egypt; Department of Pharmaceutics and Industrial Pharmacy; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA University); Egypt
Clopidogrel bisulfate (CB) is a golden antiplatelet treatment, yet its benefits are limited by its low bioavailability (<50%) caused by poor intestinal solubility and absorption. The present study aims to improve CB intestinal solubility and absorption through developing a novel stable dry CB procubosomes tablets ready to disintegrate and re-disperse upon dilution in the GIT forming in situ CB cubosome nanoparticles while simultaneously overcome the poor stability of conventional cubosome dispersion at room temperature. Glyceryl monooleate based CB cubosome dispersion was prepared using Poloxamer 407 as surfactant, freeze dried using different stabilizing excipients (dextrose, mannitol and avicel) then compressed into procubosome tablets. The effect of excipient's physicochemical properties on the flowability, in vitro dissolution and stability at accelerated conditions (40 � 2 �C/75 � 5% RH) were evaluated. The prepared procubosomes exhibited an excipient type dependent dissolution profile where Avicel based procubosome tablet CF2 showed the highest in vitro dissolution profile among other excipients used during the freeze drying process. Upon transition to intestinal pH of 6.8 to mimic the drug absorption site, CF2 procubosome Avicel tablet, was able to preserve the enhanced CB release profile (99.6 � 6.92%) compared to commercial Plavix� where, CB dissolved % dropped dramatically to 79.1 � 2.45%. After storage for six months, CF2 retained the fresh tablet drug content of 98.5 � 5.82% and dissolution properties. Moreover, following oral administration in rabbits, CF2 showed higher relative bioavailability (153%) compared to commercial Plavix� with significant higher Cmax,shorter tmax, as well as enhanced antiplatelet activity. � 2019 Elsevier B.V.