Sorbitol based powder precursor of cubosomes as an oral delivery system for improved bioavailability of poorly water soluble drugs

Nasr, Mohamed; Dawoud, Mohamed

doi:10.1016/j.jddst.2016.06.011

Cited by 34 publications

(15 citation statements)

References 41 publications

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“…These peaks are identical to the previously identified diffraction peaks for titanium dioxide [57]. Similarly, sorbitol exhibited crystallinity when it was used in the preparation of the filaments revealing a characteristic diffraction peak at 2θ of 11.9° [58] XRD data of filaments and tablets containing lisinopril dihydrate showed diffraction peaks at 2(θ)= 7.5°, 12.5°, 13.6°, and 16.5° which are the distinct diffraction peaks of the crystalline drug (Fig. 6A) [46].…”

Section: Resultssupporting

confidence: 83%

‘Temporary Plasticiser’: A novel solution to fabricate 3D printed patient-centred cardiovascular ‘Polypill’ architectures

Pereira

Isreb

Forbes

et al. 2019

European Journal of Pharmaceutics and Biopharmaceutics

162

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Hypertension and dyslipidaemia are modifiable risk factors associated with cardiovascular diseases (CVDs) and often require a complex therapeutic regimen. The administration of several medicines is commonly associated with poor levels of adherence among patients, to which World Health Organisation (WHO) proposed a fixed-dose combination unit (polypill) as a strategy to improve adherence. In this work, we demonstrate the fabrication of patient-specific polypills for the treatment of CVDs by fused deposition modelling (FDM) 3D printing and introduce a novel solution to meet critical quality attributes. The construction of poly(vinyl alcohol) (PVA)-based polypills containing four model drugs (lisinopril dihydrate, indapamide, rosuvastatin calcium and amlodipine besylate) was revealed for the first time. The impact of tablet architecture was explored using multi-layered and unimatrix structures. The novel approach of using distilled water as a 'temporary co-plasticiser' is reported and was found to significantly lower the extruding (90°C) and 3D printing (150°C) temperatures from 170°C and 210°C respectively, with consequent reduction in thermal stress to the chemicals. XRD indicated that lisinopril dihydrate and amlodipine besylate maintained their crystalline form while indapamide and rosuvastatin calcium were essentially amorphous in the PVA tablets. From the multilayer polypills, the release profile of each drug was dependent on its position in the multilayer.In addition to the multilayer architecture offering a higher flexibility in dose titration and a more adaptive solution to meet the expectations of patient-centred therapy, we identify that it also allows orchestrating the release of drugs of different physicochemical characteristics. Adopting such an approach opens up a pathway towards low-cost multidrug delivery systems such as tablets, stents or implants for wider range of globally approved actives.

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Section: Resultssupporting

confidence: 83%

‘Temporary Plasticiser’: A novel solution to fabricate 3D printed patient-centred cardiovascular ‘Polypill’ architectures

Pereira

Isreb

Forbes

et al. 2019

European Journal of Pharmaceutics and Biopharmaceutics

162

View full text Add to dashboard Cite

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“…6) Upon increasing pH to 6.8 to mimic the intestinal pH, % released of CB significantly (p<0.05) dropped to 66.82±4.12% after 6 h due to formation of unionized free base which have poor solubility. 50) On the contrary, optimized cubosome dispersion CL1 preserved %released of CB at 95.66±1.87% (p>0.05) which can be attributed to the high affinity of CB to the lipid layer of cubosomes due to its hydrophobic nature 39) thereby retaining CB in solubilized state 13,19) and preventing its precipitation.…”

Section: Determination Of Cb Solubility In Different Ph Mediamentioning

confidence: 95%

“…12) They also possess excellent loading properties, 13) facilitate absorption 14,15) and offer protection for drugs against degradation 16,17) thus making them an excellent choice for formulation of poorly soluble drugs orally. 18,19) Cubosomes can maintain the drug in a solubilized state in the gastrointestinal tract by entrapping drugs into the mixed micelles produced by the digestion of cubosomes, thereby enhance drug release and absorption leading to improved oral bioavailability. 13,20) Therefore, based on the above considerations, the main aim of this work is to enhance the solubility and the in vitro release of CB through the formulation of oral cubosome nanoparticles.…”

Section: Bleeding Timementioning

confidence: 99%

“…18,19) Cubosomes can maintain the drug in a solubilized state in the gastrointestinal tract by entrapping drugs into the mixed micelles produced by the digestion of cubosomes, thereby enhance drug release and absorption leading to improved oral bioavailability. 13,20) Therefore, based on the above considerations, the main aim of this work is to enhance the solubility and the in vitro release of CB through the formulation of oral cubosome nanoparticles. A 3 3 full factorial design was applied to study the effects of different formulation factors on particle size, entrapment efficiency (%EE) and percentage of CB release at 15 min in intestinal pH (%Q 15 ) of the resultant formulas.…”

Section: Bleeding Timementioning

confidence: 99%

“…12,41) The burst release pattern could be explained by the ability of the cubosome nanoparticles to keep the insoluble CB in a solubilized nano size state with the formation of concomitant large surface area for the diffusion of the drug from the nanoparticles upon exposure to the release medium in appropriate sink conditions. 20,42,43) While the tortuosity and the narrow pore size of the inner aqueous nanochannels of the cubic nanoparticles were responsible and contributed to the slowing down of the release in the second phase. 44,45) This pattern can be highly advantageous for the treatment of patients with high risk of myocardial infarction and stroke as the initial rapid drug release phase is important to achieve high CB concentration in a very short time, while the slow steady state release of the remaining product would provide successful drug delivery along the time.…”

Section: Determination Of Cb Solubility In Different Ph Mediamentioning

confidence: 99%

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Cubosomes as Oral Drug Delivery Systems: A Promising Approach for Enhancing the Release of Clopidogrel Bisulphate in the Intestine

et al. 2018

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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 3 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 15 min (%Q), and their morphology using transmission electron microscopy (TEM). The release of the optimized formula was compared in buffer transition media (pH 1.2 for 2 h then pH 6.8 for 6 h) 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±4.63 nm) 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±6.12 s) compared to Plavix (412.43±7.97 s). Thus, cubosomes proved to be a successful platform to enhance the intestinal release of CB and improve its absorption.

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Nature‐Inspired Design and Application of Lipidic Lyotropic Liquid Crystals

et al. 2019

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Amphiphilic lipids aggregate in aqueous solution into a variety of structural arrangements. Among the plethora of ordered structures that have been reported, many have also been observed in nature. In addition, due to their unique morphologies, the hydrophilic and hydrophobic domains, very high internal interfacial surface area, and the multitude of possible order−order transitions depending on environmental changes, very promising applications have been developed for these systems in recent years. These include crystallization in inverse bicontinuous cubic phases for membrane protein structure determination, generation of advanced materials, sustained release of bioactive molecules, and control of chemical reactions. The outstanding diverse functionalities of lyotropic liquid crystalline phases found in nature and industry are closely related to the topology, including how their nanoscopic domains are organized. This leads to notable examples of correlation between structure and macroscopic properties, which is itself central to the performance of materials in general. The physical origin of the formation of the known classes of lipidic lyotropic liquid crystalline phases, their structure, and their occurrence in nature are described, and their application in materials science and engineering, biology, medical, and pharmaceutical products, and food science and technology are exemplified. Amphiphilic LipidsThe ORCID identification number(s) for the author(s) of this article can be found under https://doi.

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Sorbitol based powder precursor of cubosomes as an oral delivery system for improved bioavailability of poorly water soluble drugs

Cited by 34 publications

References 41 publications

‘Temporary Plasticiser’: A novel solution to fabricate 3D printed patient-centred cardiovascular ‘Polypill’ architectures

‘Temporary Plasticiser’: A novel solution to fabricate 3D printed patient-centred cardiovascular ‘Polypill’ architectures

Cubosomes as Oral Drug Delivery Systems: A Promising Approach for Enhancing the Release of Clopidogrel Bisulphate in the Intestine

Nature‐Inspired Design and Application of Lipidic Lyotropic Liquid Crystals

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