19 research outputs found
Brief Effect of a Small Hydrophobic Drug (Cinnarizine) on the Physicochemical Characterisation of Niosomes Produced by Thin-Film Hydration and Microfluidic Methods
No full textfirst_pagesettings
Open AccessArticle
Brief Effect of a Small Hydrophobic Drug (Cinnarizine) on the Physicochemical Characterisation of Niosomes Produced by Thin-Film Hydration and Microfluidic Methods
by Li Key YeoOrcID,Temidayo O. B. Olusanya,Cheng Shu Chaw andAmal Ali Elkordy *OrcID
School of Pharmacy and Pharmaceutical Sciences, University of Sunderland, Sunderland SR1 3SD, UK
*
Author to whom correspondence should be addressed.
Pharmaceutics 2018, 10(4), 185; https://doi.org/10.3390/pharmaceutics10040185
Received: 20 July 2018 / Revised: 5 October 2018 / Accepted: 9 October 2018 / Published: 13 October 2018
(This article belongs to the Special Issue Non-Ionic Surfactant Vesicles for Drug Delivery)
Download PDF Browse Figures
Abstract
Novel niosomal formulations containing cinnarizine were developed to enhance its drug characteristics. In this work, niosomes (non-ionic surfactant vesicles) were prepared by conventional thin-film hydration (TFH) and microfluidic (MF) methods with sorbitan monostearate (Span® 60), cholesterol, and co-surfactants (Cremophor® ELP, Cremophor® RH40 and Solutol® HS15) as key excipients. The aim was to study the effect of cinnarizine on the characteristics of different niosomal formulations manufactured by using different methods. For effective targeted oral drug delivery, the efficacy of niosomes for therapeutic applications is correlated to their physiochemical properties. Niosome vesicles prepared were characterised using dynamic light scattering technique and the morphology of niosomes dispersion was characterised using optical microscopy. Dialysis was carried out to purify niosome suspensions to determine drug loading and drug release studies was performed to study the potential use of niosomal systems for cinnarizine
Mixed solvent system as binder for the production of silicified microcrystalline cellulose-based pellets
No full textABSTRACT: Silicified microcrystalline cellulose pellets with hydroxypropyl methylcellullose (HPMC) as modifier were prepared using a
mixed solvent as liquid binder. Pellets were produced using extrusion-spheronization with a mixed solvent consisting of water and isopropanol
as liquid binder. The key spheronization aid was Prosolv® SMCC 90. Low viscosity grade HPMC was incorporated aiming to
modify release of indometacin. Physical characteristics including breaking load, apparent density and flow properties, particle size distribution
and shape were determined. Drug loaded pellets were also tested for dissolution profiles. By adjusting liquid binder property, at
isopropanol to water ratio of 3.5 to 6.5, pellets of desirable size and shape with reasonable yields were obtained. Pellets exhibited good
flow property and they were mechanically strong. Pellet with higher HPMC content displayed a faster drug dissolution profile. This was
because low viscosity grade HPMC was not enough to create strong gel. Instead hydration of HPMC molecules increased matrix’s
hydrophilicity and weakened the structure of pellet faster. The release of indometacin was partly based on the erosion of hydrated
matrix. The presence of HPMC in the pellets would require a mixed solvent to produce desirable shape. Incorporation of HPMC had
modified drug release from the pellets without further coating. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47924
The gastric emptying and drug absorption from liquid formulations of 4-aminosalicylic acid
No full textThe fate of a 500mg dose 4-aminosalicylic acid (4ASA) liquid formulation was investigated in humans. Buffered pH3 and 7 oral liquid formulations were designed to provide adequate evaluation of the gastric emptying using applied potential tomography (APT). The gastric luminal pH profiles were monitored using a pH-sensitive radiotelemetry capsule and blood was sampled over 8 hours. In a further series of experiments, the gastric luminal acid secretion was restricted by ranitidine pre-treatment, to test the performance of APT and to observe the influence on the absorption profile of 4ASA. The content of 4ASA and its metabolites in the blood were analysed by HPLC assay. An intravenous administration of 4ASA was used as a reference to calculate the pharmacokinetic profiles with a deconvolution technique based on maximum entropy theory and a mass balance technique based on Wagner-Nelson compartmental theory. The gastric emptying parameters were determined using statistical moments to provide a mean gastric residence time. The results showed that the performance of APT was not affected by physiological acid secretion. The ranitidine pre-treatment gave a full acid suppression until after the gastric emptying process of the oral liquid was completed. The shape of the blood level curves of 4ASA liquid formulations was influenced by the gastric emptying rate, which in turn was controlled by the duodenum acid feedback mechanism. The gastric emptying rate of pH3 4ASA formulation was delayed and hence an extended 4ASA mean absorption time was observed. The elimination rate of 4ASA was rapid when compared to its major metabolite, N-acetyl-4ASA (AASA). The bioavailability of 4ASA and AASA of the different formulations was restricted, with a mean average value ranging from 61 to 85% depending on treatment. The results derived from the maximum entropy approach differed from those of the Wagner- Nelson method. The limited intravenous data points restricted the calculations. The 4ASA absorption rate distribution profiles, calculated using the maximum entropy approach, in some cases displayed a double peak phenomenon, which demonstrated the complexity in disposition even for of a simple oral liquid formulation of 4ASA. This phenomenon was not observed with the Wagner-Nelson method. The clearance and rate constant values of the current study differed from previous reported cases, where much higher doses and different dosage forms had been used
The role of palliative radiotherapy for haemostasis in unresectable gastric cancer:a single-institution experience
No full textTo evaluate the outcomes of patients with gastric cancer bleeding who had been treated with palliative radiotherapy with haemostatic intent
The Effects of Hydration Parameters and Co-Surfactants on Methylene Blue-Loaded Niosomes Prepared by the Thin Film Hydration Method
No full textAbstract: This work aimed to investigate and optimise the effects of co-surfactants, hydration volume, and time on the entrapment of methylene blue (MB) within niosomes and the vesicle sizes of MB-loaded niosomes upon different storage temperatures. Niosomes were prepared by the thin film hydration method followed by gel permeation chromatography to obtain purified niosome suspensions. The probe sonication method was used to reduce the niosome vesicle size and distribution. Highest entrapment efficiencies (%EE) were determined for niosomal formulations containing Span® 60, cholesterol, and Cremophor® ELP (E2 and E3), which were prepared with a hydration volume of 5 mL. The hydration time was 15 min for E2 and 60 min for E3 (%EE = 40.1 ± 7.9% and 32.9 ± 10.1% for E3 and E2, respectively). The final lipid contents in the formulations were shown to have an impact on %EE
Insights into Asymmetric Liposomes as a Potential Intervention for Drug Delivery Including Pulmonary Nanotherapeutics
No full textLiposome-based drug delivery systems are nanosized spherical lipid bilayer carriers that can encapsulate a broad range of small drug molecules (hydrophilic and hydrophobic drugs) and large drug molecules (peptides, proteins, and nucleic acids). They have unique characteristics, such as a self-assembling bilayer vesicular structure. There are several FDA-approved liposomal-based medicines for treatment of cancer, bacterial, and viral infections. Most of the FDA-approved liposomal-based therapies are in the form of conventional “symmetric” liposomes and they are administered mainly by injection. Arikace® is the first and only FDA-approved liposomal-based inhalable therapy (amikacin liposome inhalation suspension) to treat only adults with difficult-to-treat Mycobacterium avium complex (MAC) lung disease as a combinational antibacterial treatment. To date, no “asymmetric liposomes” are yet to be approved, although asymmetric liposomes have many advantages due to the asymmetric distribution of lipids through the liposome’s membrane (which is similar to the biological membranes). There are many challenges for the formulation and stability of asymmetric liposomes. This review will focus on asymmetric liposomes in contrast to conventional liposomes as a potential clinical intervention drug delivery system as well as the formulation techniques available for symmetric and asymmetric liposomes. The review aims to renew the research in liposomal nanovesicle delivery systems with particular emphasis on asymmetric liposomes as future potential carriers for enhancing drug delivery including pulmonary nanotherapeutics
Overcoming Oral Cavity Barriers for Peptide Delivery Using Advanced Pharmaceutical Techniques and Nano-Formulation Platforms
No full textTherapeutic peptides have gained significant attention due to their high specificity, potency, and safety profiles in treating various diseases. However, their clinical application via the oral route remains challenging. Peptides are inherently unstable in the gastrointestinal environment, where they are rapidly degraded by proteolytic enzymes and acidic pH, leading to poor bioavailability. Additionally, their large molecular size and hydrophilicity restrict passive diffusion across the epithelial barriers of the gastrointestinal tract. These limitations have traditionally necessitated parenteral administration, which reduces patient compliance and convenience. The oral cavity, comprising the buccal and sublingual mucosa, offers a promising alternative for peptide delivery. Its rich vascularization allows for rapid systemic absorption while bypassing hepatic first-pass metabolism. Furthermore, the mucosal surface provides a relatively permeable and accessible site for drug administration. However, the oral cavities also present significant barriers: the mucosal epithelium limits permeability, the presence of saliva causes rapid clearance, and enzymes in saliva contribute to peptide degradation. Therefore, innovative strategies are essential to enhance peptide stability, retention, and permeation in this environment. Nanoparticle-based delivery systems, including lipid-based carriers such as liposomes and niosomes, as well as polymeric nanoparticles like chitosan and PLGA, offer promising solutions. These nanocarriers protect peptides from enzymatic degradation, enhance mucoadhesion to prolong residence time, and facilitate controlled release. Their size and surface properties can be engineered to improve mucosal penetration, including through receptor-mediated endocytosis or by transiently opening tight junctions. Among these, niosomes have shown high encapsulation efficiency and sustained release potential, making them particularly suitable for oral peptide delivery. Despite advances, challenges remain in translating these technologies clinically, including ensuring biocompatibility, scalable manufacturing, and patient acceptance. Nevertheless, the oral cavity’s accessibility, combined with nanotechnological innovations, offers a compelling platform for personalized, non-invasive peptide therapies that could significantly improve treatment outcomes and patient quality of life
Feasibility of Using Gluconolactone, Trehalose and Hydroxy-Propyl Gamma Cyclodextrin to Enhance Bendroflumethiazide Dissolution Using Lyophilisation and Physical Mixing Techniques
No full textPurpose: Hydrophobic drugs are facing a major challenge in dissolution rate enhancement and solubility in aqueous solutions; therefore, a variety of methods have been used to improve dissolution rate and/or solubility of bendroflumethiazide as a model hydrophobic drug. Methods: In this study, two main methods (physical mixing and lyophilisation) were used with gluconolactone, hydroxyl propyl γ-ccyclodextrin, and trehalose to explore this challenge. Bendroflumethiazide, practically insoluble in water, was mixed with one of the three excipients gluconolactone, hydroxyl propyl γ-cyclodextrin, and trehalose in three different ratios 1:1, 1:2, 1:5. To the best of our knowledge, the dissolution of the drug has not been previously enhanced by using either these methods or any of the used excipients. Samples containing drug and each of the excipients were characterized via dissolution testing, Fourier Transform infra-red spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Results: The used methods showed a significant enhancement in dug dissolution rate; physical mixing significantly, p < 0.05, increased the percentage of the drug released with time; for example, bendroflumethiazide dissolution in distilled water was improved from less than 20% to 99.79% within 90 min for physically mixed drug-cyclodextrin 1:5. The lyophilisation process was enhanced and the drug dissolution rate and the highest drug dissolution was achieved for (drug-gluconolactone 1:1) with 98.98% drug release within 90 min. Conclusions: the physical mixing and freeze drying processes significantly increased the percentage of drug release with time
Development of vancomycin, a glycopeptide antibiotic, in a suitable nanoform for oral delivery.
No full textBacterial infections caused by resistant strains have emerged as one of the most significant life-threatening challenges. Developing alternatives to conventional antibiotic formulations is crucial to overcoming these challenges. Vancomycin HCl (VCM) is a glycopeptide antibiotic used for Gram-positive bacterial infections that must be given intravenously for systemic infections since it cannot pass through the gut wall due to its chemical structure and characteristics. The aim of this research is to develop VCM in a niosomal nanoform to then be encapsulated in fast-disintegrating oral films for effective delivery to enhance the application of vancomycin-loaded niosomes for treating oral infections and to be used in dental treatments. The formulation of niosomes encapsulating VCM was conducted with various ratios of Span 40, Span 60, and cholesterol as well as Kolliphor RH40 and Kolliphor ELP as co-surfactants using the microfluidic technique. The prepared niosomes were characterised using dynamic light scattering (DLS) for their size determination; high-pressure liquid chromatography, HPLC, for drug encapsulation efficiency determination; and the agar diffusion method for the determination of the antibacterial efficacy of the VCM niosomes against Bacillus subtilis. The niosomal formulation was then incorporated into polyvinyl alcohol (PVA) film, and the properties of the oral film were characterised by in vitro assays. The vancomycin-loaded niosomes produced with optimal conditions exhibited small diameter with acceptable polydispersity index, and drug encapsulation efficiency. This study presents multifunctional niosomes loaded with VCM, which demonstrated efficient in vitro activity against Gram-positive bacteria upon the slow release of VCM from niosomes, as demonstrated by the dissolution test. Oral films containing VCM niosomes demonstrated uniform weights and excellent flexibility with high foldability and a rapid disintegration time of 105 ± 12 s to release the niosomal content. This study showed that the microfluidic approach could encapsulate VCM, a peptide in salt form, in surfactant-based niosomal vesicles with a narrow size distribution. The incorporation of niosomes into fast-disintegrating film provides a non-invasive and patient-friendly alternative for treating bacterial infections in the oral cavity, making it a promising approach for dental and systemic applications
Liposomes and Their Therapeutic Applications in Enhancing Psoriasis and Breast Cancer Treatments
No full textPsoriasis and breast cancer are two examples of diseases where associated inflammatory pathways within the body’s immune system are implicated. Psoriasis is a complex, chronic and incurable inflammatory skin disorder that is primarily recognized by thick, scaly plaques on the skin. The most noticeable pathophysiological effect of psoriasis is the abnormal proliferation of keratinocytes. Breast cancer is currently the most diagnosed cancer and the leading cause of cancer-related death among women globally. While treatments targeting the primary tumor have significantly improved, preventing metastasis with systemic treatments is less effective. Nanocarriers such as liposomes and lipid nanoparticles have emerged as promising drug delivery systems for drug targeting and specificity. Advances in technologies and drug combinations have emerged to develop more efficient lipid nanocarriers to include more than one drug in combinational therapy to enhance treatment outcomes and/or relief symptoms for better patients’ quality of life. Although there are FDA-approved liposomes with anti-cancer drugs for breast cancer, there are still unmet clinical needs to reduce the side effects associated with those nanomedicines. Hence, combinational nano-therapy may eliminate some of the issues and challenges. Furthermore, there are no nanomedicines yet clinically available for psoriasis. Hence, this review will focus on liposomes encapsulated single and/or combinational therapy to augment treatment outcomes with an emphasis on the effectiveness of combinational therapy within liposomal-based nanoparticulate drug delivery systems to tackle psoriasis and breast cancer. This review will also include an overview of both diseases, challenges in delivering drug therapy and the roles of nanomedicines as well as psoriasis and breast cancer models used for testing therapeutic interventions to pave the way for effective in vivo testing prior to the clinical trials
