Development and optimisation of spironolactone nanoparticles for enhanced dissolution rates and stability

Stable solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) formulations to enhance the dissolution rates of poorly soluble drug spironolactone (SP) were being developed. Probe ultra-sonication method was used to prepare SLNs and NLCs. All NLCs contained stearic acid (solid lipid carrier) and oleic acid (liquid lipid content), whereas, SLNs were prepared and optimised by using the solid lipid only. The particles were characterised in terms of particle size analysis, thermal behaviour, morphology, stability and in vitro release. The zeta sizer data revealed that the increase in the concentration of oleic acid in the formulations reduced the mean particle size and the zeta potential. The increase in concentration of oleic acid from 0 to 30% (w/w) resulted in a higher entrapment efficiency. All nanoparticles were almost spherically shaped with an average particle size of about ∼170 nm. The DSC traces revealed that the presence of oleic acid in the NLC formulations resulted in a shift in the melting endotherms to a higher temperature. This could be attributed to a good long-term stability of the nanoparticles. The stability results showed that the particle size remained smaller in NLC compared to that of SLN formulations after 6 months at various temperatures. The dissolution study showed about a 5.1- to 7.2-fold increase in the release of the drug in 2 h compared to the raw drug. Comparing all nanoparticle formulations indicated that the NLC composition with a ratio of 70:30 (solid:liquid lipid) is the most suitable formulation with desired drug dissolution rates, entrapment efficiency and physical stability

Personalised dosing: Printing a dose of one's own medicine

© 2015 Elsevier B.V. All rights reserved. Ink-jet printing is a versatile, precise and relatively inexpensive method of depositing small volumes of solutions with remarkable accuracy and repeatability. Although developed primarily as a technology for image reproduction, its areas of application have expanded significantly in recent years. It is particularly suited to the manufacture of low dose medicines or to short production runs and so offers a potential manufacturing solution for the paradigm of personalised medicines. This review discusses the technical and clinical aspects of ink-jet printing that must be considered in order for the technology to become widely adopted in the pharmaceutical arena and considers applications in the literature

Drug delivery innovations to address global health challenges for pediatric and geriatric populations (through improvements in patient compliance)

Despite significant advances in pharmaceutical and biotechnological drug discovery, the global population is plagued with many challenging diseases. These are further compounded by anticipated explosion in an ageing population, which presents several problems such as polypharmacy, dysphagia, and neurologic conditions, resulting in noncompliance and disease complications. For antibiotics, poor compliance, can result in development of drug-resistant infections which can be fatal. Furthermore, children, especially, in developing countries die unnecessarily from easily treatable diseases (e.g., malaria), due to poor compliance arising from bitter taste and inability to swallow currently available medication. Although some of these challenges require the discovery of new drug compounds, a significant number can be resolved by employing pharmaceutics approaches to reduce the incidence of poor patient compliance. Such solutions are expected to make swallowing easier and reduce the need to swallow several solid medications, which is difficult for vulnerable pediatric and geriatric patients. This commentary will explore the current state of the art in the use of drug delivery innovations to overcome some of these challenges, taking cues from relevant regulatory agencies such as the Food and Drug Administration, the European Medicines Agency, World Health Organization, and the peer-reviewed scientific and clinical literature

Lipid nanocarriers loaded with natural compounds: Potential new therapies for age related neurodegenerative diseases?

Article in pressAge related neurodegenerative disorders (ARND) are presented as the most debilitating and challenging diseases associated with the central nervous system. Despite the advent of active molecules with a positive role on neurodegenerative mechanisms, many of the current therapeutic strategies remain ineffective in treating or preventing ARND. Lipid nanocarriers have emerged as efficient delivery systems with the capability to cross biological barriers, especially the blood brain barrier (BBB). Also, when associated to natural compounds, lipid nanocarriers have demonstrated to be an interesting alternative to ARND therapies with multiple beneficial effects. This comprehensive review focus on state-of-the-art lipid based nanocarriers for the delivery of natural compounds targeting neurodegeneration. A critical analysis of published reports will be also provided giving indications to researchers about the most promising ARND nanotherapy strategies.Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding UID/FIS/04650/2013. Marlene Lúcio acknowledges the exploratory project funded by FCT with the reference IF/00498/2012. Telma Soares acknowledges COMPETE 2020 “Programa Operacional Competitividade e internacionalização”info:eu-repo/semantics/publishedVersio

Itraconazol-Loaded Nanostructured Lipid Carriers (NLC) for Pulmonary Application

Introduction: Aspergillosis is a common fungal infection in falcons. Standard treatment, systemic application of Itraconazol, is limited due to hepatotoxicity. [...

Nanosuspensionen und Nanostrukturierte Lipid Carrier zur dermalen Applikation

The synthesis of the new sPLA2 inhibitors PX-18 and PX-13 was optimized, the compounds characterized and a reversed-phase HPLC-UV method for quantitative analysis developed and validated. PX-18 and PX-13 are poorly soluble in water. To overcome this problem they were formulated as nanosuspensions using high pressure homogenization. Applying 20 homogenization cycles at 1500 bar at 5°C, PX-18 nanosuspensions with an active content of 1%, 5% and 10%, stabilized with 1% Tween 80, with a particles size below 1 µm could be achieved. For the 1% PX-18 nanosuspension an average particle size measured by PCS < 50 nm was obtained. Melting 1% or 5% PX-13 in a 2% Plantacare® 2000 solution and homogenizing the obtained emulsion applying 3 homogenization cycles at 500 bar at 95°C, led to nanosuspensions with particles sizes well in the nanometer range. For PX-18 and PX-13 an increase in saturation solubility and in dissolution velocity could be shown by decreasing the particle size from the micrometer range to the nanometer range. The best physical stability was found for PX-18 nanosuspensions stored at 5°C and for PX-13 nanosuspensions stored at 25°C. The nanosuspensions were chemical stable at these storage temperatures. The dermal and ocular safety of PX-18 and PX-13 was evaluated on primary human keratinocytes and fibroblasts monolayer cell cultures by MTT and Neutral red assay, with the reconstructed human epidermis model EPISKIN and the HET-CAM test. It could be shown that the sPLA2 inhibitors PX-18 and PX-13 as well as the according nanosuspensions with an active content of 5% can be classified as non irritant to the skin and non/slightly irritant to the eye. Coenzyme Q10-loaded NLC and o/w emulsion were prepared by high pressure homogenization. A similar particle size, well within the nanometer range, was obtained for both formulations. The carrier systems showed a good physical stability. The chemical stability of coenzyme Q10 under light exposure was best for the NLC formulation. Investigating the occlusive properties of coenzyme Q10 containing NLC, o/w emulsion and liquid paraffin, film formation could be shown with the in vitro, ex vivo and in vivo occlusion test for NLC. In the in vitro and ex vivo test coenzyme Q10-loaded NLC performed a similar occlusivety like highly occlusive liquid paraffin whereas the coenzyme Q10-loaded o/w emulsion was much less occlusive. In vivo the formation of a dense film on the skin could be shown by the reduction of the Corneometer values. No significant difference in the release of coenzyme Q10 from NLC and o/w emulsion was found whereas the release of coenzyme Q10 from liquid paraffin was significant lower in vitro. The coenzyme Q10 release followed zero-order release kinetic from all 3 formulations. Comparing the penetration of coenzyme Q10 from NLC, o/w emulsion and liquid paraffin into the stratum corneum, it was found that the penetration of coenzyme Q10 from NLC was significant higher than from the other two formulations. The penetration of coenzyme Q10 from liquid paraffin was the lowest. The effect on the skin hydration was evaluated in vivo after repetitive application of a cream containing coenzyme Q10-loaded NLC and a conventional o/w cream containing the same amount of coenzyme Q10 and having the same lipid content. Both creams increased the skin hydration significantly within 7 days. A significant higher skin hydration was found in the test areas of the NLC containing cream after 28 and 42 days.Die Synthese der neuen sPLA2 Inhibitoren PX-18 und PX-13 wurde optimiert, die Wirkstoffe charakterisiert und eine Reversed-Phase-HPLC-UV Methode entwickelt und validiert. PX-18 und PX-13 sind praktisch unlöslich in Wasser. Um das Löslichkeitsproblem zu umgehen, wurden Nanosuspensionen mittels Hochdruckhomogenisation hergestellt. Nanosuspensionen mit einem Gehalt von 1%, 5% und 10% PX-18, stabilisiert mit 1% Tween 80, mit einer Partikelgröße < 1 µm konnten mit 20 Homogenisationszyklen mit einem Druck von 1500 bar bei 5°C hergestellt werden. PCS Messungen ergaben eine Partikelgröße < 50 nm für die 1%ige Nanosuspension. Das Schmelzen von 1% bzw. 5% PX-13 in einer wässrigen 2%igen Plantacare® 2000 Lösung und die nachfolgende Homogenisation der erhaltenen Emulsion bei 500 bar und 95°C mit 3 Zyklen, führte zu Nanosuspensionen mit einer zufrieden stellenden Partikelgröße. Für PX-18 und PX-13 konnte ein Anstieg der Sättigungslöslichkeit und der Lösungsgeschwindigkeit gezeigt werden, wenn die Partikelgröße vom Mikrometer- in den Nanometerbereich überführt wurde. Die beste physikalische Stabilität wurde erhalten, wenn PX-18 Nanosuspensionen bei 5°C und PX-13 Nanosuspensionen bei 25°C gelagert wurden. Bei diesen Lagertemperaturen waren die Nanosuspensionen chemisch stabil. Das Gefahrenpotential von PX-18 und PX-13 an der Haut und am Auge wurde an Monolayer-Zellkulturen primärer, humaner Keratinozyten und Fibroblasten mit dem MTT und Neutralrot Test, mit dem rekonstruierten humanen Epidermismodell EPISKIN und dem HET-CAM Test untersucht. Es konnte gezeigt werden, dass die sPLA2 Inhibitoren PX-18 und PX-13 sowie die Nanosuspensionen mir einem Gehalt von 5% nicht reizend an der Haut und nicht/leicht irritierend am Auge sind. Mit Hochdruckhomogenisation wurden Coenzym Q10-beladene NLC und eine O/W-Emulsion hergestellt. Es wurde für beide Trägersysteme eine ähnliche Partikelgröße im Nanoeterbereich erhalten. Die Trägersysteme waren physikalisch stabil. Die beste Stabilisierung von Coenzym Q10 unter Lichteinfluss zeigten die NLC. Bei Untersuchungen der okklusiven Eigenschaften konnte eine Filmbildung in vitro, ex vivo und in vivo für die NLC gezeigt werden. Im in vitro und ex vivo Okklusionstest ergab sich für die NLC eine vergleichbare Okklusivität wie für hoch okklusives flüssiges Paraffin, während die O/W-Emulsion weitaus geringere okklusive Eigenschaften hatte. In vivo konnte die Bildung eines dichten Films auf der Haut über die Abnahme der Corneometerwerte gezeigt werden. Kein signifikanter Unterschied im Freisetzungsverhalten von Coenzym Q10 aus den NLC und der O/W-Emulsion konnte in vitro gefunden werden, während die Freisetzung aus flüssigem Paraffin signifikant geringer war. Die Freisetzung aus allen 3 Formulierungen verlief nach einer Freisetzungskinetik 0. Ordnung. Beim Vergleich der Penetration von Coenzym Q10 ins Stratum corneum ergab sich, dass die Penetration von Coenzym Q10 aus NLC signifikant höher war als aus der O/W-Emulsion und flüssigem Paraffin. Die geringste Menge penetrierte aus flüssigem Paraffin. Der Effekt auf die Hautfeuchtigkeit nach wiederholter Anwendung einer Creme mit Coenzym Q10-beladene NLC und einer konventionellen O/W Creme mit dem gleichen Coenzym Q10- und Fettgehalt wurde in vivo ermittelt. Beide Cremes erhöhten nach 7 Tagen die Hautfeuchtigkeit signifikant. Eine signifikante höhere Hautfeuchtigkeit wurde in den Testarealen der NLC-haltigen Creme nach 28 und 42 Tagen gefunden

Selection and characterization of suitable lipid excipients for use in the manufacture of didanosine-loaded solid lipid nanoparticles and nanostructured lipid carriers

This research aimed to evaluate the suitability of lipids for the manufacture of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) loaded with the hydrophilic drug, didanosine (DDI). The crystalline state and polymorphism of lipids with the best‐solubulizing potential for DDI was investigated using differential scanning calorimetry (DSC) and wide‐angle X‐ray scattering (WAXS). DSC and WAXS were also used to determine potential interactions between the bulk lipids and DDI. Precirol® ATO 5 and Transcutol® HP showed the best‐solubilizing potential for DDI. Precirol® ATO 5 exists in the β‐modification before heating; however, a mixture of both α‐ and β‐modifications were detected following heating. Addition of Transcutol® HP to Precirol® ATO 5 changes the polymorphism of the latter from the β‐modification to a form that exhibits coexistence of the α‐ and β‐modifications. DDI exists in a crystalline state when dispersed at 5% (w/w) in Precirol® ATO 5 or in a Precirol® ATO 5/Transcutol® HP mixture. DSC and WAXS profiles of DDI/bulk lipids mixture obtained before and after exposure to heat revealed no interactions between DDI and the lipids. Precirol® ATO 5 and a mixture of Precirol® ATO 5 and Transcutol® HP may be used to manufacture DDI‐loaded SLN and NLC, respectively

In Vitro Characterisation of Vancomycin Loaded Glyceryl Monooleate-Water Liquid Crystalline Gel/Implants for Ocular Application

In the present investigation, vancomycin was incorporated in liquid crystalline gel made of glyceryl monooleate and water, with the aim to achieve a sustained-release and to deliver locally sufficient concentrations of vancomycin to the eye, improving its efficacy against bacterial infections [1–3]. [...