19 research outputs found
Beta-cyclodextrin Conjugated Magnetic Nanoparticles for Bio-and Environmental Applications
Ph.DDOCTOR OF PHILOSOPH
Core-shell composite hydrogels for the controlled formation and release of nanocrystals of poorly soluble active pharmaceutical ingredient
Although roughly 40% of pharmaceuticals being developed are poorly water-soluble, this major class of drugs still lacks a formulation strategy capable of producing high loads, fast release kinetics, and low energy input. The development of such innovative biocompatible materials has been a major focus of pharmaceutical materials research. In this work, we develop a novel bottom-up approach for producing and formulating nanocrystals of poorly water-soluble active pharmaceutical ingredients (APIs) using core-shell composite hydrogel beads. We show that the API dissolution profile can be modulated by accurately controlling crystal size and loading and shell thickness. Organic phase nanoemulsions stabilized by polyvinyl alcohol (PVA) and containing a model hydrophobic API (fenofibrate) are embedded in the alginate hydrogel matrix and subsequently act as crystallization reactors. Controlled evaporation of this composite material produces core-shell structured alginate-PVA hydrogels with drug nanocrystals ranging from 500 nm to 650 nm embedded within the core. Adjustable loading of API nanocrystals up to 83% by weight is achieved. Our drug nanocrystal-formulated hydrogels exhibit improved solubility and dissolution rates comparable to commercial dissolution. We also demonstrate that the drug release patterns of the fenofibrate nanocrystals contained in the core can be modulated by altering the thickness of PVA shell of the composite hydrogels. The thickness of the polymer shell of the composite hydrogels can be engineered either by varying the volume fraction of organic phase or by changing the overall core-shell particle size. Thus, these composite materials offer a ‘designer’ drug delivery system by offering a controlled dissolution rate and lag time. Overall, our approach enables a novel means of simultaneous controlled crystallization and formulation of poorly soluble drugs that circumvents energy intensive top-down processes in traditional manufacturing.
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Polymers for Extrusion‐Based 3D Printing of Pharmaceuticals: A Holistic Materials–Process Perspective
Three dimensional (3D) printing as an advanced manufacturing technology is progressing to be established in the pharmaceutical industry to overcome the traditional manufacturing regime of ʹone size fits for allʹ. Using 3D printing, it is possible to design and develop complex dosage forms that can be suitable for tuning drug release. Polymers are the key materials that are necessary for 3D printing. Among all 3D printing processes, extrusion‐based (both fused deposition modeling (FDM) and pressure‐assisted microsyringe (PAM)) 3D printing is well researched for pharmaceutical manufacturing. It is important to understand which polymers are suitable for extrusion‐based 3D printing of pharmaceuticals and how their properties, as well as the behavior of polymer–active pharmaceutical ingredient (API) combinations, impact the printing process. Especially, understanding the rheology of the polymer and API–polymer mixtures is necessary for successful 3D printing of dosage forms or printed structures. This review has summarized a holistic materials–process perspective for polymers on extrusion‐based 3D printing. The main focus herein will be both FDM and PAM 3D printing processes. It elaborates the discussion on the comparison of 3D printing with the traditional direct compression process, the necessity of rheology, and the characterization techniques required for the printed structure, drug, and excipients. The current technological challenges, regulatory aspects, and the direction toward which the technology is moving, especially for personalized pharmaceuticals and multi‐drug printing, are also briefly discussed
A General Route for Nanoemulsion Synthesis Using Low-Energy Methods at Constant Temperature
© 2017 American Chemical Society. The central dogma of nanoemulsion formation using low-energy methods at constant temperature - popularly known as the emulsion inversion point (EIP) method - is that to create O/W nanoemulsions, water should be added to a mixture of an oil and surfactant. Here, we demonstrate that the above order of mixing is not universal and a reverse order of mixing could be superior, depending on the choice of surfactant and liquid phases. We propose a more general methodology to make O/W as well as W/O nanoemulsions by studying the variation of droplet size with the surfactant hydrophilic-lypophilic balance for several model systems. Our analysis shows that surfactant migration from the initial phase to the interface is the critical step for successful nanoemulsion synthesis of both O/W and W/O nanoemulsions. On the basis of our understanding and experimental results, we utilize the reverse order of mixing for two applications: (1) crystallization and formulation of pharmaceutical drugs with faster dissolution rates and (2) synthesis of alginate-based nanogels. The general route provides insights into nanoemulsion formation through low-energy methods and also opens up possibilities that were previously overlooked in the field
Polymers for Extrusion-Based 3D Printing of Pharmaceuticals: A Holistic Materials–Process Perspective
Three dimensional (3D) printing as an advanced manufacturing technology is progressing to be established in the pharmaceutical industry to overcome the traditional manufacturing regime of \u27one size fits for all\u27. Using 3D printing, it is possible to design and develop complex dosage forms that can be suitable for tuning drug release. Polymers are the key materials that are necessary for 3D printing. Among all 3D printing processes, extrusion-based (both fused deposition modeling (FDM) and pressure-assisted microsyringe (PAM)) 3D printing is well researched for pharmaceutical manufacturing. It is important to understand which polymers are suitable for extrusion-based 3D printing of pharmaceuticals and how their properties, as well as the behavior of polymer–active pharmaceutical ingredient (API) combinations, impact the printing process. Especially, understanding the rheology of the polymer and API–polymer mixtures is necessary for successful 3D printing of dosage forms or printed structures. This review has summarized a holistic materials–process perspective for polymers on extrusion-based 3D printing. The main focus herein will be both FDM and PAM 3D printing processes. It elaborates the discussion on the comparison of 3D printing with the traditional direct compression process, the necessity of rheology, and the characterization techniques required for the printed structure, drug, and excipients. The current technological challenges, regulatory aspects, and the direction toward which the technology is moving, especially for personalized pharmaceuticals and multi-drug printing, are also briefly discussed
Environmentally Friendly β‑Cyclodextrin–Ionic Liquid Polyurethane-Modified Magnetic Sorbent for the Removal of PFOA, PFOS, and Cr(VI) from Water
Emerging
contaminants such as perfluorinated compounds (PFCs) and
heavy metals are of increasing concerns due to their detrimental effects
on environment and human health. Their mixtures are often present
at contaminated sites that pose a challenge in water remediation.
Herein, we report a multifunctional magnetic sorbent (Fe<sub>3</sub>O<sub>4</sub>-CDI-IL MNPs) that was prepared by modifying the magnetic
Fe<sub>3</sub>O<sub>4</sub> nanoparticle with β<i>-</i>cyclodextrin–ionic liquid (β<i>-</i>CD-IL)
polyurethanes for the removal of perfluorooctanesulfonate (PFOS),
perfluorooctanoic acid (PFOA), and Cr(VI) from aqueous solution. The
successful grafting of the β<i>-</i>CD-IL polymer
on magnetic nanoparticles was confirmed by FTIR, ζ -potential,
TGA, and VSM. The sorption behaviors of Fe<sub>3</sub>O<sub>4</sub>-CDI-IL MNPs were investigated in terms of sorption kinetics, isotherms,
simultaneous removal capability, and reusability. The kinetic results
showed that the sorption of PFOS, PFOA, and Cr(VI) reached equilibrium
within 4, 6, and 3 h, respectively, and the pseudo-second-order kinetic
model best described the kinetic data. The solution pH had more obvious
effects on the sorption of PFOA and Cr(VI) than that of PFOS. The
coupling of ionic liquid with the β<i>-</i>CD polymer
backbone could significantly enhance the removal efficiencies of both
PFOS and PFOA. The sorption isotherms indicated that the heterogeneous
sorption capacities of Fe<sub>3</sub>O<sub>4</sub>-CDI-IL MNPs were
13,200 and 2500 μg/g for PFOS and PFOA, respectively, and the
monolayer sorption capacity was 2600 μg/g for Cr(VI) ions. The
Cr(VI)-PFC binary sorption experiments exhibited a decrease in sorption
capacities for PFCs, but the removal of Cr(VI) was unaffected with
the introduction of PFCs as co-contaminants. The hydrophobic interactions
and electrostatic attraction were mainly involved in the PFC sorption
process, whereas the ion exchange and reduction was responsible for
Cr(VI) sorption. In addition, Fe<sub>3</sub>O<sub>4</sub>-CDI-IL MNPs
could be readily recovered with a permanent magnet, regenerated, and
reused at least 10 times without any significant efficiency loss.
This multifunctional sorbent thus shows potential in the removal of
coexisting toxic contaminants from water or wastewater
Thermoresponsive nanoemulsion-based gel synthesized through a low-energy process
© 2019, The Author(s). Thermoresponsive nanoemulsions find utility in applications ranging from food to pharmaceuticals to consumer products. Prior systems have found limited translation to applications due to cytotoxicity of the compositions and/or difficulties in scaling-up the process. Here, we report a route to thermally gel an oil-in-water nanoemulsion using a small amount of FDA-approved amphiphilic triblock Pluronic copolymers which act as gelling agents. At ambient temperature the suspension displays liquid-like behavior, and quickly becomes an elastic gel at elevated temperatures. We propose a gelation mechanism triggered by synergistic action of thermally-induced adsorption of Pluronic copolymers onto the droplet interface and an increased micelle concentration in the aqueous solution. We demonstrate that the system’s properties can be tuned via many factors and report their rheological properties. The nanoemulsions are prepared using a low-energy process which offers an efficient route to scale-up. The nanoemulsion formulations are well-suited for use in cosmetics and pharmaceutical applications
Nano-vesicle based anti-fungal formulation shows higher stability, skin diffusion, biosafety and anti- fungal efficacy in vitro
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Opportunistic fungal infections are responsible for over 1.5 million deaths per year. This has created a need for highly effective antifungal medication to be as potent as possible. In this study, we improved the efficacy of a common over the counter (OTC) antifungal skin medication, miconazole, by encapsulating nano-molecules of the drug in cholesterol/sodium oleate nano-vesicles. These nano-vesicles were characterized to optimize their size, zeta potential, polydispersity index and encapsulation efficiency. Furthermore, these nano-vesicles were compared to a conventional miconazole-based commercially available cream to determine potential improvements via permeation through the stratum corneum, cytotoxicity, and antifungal capabilities. Our results found that the vesicle size was within the nano range (~300 nm), with moderate polydispersity and stability. When compared with the commercially available cream, Actavis, as well as free miconazole, the miconazole nano-vesicle formulation displayed enhanced fungal inhibition by a factor of three or more when compared to free miconazole. Furthermore, with smaller nanoparticle (NP) sizes, higher percentages of miconazole may be delivered, further enhancing the efficacy of miconazole’s antifungal capability. Cytotoxicity studies conducted with human dermal fibroblast cells confirm its biosafety and biocompatibility, as cell survival rate was observed to be twofold higher in nano-vesicle formulation than free miconazole. This formulation has the potential to treat fungal infections through increasing the retention time in the skin, improving the treatment approach, and by enhancing the efficacy via the use of nano-vesicles
Functionalized Silica Nanoparticles as Additives for Polymorphic Control in Emulsion-Based Crystallization of Glycine
Emulsion-based crystallization to produce spherical crystalline
agglomerates is an attractive route to control the size and morphology
of active pharmaceutical ingredient (API) crystals, which in turn
improves downstream processability. Here, we demonstrate the use of
silica nanoparticles modified with different surface functional groups
(hydroxyl, amino, carboxylic, imidazolim chloride, and chloride) as
additives in water-in-oil emulsion-based crystallization of glycine,
a model API molecule. Spherical agglomerates of glycine obtained under
different experimental conditions are characterized by powder X-ray
diffraction (XRD) and scanning electron microscopy. Our observations
reveal the strong influence of particle functionalization on polymorphic
outcome at near-neutral (pH ∼6) conditions, where we are able
to selectively crystallize the least stable β-polymorph of glycine
or tune the relative ratio of α- and β-polymorphs by selecting
appropriate experimental conditions. Mixtures of α- and γ-glycine
are typically obtained under acidic solutions (pH ∼3), irrespective
of the functional groups used. We examine the influence of charge
and immobilization density of surface functional groups and nanoparticle
concentration on the polymorphic outcome and rationalize our results
by analyzing molecular and functional group speciation