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Results for “drug release”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Studying the effect of drug-to-excipient ratio on drug release profile for drug coated balloons

Drug-coated balloons (DCB) have emerged as the alternative procedure for restenosis because of their ability to treat a variety of occlusion types with a uniform dose of anti-proliferative drugs. DCB are balloons coated with antiproliferative drugs encapsulated in a polymer matrix. There are several types of coating matrices used to produce DCB. In this study, the relationship between coating composition and drug release under physiologically relevant conditions was examined to understand how differences in coating composition impacts the drug transfer from the balloon surface to the simulated body fluids. To conduct the experiments, the balloons were coated with different paclitaxel (drug)-to-iopromide (excipient) ratios (3:1, 3:2 and 1:2) using an in-house developed micro-pipetting method. Scanning electron microscopy (SEM) images showed that the 3:1 PTX:IOP ratio produced a more uniform, crystalline microstructure with a thinner coating throughout the balloon surface compared to the other drug-to-excipient ratios. The 1:2 PTX:IOP ratio showed the least crystalline microstructure among the three ratios evaluated in this study. Three different drug elution conditions were tested. The amount of drug released to the medium was quantified by high performance liquid chromatography (HPLC). Our soaking study and submerge & deploy study showed that ~20% of the drug transferred to the target site under physiological conditions. A track and deploy method was performed using a “mock” artery, to simulate an in vitro environment. Coated balloons were passed through the mock artery to mimic tracking turns the balloon within the arteries during the angioplasty procedures. Seven elution samples were collected at different stages of the procedure. Finally, drug release results suggest that the higher excipient ratio helps to deliver the lipophilic drug to the target site under simulated conditions but causes higher drug loss during the balloon transfer process.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Preparation of pH ‐responsive cellulose nanofibril/sodium alginate based hydrogels for drug release

Abstract In this work, hydrogels composed of cellulose nanofibril (CNF) and sodium alginate (SA) were prepared as a pH‐responsive release system by controlling the amount of CNF and SA. Scanning electron microscopy, thermogravimetric analysis, and swelling rate methods were used to characterize. The results showed that when the mass ratio of CNF to SA was 2:1, CNF/SA hydrogels with better morphology were obtained. Due to the deprotonation or protonation of calcium alginate, as the pH changing from 1.5 to 11.0, the swelling ratio increased from 7 times to 19 times compared with its dry weight. The drug release behaviors of the CNF/SA hydrogels using ibuprofen (IBU) as a model drug were investigated in vitro. The release of IBU was faster in alkaline conditions and slower in acidic conditions. The drug release mechanism under pH stimulation could be interpreted by the Fickian diffusion and erosion effect based on Korsmeyer‐Peppas model.

Li, Yuhang↗
DOE OSTI2023

Orthogonal Gelations to Synthesize Core–Shell Hydrogels Loaded with Nanoemulsion‐Templated Drug Nanoparticles for Versatile Oral Drug Delivery

Hydrophobic active pharmaceutical ingredients (APIs) are ubiquitous in the drug development pipeline, but their poor bioavailability often prevents their translation into drug products. Industrial processes to formulate hydrophobic APIs are expensive, difficult to optimize, and not flexible enough to incorporate customizable drug release profiles into drug products. Here, a novel, dual-responsive gelation process that exploits orthogonal thermo-responsive and ion-responsive gelations is introduced. This one-step “dual gelation” synthesizes core–shell (methylcellulose-alginate) hydrogel particles and encapsulates drug-laden nanoemulsions in the hydrogel matrices. In situ crystallization templates drug nanocrystals inside the polymeric core, while a kinetically stable amorphous solid dispersion is templated in the shell. Drug release is explored as a function of particle geometry, and programmable release is demonstrated for various therapeutic applications including delayed pulsatile release and sequential release of a model fixed-dose combination drug product of ibuprofen and fenofibrate. Independent control over drug loading between the shell and the core is demonstrated. This formulation approach is shown to be a flexible process to develop drug products with biocompatible materials, facile synthesis, and precise drug release performance. This work suggests and applies a novel method to leverage orthogonal gel chemistries to generate functional core–shell hydrogel particles.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Effect of cholesterol on nano-structural alteration of light-activatable liposomes via laser irradiation: Small angle neutron scattering study

Although the light-activated liposomes have been extensively studied for drug delivery applications, the fundamental mechanism of the drug release based on lipid compositions has not been fully understood. Especially, despite the extensive use of cholesterol in the lipid composition, the role of cholesterol in the light-activated drug release has not been studied. Here, in this study, the influence of cholesterol on drug release from light-responsive drug-encapsulated liposomes after activated by near infrared (NIR) laser was investigated. We prepared methotrexate (MTX)-encapsulated DSPC liposomes consisting of 0 mol% (—Chol) or 35 mol% cholesterol (+Chol), with (+Au) or without gold nanorods (—Au) on the lipid bilayer to compare drug release, morphological changes, and nanostructures after laser irradiations. Transmission electron microscopy (TEM) and small angel neutron scattering (SANS) data revealed that only +Chol +Au liposomes showed partial aggregation of the liposomes after laser irradiation. Similar trends on the drug release and structural change were observed when the liposomes were heated to above chain-transition temperature. Overall, we have found that (1) inclusion of 35 mol% cholesterol enhanced the permeability of lipid bilayers above T c ; (2) the mechanism of laser-activated liposomal drug delivery is disrupting lipid bilayer membranes by the photothermal effect in the presence of plasmonic materials. By understanding the fundamentals of the technology, precise controlled drug release at a targeted site with great stability and repeatability is anticipated.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Controlling Drug Absorption, Release, and Erosion of Photopatterned Protein Engineered Hydrogels

A protein-engineered triblock copolymer hydrogel composed of two self-assembling domains (SADs) has been fabricated by a photoactivatable diazirine group followed by ultraviolet (UV)-mediated crosslinking. The photocrosslinkable protein polymer CEC-D has been patterned into various features including different micrometer-scale stripes by using lithographic techniques. The patterned hydrogels are important for encapsulation of small molecules where a photopatterned fraction of 50% is optimal for maximum absorption. Stripe-patterned CEC-D 100–100 exhibits slightly lower swelling ratios, an 8.9 times lower erosion profile, and a 2.6-fold higher drug release compared to the unpatterned hydrogel control, CEC-D0. Our studies demonstrate the potential of photocrosslinkable protein polymer hydrogels to be used as scaffolds for therapeutic delivery of small molecules. Furthermore, through photolithographic techniques on the protein hydrogel, a variety of functionalities can be achieved by patterning different features enabling the mimicry of biological systems.

77 NANOSCIENCE AND NANOTECHNOLOGY↗
DOE OSTI2020

Controlled release of entrapped nanoparticles from thermoresponsive hydrogels with tunable network characteristics

Thermoresponsive hydrogels have been studied intensively for creating smart drug carriers and controlled drug delivery. Understanding the drug release kinetics and corresponding transport mechanisms of nanoparticles (NPs) in a thermoresponsive hydrogel network is the key to the successful design of smart drug delivery systems. Here, we construct a mesoscopic model of rigid NPs entrapped in a hydrogel network in an aqueous solution, where the hydrogel network is formed by cross-linked semiflexible polymers of thermoresponsive poly(N-isopropylacrylamide) (PNIPAM). By varying the temperature crossing the lower critical solution temperature of PNIPAM, we can significantly change the hydrogel network characteristics. We systematically investigate how the matrix porosity and the nanoparticle size affect the transport kinetics of NPs at different temperatures. Quantitative results on the mean-squared displacement and the van Hove displacement distributions of NPs show that all NPs entrapped in the smart hydrogels undergo subdiffusion at both low and high temperatures. For a coil state, the transport of NPs in the hydrogels can be enhanced by decreasing the matrix porosity of the polymer network and NPs' size. However, when the solution temperature is increased above the critical temperature, the hydrogel network collapses following the coil-to-globule transition, with the NPs tightly trapped in some local regions inside the hydrogels. Consequently, the NP diffusion coefficient can be reduced by two orders of magnitude, or the diffusion processes can even be completely stopped. These findings provide new insights for designing controlled drug release from stimuli-responsive hydrogels, including autonomously switch on/off drug release in response to physical and chemical stimuli.

42 ENGINEERING↗
DOE OSTI2023

Metal–Organic Framework as a New Type of Magnetothermally‐Triggered On‐Demand Release Carrier

The development of external stimuli‐controlled payload systems has been sought after with increasing interest toward magnetothermally‐triggered drug release (MTDR) carriers due to their non‐invasive features. However, current MTDR carriers present several limitations, such as poor heating efficiency caused by the aggregation of iron oxide nanoparticles (IONPs) or the presence of antiferromagnetic phases which affect their efficiency. Herein, a novel MTDR carrier is developed using a controlled encapsulation method that fully fixes and confines IONPs of various sizes within the metal–organic frameworks (MOFs). This novel carrier preserves the MOF's morphology, porosity, and IONP segregation, while enhances heating efficiency through the oxidation of antiferromagnetic phases in IONPs during encapsulation. It also features a magnetothermally‐responsive nanobrush that is stimulated by an alternating magnetic field to enable on‐demand drug release. The novel carrier shows improved heating, which has potential applications as contrast agents and for combined chemo and magnetic hyperthermia therapy. It holds a great promise for magneto‐thermally modulated drug dosing at tumor sites, making it an exciting avenue for cancer treatment.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Global harmonization of immediate‐release solid oral drug product bioequivalence recommendations and the impact on generic drug development

Immediate-release (IR) solid oral drug products constitute a significant portion of approved drug products and products under development. Bioequivalence (BE) assessment for these oral products is important for establishing therapeutic equivalence for generic products to their respective comparator products. In December 2022, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) published the first new draft guideline on BE for IR solid oral dosage forms (M13A). To support the development of ICH M13A, we comprehensively reviewed the landscape of oral IR products approved by the U.S. Food and Drug Administration (FDA) and compared BE recommendations for these products in the current U.S. FDA and European Medicines Agency (EMA) BE guidances. We utilized databases including Drugs@FDA, Orange Book, and product-specific guidances (PSGs) published on the U.S. FDA and EMA websites to collect information. Oral IR products account for 46% of all FDA-approved new drug applications currently listed in Orange Book with 82.5% solids, 0.9% semi-solids, and 16.6% liquids. For all published U.S. FDA PSGs for solid oral IR products, in vivo BE studies with pharmacokinetic (PK) endpoints account for 88% of BE approaches recommended. Of these PK BE studies, 86.5% recommended fasting and fed BE studies, while only 15.9% EMA PSGs recommended both fasting and fed BE studies. This review helps clarify the scope of U.S. solid oral IR products impacted by the new ICH M13A draft guideline and demonstrates how recommendations in draft ICH M13A could significantly harmonize BE recommendations for IR oral products to facilitate global drug development.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Switching from batch to continuous granulation: A case study of metoprolol succinate ER tablets

Continuous manufacturing (CM) has been used to produce several immediate release drug products. No extended-release (ER) product manufactured employing CM technology has been approved yet. Herein this study investigated the critical aspects of switching from the batch mode of high shear granulation to the continuous operation of twin-screw granulation for extended-release tablets. Metoprolol succinate ER tablets was used as a model ER formulation for this purpose. A central composite design (CCD) was employed to determine the effects of high shear granulator (HSG) parameters, namely impeller speed, granulation time, and binder liquid feeding rate, on the critical granulation characteristics important for product performance. These critical granulation characteristics served as a guide for switching from the batch processing to the continuous operation for achieving the same breaking strength and dissolution for this ER metoprolol tablets. The granulation time was the most critical factor affecting the bulk properties of granules which contributed to tablet dissolution. The higher density and lower compressibility of granules were attained at the longest granulation time of 5.4 min with the fastest liquid feeding rate of 75 g/min. The granules’ density was the primary factor negatively affecting the dissolution of metoprolol tablets. However, the breaking strength of tablets confounded the effect of granules density on metoprolol dissolution. Switching the processing parameters of high shear granulation to twin-screw granulation achieved similar dissolution profiles (F2 greater than 50). The screw speed was not found to affect bulk properties of granules. The root cause of granulation failures in twin-screw granulation, such as premature consolidation, excessive swelling, poor cohesion, inconsistent shearing effects, and formation of deformed agglomerates, were identified. In conclusion, the use of critical granulation characteristics through a performance-based approach of ER tablets facilitated the switching of manufacturing of an ER formulation form batch to continuous operation.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

Hot-melt extrudability of amorphous solid dispersions of flubendazole-copovidone: An exploratory study of the effect of drug loading and the balance of adjuvants on extrudability and dissolution

The FDA-approved anthelmintic flubendazole has shown potential to be repositioned to treat cancer and dry macular degeneration; however, its poor water solubility limits its use. Amorphous solid dispersions may overcome this challenge, but the balance of excipients may impact the preparation method and drug release. Here, we evaluate the influence of adjuvants and drug loading on the development of an amorphous solid dispersion of flubendazole-copovidone by hot-melt extrusion. The drug, copovidone, and adjuvants (magnesium stearate and hydroxypropyl cellulose) mixtures were statistically designed, and the process was performed in a twin-screw extruder. The study showed that flubendazole and copovidone mixtures were highly extrudable, except when drug loading was high (>40%). Furthermore, magnesium stearate positively impacted the extrusion and was more effective than hydroxypropyl cellulose. The extruded materials were evaluated by modulated differential scanning calorimetry and X-ray powder diffraction, obtaining positive amorphization and physical stability results. Pair distribution function analysis indicated the presence of drug rich domains with medium-range order structure and no evidence of polymer-drug interaction. All extrudates presented faster dissolution (HCl, pH 1.2) than pure flubendazole, and both adjuvants had a notable influence on the dissolution rate. In conclusion, hot-melt extrusion may be a viable option to obtain stable flubendazole: copovidone amorphous dispersions.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Crystalline Loading of Lipophilic Coenzyme Q10 Pharmaceuticals within Conjugated Carbon Aerogel Derivatives

Low-density aerogel materials currently are being considered for applications in controlling the rate of release for small-molecule pharmaceuticals in vivo. In particular, silica (SiO2) aerogels are an intriguing platform for controlling both the absolute amount of drug loading, but also the crystalline state of small molecule pharmaceuticals has been shown to affect drug release kinetics. To date, loading silica aerogel materials with crystalline pharmaceuticals typically require dissolving small molecules in a supercritical solvent (i.e., CO2) before drying to recover the aerogel/drug composite. Here we demonstrate a simple and low-cost method for controlling the crystallinity of the model drug coenzyme Q10 (CoQ10) within carbon aerogel materials by rationally controlling the chemical microstructure of the aerogel to exhibit ?-conjugated (sp2) chemical bonding. In particular, both pyrolyzed graphene and nanodiamond aerogels exhibit enhanced intrinsic drug loading capacity and CoQ10 crystallinity over a broad range of sp2 surface-curvature. In contrast, amorphous carbon aerogel materials are observed to load CoQ10 pharmaceuticals with strictly amorphous microstructure.

Lim, Mathew↗
DOE OSTI2023

Biological toxicity and environmental hazards associated with PLGA nanoparticles

There have been tremendous advances in nanotechnology. More recently, the use of nanoparticles has expanded to applications including materials, packaging, energy, and medical uses such as drug delivery, diagnostics, and therapeutics. The American Society for Testing and Materials (ASTM) and the International Organization for Standardization (ISO) define nanoparticles as particles with at least one dimension measuring between 1 and 100 nm (2), but this view is generally too limited, and recommendations have been made to consider all materials with a dimension measuring under 1,000 nm as nanoparticles. The biomedical uses of nanoparticles are particularly promising because of their ability to reach and target various sites and organs. However, some nanoparticles can be composed of toxic materials or are limited by issues of biodistribution and bioaccumulation, which have hampered their use in biomedicine. The copolymer poly lactic-co-glycolic acid (PLGA) has gained use in biomedical applications as a delivery system because it is considered biocompatible and can be formulated with controlled degradation in physiological environments. PLGA has a history in biomedicine that dates to the 1970s when biodegradable sutures were developed using PLGA. In addition, the United States (US) Food and Drug Administration (FDA) and the European Medicine Agency (EMA) have approved various PLGA particle formulations as therapeutic delivery vehicles. Interest in biocompatible materials to deliver a range of therapeutic drugs, proteins, nucleic acids, and other molecules has risen recently. In addition to drug delivery, sustained drug release can be achieved by tuning the physical properties of PLGA, such as the molecular weight, ratio of lactic to glycolic acid, drug concentration, stabilizing molecules, and particle size. Given the rise of nanoparticles, human and environmental exposure to them is inevitable as more applications use free, unbound, and highly mobile particles. Although PLGA is generally considered safe, a detailed understanding of how PLGA and the other components used to help formulate this copolymer into a nanoparticle delivery vehicle is useful for assessing potential harmful effects. Despite recent advances in PLGA nanoparticle formulations, residual stabilizing molecules, inconsistent preparations, and batch-to-batch variations can lead to toxicity. Poor preparations of PLGA can lead to common mechanisms of toxicity observed with nanoparticles, such as inflammation and oxidative stress. Consistency in PLGA formulations and accurate methods to evaluate nanoparticle toxicity are needed to ensure safety. In order to better assess PLGA nanoparticles as non-toxic delivery systems, it is critical to understand their physical and chemical properties and the formulation protocols that may introduce toxic components into particles.

Biology, nanoparticle, toxicity↗
DOE OSTI2020

Biomedical Integration of Metal–Organic Frameworks

Metal–organic frameworks (MOFs) have recently been demonstrated to be excellent platforms for biomedical applications. On account of their porous nature and modular structure, MOFs have served as bioactive-compound carriers, cell-imaging materials, and therapeutic agents. MOF cavities allow the encapsulation of a variety of guest molecules, facilitating controllable drug release and optical imaging. The metal components of MOFs make them suitable for magnetic resonance imaging (MRI) and computed tomography (CT). Further, MOF-embedded therapeutic agents have demonstrated promise in photodynamic and photothermal therapies. In this review, we describe several advanced examples that utilize MOFs in these cutting-edge applications. Investigation of the relationship between their structure and designated application will enable future, informed exploration of MOFs for biomedical applications.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗