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Drug Delivery and Translational Research Feb 2024Oral administration is the most commonly used form of treatment due to its advantages, including high patient compliance, convenient administration, and minimal... (Review)
Review
Oral administration is the most commonly used form of treatment due to its advantages, including high patient compliance, convenient administration, and minimal preparation required. However, the traditional preparation process of oral solid preparation has many defects. Although continuous manufacturing line that combined all the unit operations has been developed and preliminarily applied in the pharmaceutical industry, most of the currently used manufacturing processes are still complicated and discontinuous. As a result, these complex production steps will lead to low production efficiency and high quality control risk of the final product. Additionally, the large-scale production mode is inappropriate for the personalized medicines, which commonly is customized with small amount. Several attractive techniques, such as hot-melt extrusion, fluidized bed pelletizing and spray drying, could effectively shorten the process flow, but still, they have inherent limitations that are challenging to address. As a novel manufacturing technique, 3D printing could greatly reduce or eliminate these disadvantages mentioned above, and could realize a desirable continuous production for small-scale personalized manufacturing. In recent years, due to the participation of 3D printing, the development of printed drugs has progressed by leaps and bounds, especially in the design of oral drug dosage forms. This review attempts to summarize the new development of 3D printing technology in oral preparation and also discusses their advantages and disadvantages as well as potential applications.
Topics: Humans; Technology, Pharmaceutical; Drug Industry; Pharmaceutical Preparations; Administration, Oral; Printing, Three-Dimensional
PubMed: 37620647
DOI: 10.1007/s13346-023-01414-8 -
BMJ Open Ophthalmology Aug 2023To evaluate effectiveness of dexamethasone intravitreal implant 0.7 mg (DEX) monotherapy in the AUSSIEDEX study non-responder subgroup, defined by diabetic macular... (Observational Study)
Observational Study
AIM
To evaluate effectiveness of dexamethasone intravitreal implant 0.7 mg (DEX) monotherapy in the AUSSIEDEX study non-responder subgroup, defined by diabetic macular oedema (DME) refractory to anti-vascular endothelial growth factor (anti-VEGF) agents.
METHODS
This prospective, open-label, observational, real-world study included pseudophakic and phakic (scheduled for cataract surgery) eyes that did not achieve a ≥5-letter best corrected visual acuity (BCVA) gain and/or clinically significant central subfield retinal thickness (CRT) improvement after 3-6 anti-VEGF injections for DME (N=143 eyes), regardless of baseline BCVA and CRT. After an initial DEX injection (baseline visit), reinjection was permitted at ≥16-week intervals.
PRIMARY ENDPOINTS
changes in mean BCVA and CRT from baseline to week 52. Safety assessments included adverse events.
RESULTS
Of 143 eyes, 53 (37.1%) and 89 (62.2%) switched to DEX after 3-6 (early) and >6 (late) anti-VEGF injections, respectively; 1 (0.7%) had missing information. With 2.3 injections (mean) over 52 weeks, the change in mean BCVA from a baseline of 57.8 letters was not significant at week 52. Mean CRT improved significantly from a baseline of 417.8 μm at week 52 (mean change -60.9 μm; p<0.001). Outcomes were similar in eyes switched to DEX early and late. No unexpected adverse events were reported; no filtration surgeries were required.
CONCLUSION
To date, AUSSIEDEX is the largest prospective, real-world study of DEX monotherapy for treatment-naïve or anti-VEGF-refractory DME. Following early or late switch from anti-VEGF agents, DEX significantly improved anatomic outcomes at 52 weeks without new safety concerns, supporting use in anti-VEGF-refractory DME.
TRIAL REGISTRATION NUMBER
NCT02731911.
Topics: Humans; Macular Edema; Glucocorticoids; Dexamethasone; Prospective Studies; Vascular Endothelial Growth Factor A; Drug Implants; Intravitreal Injections; Diabetic Retinopathy; Vascular Endothelial Growth Factors; Diabetes Mellitus
PubMed: 37541745
DOI: 10.1136/bmjophth-2022-001224 -
Journal of Neuroscience Methods Jun 2024The neuronal and gliaI populations within the brain are tightly interwoven, making isolation and study of large populations of a single cell type from brain tissue a...
BACKGROUND
The neuronal and gliaI populations within the brain are tightly interwoven, making isolation and study of large populations of a single cell type from brain tissue a major technical challenge. Concurrently, cell-type specific extracellular vesicles (EVs) hold enormous diagnostic and therapeutic potential in neurodegenerative disorders including Alzheimer's disease (AD).
NEW METHOD
Postmortem AD cortical samples were thawed and gently dissociated. Following filtration, myelin and red blood cell removal, cell pellets were immunolabeled with fluorescent antibodies and analyzed by flow cytometry. The cell pellet supernatant was applied to a triple sucrose cushion for brain EV isolation.
RESULTS
Neuronal, astrocyte and microglial cell populations were identified. Cell integrity was demonstrated using calcein AM, which is retained by cells with esterase activity and an intact membrane. For some experiments cell pellets were fixed, permeabilized, and immunolabeled for cell-specific markers. Characterization of brain small EV fractions showed the expected size, depletion of EV negative markers, and enrichment in positive and cell-type specific markers.
COMPARISON WITH EXISTING METHODS AND CONCLUSIONS
We optimized and integrated established protocols, aiming to maximize information obtained from each human autopsy brain sample. The uniqueness of our method lies in its capability to isolate cells and EVs from a single cryopreserved brain sample. Our results not only demonstrate the feasibility of isolating specific brain cell subpopulations for RNA-seq but also validate these subpopulations at the protein level. The accelerated study of EVs from human samples is crucial for a better understanding of their contribution to neuron/glial crosstalk and disease progression.
Topics: Alzheimer Disease; Extracellular Vesicles; Cell Separation; Cerebral Cortex; Humans; Cryopreservation; Autopsy; RNA-Seq; Neuroglia; Neurons
PubMed: 38626853
DOI: 10.1016/j.jneumeth.2024.110137 -
Tropical Animal Health and Production Mar 2024Phytonutrients (PTN) namely saponins (SP) and condensed tannins (CT) have been demonstrated to assess the effect of rumen fermentation and methane mitigation....
Combination effects of phytonutrient pellet and lemongrass (Cymbopogon citratus) powder on rumen fermentation efficiency and nutrient degradability using in vitro technique.
Phytonutrients (PTN) namely saponins (SP) and condensed tannins (CT) have been demonstrated to assess the effect of rumen fermentation and methane mitigation. Phytonutrient pellet containing mangosteen, rambutan, and banana flower (MARABAC) and lemongrass including PTN, hence these plant-phytonutrients supplementation could be an alternative plant with a positive effect on rumen fermentation. The aim of this experiment was to evaluate the effect of supplementation of MARABAC and lemongrass (Cymbopogon citratus) powder on in vitro fermentation modulation and the ability to mitigate methane production. The treatments were arranged according to a 3 × 3 Factorial arrangement in a completely randomized design. The two experimental factors consisted of MARABAC pellet levels (0%, 1%, and 2% of the total substrate) and lemongrass supplementation levels (0%, 1%, and 2% of the total substrate). The results of this study revealed that supplementation with MARABAC pellet and lemongrass powder significantly improved gas production kinetics (P < 0.01) and rumen fermentation end-products especially the propionate production (P < 0.01). While rumen methane production was subsequently reduced by both factors. Additionally, the in vitro dry matter degradability (IVDMD) and organic matter degradability (IVOMD) were greatly improved (P < 0.05) by the respective treatments. MARABAC pellet and lemongrass powder combination showed effective methane mitigation by enhancing rumen fermentation end-products especially the propionate concentration and both the IVDMD and IVOMD, while mitigated methane production. The combined level of both sources at 2% MARABAC pellet and 2% lemongrass powder of total substrates offered the best results. Therefore, MARABAC pellet and lemongrass powder supplementation could be used as an alternative source of phytonutrient in dietary ruminant.
Topics: Animals; Cymbopogon; Dietary Supplements; Fermentation; In Vitro Techniques; Methane; Nutrients; Phytochemicals; Powders; Propionates; Rumen
PubMed: 38453787
DOI: 10.1007/s11250-024-03936-w -
Saudi Pharmaceutical Journal : SPJ :... Aug 2023Lisinopril (LIS) is antihypertensive drug, classified as a class III drug with high water solubility and low permeability. To overcome the low permeability, 3 factorial...
Lisinopril (LIS) is antihypertensive drug, classified as a class III drug with high water solubility and low permeability. To overcome the low permeability, 3 factorial designs aimed to formulate LIS as a sustained-release (LIS-SR) matrix pellet by extrusion/spheronization. Matrix pellets were composed of wet mass containing Avicel® and polymeric matrix polymers (sodium alginate (SA) and chitosan (CS)). Evaluation of the effect of two independent variables, matrix-forming units (SA and CS) on mean line torque, on pellet size, dissolution rate after 6 h, and mucoadhesion strength of the pellets were assessed using Statgraphics software. The tested formulations (F1-F9) showed that mean line torque ranged from 1.583 to 0.461 Nm, with LIS content in the LIS-SR pellets ranged from 87.9 to 103%, sizes varied from 1906 to 1404 µm and high percentages of drug released from pellets formulations (68.48 to 74.18 %), while the mean zeta potential value of mucoadhesive range from -17.5 to -22.9 mV. The selection of optimized formulation must have the following desirability: maximum peak torque, maximum pellets' particle size, and minimum % LIS release after 6hr. LIS optimized sustained release pellet formula composed of 2,159 % SA and 0.357 % CS was chosen as optimized formula. It's showed a 1.055 Nm mean line torque was responsible for the increased pellet size to 1830.8 μm with decreased release rate 56.2 % after 6 hr, and -20.33 mV average mucin zeta potential. mucoadhesion studies revealed that that the optimize formulation, exhibited excellent mucoadhesive properties, after 1 h, about 73% of the pellets were still attached to the mucus membrane. Additionally, permeation determination of LIS from the optimized LIS-SR formulation was found to be significantly higher (1.7-folds) as compared to free LIS. In conclusion: LIS-SR matrix pellets, prepared with an extrusion/spheronization have desirable excellent characteristics sustained-release pellet formulation of LIS-SR was able to sustain the release of LIS for up to 8 h.
PubMed: 37457369
DOI: 10.1016/j.jsps.2023.06.023 -
International Journal of Pharmaceutics Aug 2023Pellet coat damage in multi-unit pellet system (MUPS) tablets has previously been studied and addressed with limited success. The effects of lactose filler material...
Pellet coat damage in multi-unit pellet system (MUPS) tablets has previously been studied and addressed with limited success. The effects of lactose filler material attributes on pellet coat damage have been relatively well-studied but a similar understanding of microcrystalline cellulose (MCC) is lacking notwithstanding its high cushioning potential. Hence, the relationships between MCC attributes and pellet coat damage were investigated. Single pellet in minitablets (SPIMs) were used to isolate pellet-filler effects and reveal the under-unexplored impact of risk factors found in MUPS tablets. MUPS tablets and SPIMs were prepared with various grades of MCC and pellets with an ethylcellulose or acrylic coat at various compaction pressures. Subsequently, the extent of pellet coat damage was determined by dissolution test and quantified using two indicators to differentiate the nature of the damage. A multi-faceted analytical approach incorporated linear regression, correlations and a classification and regression tree algorithm and evaluated how MCC attributes, such as flowability, particle size and plastic deformability, exert various influences on the extent of ethylcellulose and acrylic pellet coat damage. This analysis improved the understanding of the different mechanisms by which pellet coat damage to these two polymer types occurs which can help enhance future pellet coat damage mitigation strategies.
Topics: Drug Implants; Excipients; Tablets; Lactose; Particle Size
PubMed: 37467819
DOI: 10.1016/j.ijpharm.2023.123245 -
The European Journal of Contraception &... Jun 2024Migration is a rare but serious complication of the etonogestrel contraceptive implant, and little is known about its extent. (Review)
Review
INTRODUCTION
Migration is a rare but serious complication of the etonogestrel contraceptive implant, and little is known about its extent.
PURPOSE
To document and characterise cases of etonogestrel contraceptive implant migration in the scientific literature.
METHODS
A systematic review of Medline, Embase and Global Health databases was carried out between January 2000 and January 2023 to identify articles presenting implant migrations. Narrative reviews, conference abstracts and articles not written in English or French were excluded.
RESULTS
Forty-five articles, mostly published since 2016, were identified (eight case series and 37 case reports), for a total of 148 independent cases of migration: in pulmonary blood vessels ( = 74), in non-pulmonary blood vessels ( = 16) and extravascular ( = 58). Many patients are asymptomatic and migration is often an incidental finding. A non-palpable implant and symptoms related to implant location (intra- or extra-vascular) may be indicative of migration. Inadequate insertion and normal or underweight appear to increase the risk of migration. Scientific societies and authors offer practical strategies to deal with implant migration.
CONCLUSION
Professionals who insert and remove contraceptive implants must be adequately trained. They need to be on the lookout for implant migration, and promptly refer patients to appropriate care if migration is suspected.
Topics: Humans; Desogestrel; Foreign-Body Migration; Female; Drug Implants; Contraceptive Agents, Female; Device Removal; Contraceptive Agents, Hormonal
PubMed: 38712717
DOI: 10.1080/13625187.2024.2342919 -
Dalton Transactions (Cambridge, England... Nov 2023Magnetic nanoarchitectures have been used to introduce multifunctionality in biopolymeric matrices. Bionanocomposite foams based on the corn protein zein were prepared...
Magnetic nanoarchitectures have been used to introduce multifunctionality in biopolymeric matrices. Bionanocomposite foams based on the corn protein zein were prepared for the first time using the hydrophobic properties of zein in a sequential treatment consisting of the removal of ethanol-soluble fractions, followed by the water swelling of the remaining phase and a further freeze-drying process. When this protocol is applied to zein pellets, they can be consolidated as porous monoliths. Moreover, it is possible to incorporate diverse types of inorganic nanoparticles in the starting pellet to produce the bionanocomposite foams. In particular, the preparation of superparamagnetic foams has been explored using two approaches: the direct incorporation of magnetite nanoparticles in a ferrofluid by impregnation in the foams, and the application of the foaming process to mixtures of zein with magnetite nanoparticles alone or previously assembled into sepiolite clay fibers. The first methodology leads to the production of inhomogeneous foams, while the use of magnetite nanoparticles and better FeO-sepiolite nanoarchitectured materials as fillers results in more homogeneous materials with improved water stability and mechanical properties, offering superparamagnetic behavior. The resulting multifunctional foams have been tested in adsorption processes using the herbicide 4-chloro-2-methylphenoxyacetic acid as a model pollutant, confirming their potential utility in decontamination applications in open waters as they can be easily recovered from the aqueous medium using a magnet.
PubMed: 37930107
DOI: 10.1039/d3dt02845c -
Journal of the Mechanical Behavior of... Dec 2023Hydroxyapatite (HAp) exists as an inorganic and crystalline composition present in bones and dental enamel, and hence can be utilized as a direct element or as part of...
Hydroxyapatite (HAp) exists as an inorganic and crystalline composition present in bones and dental enamel, and hence can be utilized as a direct element or as part of the composition of biomaterials and implants for dental and orthopaedic applications. Listed below are a few synthesis techniques for HAp that are listed in the literature: solid-state and mechano-chemical methods (dry methods), wet chemical precipitation and sol-gel methods (wet methods), and combustion and pyrolysis methods (high-temperature processes). Nevertheless, there are new and more productive techniques that result in HAp with a regulated morphology, such as the Schiff base method, which, on reaction with calcium and phosphate precursors, forms chelating complexes to produce HAp nuclei. This research paper presents the comparison in characteristics between HAp synthesized using Schiff base (HAp-SB), wet chemical precipitation (HAp-WC) methods, and commercial HAp (HAp-CM) in their powdered and pelleted form. The average size of HAp-WC particles in the spherical form was found to be 603 nm ± 176, HAp-SB were found to have rod-like morphology, which is very similar to human bone-like HAp, with an average length and width of 1522 nm ± 759 and 400 nm ± 112, respectively, and HAp-CM were found to have spherical morphology with dimensions of 52 nm ± 25. Biological studies show that cell viability of HAp-SB pellet (202.01% ± 8.16) seemed to have higher cell proliferation properties than HAp-WC pellet (145.7% ± 5.11) and HAp-CM pellet (71.53% ± 3.61) due to its higher aspect ratio, and hence higher surface area for the cells to adhere. In a detailed study, it is observed that both techniques had their advantages, and there were no significant disadvantages observed.
Topics: Humans; Durapatite; Schiff Bases; Biocompatible Materials; Bone and Bones; Chemical Precipitation
PubMed: 37907060
DOI: 10.1016/j.jmbbm.2023.106200 -
Life (Basel, Switzerland) Aug 2023is a flagellated unicellular protozoan that colonizes the small intestine, causing the diarrheal disease called giardiasis. The production of extracellular vesicles...
is a flagellated unicellular protozoan that colonizes the small intestine, causing the diarrheal disease called giardiasis. The production of extracellular vesicles (EVs) by and the role of these EVs in the parasite's interaction with the host have been described. According to biogenesis, EVs are grouped mainly into large (microvesicles-derived from the plasma membrane) and small (exosomes-derived from multivesicular bodies). Populations of EVs are heterogeneous, and improved methods to separate and study them are needed to understand their roles in cell physiology and pathologies. This work aimed to enrich the large extracellular vesicles (LEVs) of in order to better understand the roles of these vesicles in the interaction of the parasite with the host. To achieve the enrichment of the LEVs, we have modified our previously described method and compared it by protein dosage and using Nano tracking analysis. vesiculation was induced by incubation in a TYI-S-33 medium without serum, to which 1 mM of CaCl was added at 37 °C for 1 h. Then, the supernatant was centrifuged at 15,000× for 1 h (15 K 1 h pellet), 15,000× for 4 h (15 K 4 h pellet) and 100,000× for 1.5 h (100 K 1h30 pellet). The pellet (containing EVs) was resuspended in 1× PBS and stored at 4 °C for later analysis. The EVs were quantified based on their protein concentrations using the Pierce BCA assay, and by nanoparticle tracking analysis (NTA), which reports the concentration and size distribution of the particles. The NTA showed that direct ultracentrifugation at 100,000× for 1.5 h and centrifugation at 15,000× for 4 h concentrated more EVs compared to centrifugation at 15,000× for 1 h. Additionally, it revealed that centrifugation at 15,000× 4 h was able to concentrate at the same particle concentration levels as a direct ultracentrifugation at 100,000× for 1.5 h. As for the enrichment of LEVs, the NTA has shown a higher concentration of LEVs in direct ultracentrifugation at 100,000× for 1.5 h, and in centrifugation at 15,000× for 4 h, compared to centrifugation at 15,000× for 1 h. Our results have shown that the most used method at 15,000× for 1 h is not enough to obtain a representative population of large EVs, and we suggest that LEVs released by can be better enriched by direct ultracentrifugation at 100,000× for 1.5 h, or by centrifugation at 15,000× for 4 h.
PubMed: 37763203
DOI: 10.3390/life13091799