scholarly journals Development of a 3D-Printed Dosing Platform to Aid in Zolpidem Withdrawal Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1684
Author(s):  
Silke Henry ◽  
Lien De Vadder ◽  
Milan Decorte ◽  
Susanna Francia ◽  
Magali Van Steenkiste ◽  
...  
Keyword(s):  
Surface Defects ◽  
Benzodiazepine Receptor ◽  
Immediate Release ◽  
Processing Temperature ◽  
First Report ◽  
Photolytic Degradation ◽  
Withdrawal Therapy ◽  
3D Printed ◽  
Flexible Dosing

The long-term use of benzodiazepine receptor agonists (BZRAs) is associated with multiple side effects, such as increased sedation, hangover or an elevated risk of dependency and abuse. Unfortunately, the long-term use of BZRAs is reaching worrying intake rates, and therefore, the need for action is high. It was demonstrated already that the overall willingness of patients for deprescription increased when a slow dose reduction scheme with the possibility for dose increase, if needed, is employed. The current study aims to develop a flexible dosing platform of zolpidem hemitartrate (ZHT) to facilitate such withdrawal therapy. As this is the first report on the extrusion and 3D printing of ZHT, its thermal behaviour and sensitivity towards photolytic degradation was characterised. It was shown that ZHT possesses multiple polymorphs and was especially prone to oxidative photolysis. Next, a variety of immediate release polymers (Eudragit EPO, Kollidon VA64, Kollidon 12PF and Soluplus) were blended and extruded with Polyox WSR N10 to investigate their feedability and printability by mechanical and rheological analysis. The addition of PEO was shown to enable printing of these brittle pharmaceutical polymers, although the processing temperature was deemed critical to avoid surface defects on the resulting filaments. An EPO(70)PEO(30) system was selected based on its suitable mechanical properties and low hygroscopicity favoring ZHT stability. The matrix was blended with 1% or 10% API. The effect of certain printing parameters (caplet size, nozzle diameter, % overlap) on dissolution behaviour and caplet weight/dimensions/quality was assessed. A flexible dosing platform capable of delivering <1 mg and up to 10 mg of ZHT was created. Either caplet modification (incorporation of channels) or disintegrant addition (Primojel, Explotab, Ac-Di-Sol, Primellose and Polyplasdone-XL) failed to achieve an immediate release profile. This study provides the first report of a 3D-printed flexible dosing platform containing ZHT to aid in withdrawal therapy.

scholarly journals A millifluidic chip for cultivation of fish embryos and toxicity testing fabricated by 3D printing technology

RSC Advances ◽  
2021 ◽  
Vol 11 (33) ◽  
pp. 20507-20518
Author(s):  
Petr Panuška ◽  
Zuzana Nejedlá ◽  
Jiří Smejkal ◽  
Petr Aubrecht ◽  
Michaela Liegertová ◽  
...  
Keyword(s):  
3D Printing ◽  
Toxicity Testing ◽  
Toxicity Screening ◽  
Printing Technology ◽  
3D Printing Technology ◽  
Fish Embryos ◽  
3D Printed ◽  
Novel Design

A novel design of 3D printed zebrafish millifluidic system for embryonic long-term cultivation and toxicity screening has been developed. The chip unit provides 24 cultivation chambers and a selective individual embryo removal functionality.

scholarly journals Recurrent contracted sockets treated with personalized, three-dimensionally printed conformers and buccal grafts

2021 ◽  
pp. 112067212110000
Author(s):  
Annabel LW Groot ◽  
Jelmer S Remmers ◽  
Roel JHM Kloos ◽  
Peerooz Saeed ◽  
Dyonne T Hartong
Keyword(s):  
Three Dimensional ◽  
Case Series ◽  
Secondary Outcome ◽  
Retrospective Case ◽  
Upper Eyelid ◽  
Ocular Prosthesis ◽  
Buccal Mucosal Graft ◽  
Custom Made ◽  
3D Printed

Purpose: Recurrent contracted sockets are complex situations where previous surgeries have failed, disabling the wear of an ocular prosthesis. A combined method of surgery and long-term fixation using custom-made, three-dimensional (3D) printed conformers is evaluated. Methods: Retrospective case series of nine patients with recurrent excessive socket contraction and inability to wear a prosthesis, caused by chemical burns ( n = 3), fireworks ( n = 3), trauma ( n = 2) and enucleation and radiotherapy at childhood due to optic nerve glioma ( n = 1) with three average previous socket surgeries (range 2–6). Treatment consisted of a buccal mucosal graft and personalized 3D-printed conformer designed to be fixated to the periosteum and tarsal plates for minimal 2 months. Primary outcome was the retention of an ocular prosthesis. Secondary outcome was the need for additional surgeries. Results: Outcomes were measured at final follow-up between 7 and 36 months postoperatively (mean 20 months). Eight cases were able to wear an ocular prosthesis after 2 months. Three cases initially treated for only the upper or only the lower fornix needed subsequent surgery for the opposite fornix for functional reasons. Two cases had later surgery for cosmetic improvement of upper eyelid position. Despite pre-existing lid abnormalities (scar, entropion, lash deficiency), cosmetic outcome was judged highly acceptable in six cases because of symmetric contour and volume, and reasonably acceptable in the remaining two. Conclusions: Buccal mucosal transplant fixated with a personalized 3D-designed conformer enables retention of a well-fitted ocular prosthesis in previously failed socket surgeries. Initial treatment of both upper and lower fornices is recommended to avoid subsequent surgeries for functional reasons.

Enlargement of cerebrospinal fluid spaces in long-term benzodiazepine abusers

1987 ◽  
Vol 17 (4) ◽  
pp. 869-873 ◽  
Author(s):  
C. Schmauss ◽  
J.-C. Krieg
Keyword(s):  
Low Dose ◽  
Matched Control ◽  
Control Group ◽  
High Dose ◽  
Withdrawal Therapy ◽  
The Mean ◽  
Dose Dependent ◽  
Dose Dependent Effect ◽  
Age And Sex

SynopsisIn 17 benzodiazepine (BDZ) dependent in-patients a CT scan was performed before initiation of withdrawal therapy. The evaluation of the ventricular to brain ratio (VBR) by standardized and computerized measurements revealed significantly higher mean VBRs for both high-and low-dose BDZ-dependent patients compared to the mean VBR of an age- and sex-matched control group. In addition, the mean VBR of high-dose BDZ-dependent patients (N = 8) was significantly higher than the mean VBR of low-dose BDZ-dependent patients (N = 9). This difference could not be accounted for by the age of the patients or duration of BDZ-dependency and, therefore, suggests a dose-dependent effect of BDZs on the enlargement of internal CSF-spaces. On the other hand, higher values for the width of external CSF-spaces were found to be related to increasing age of the patients and duration of BDZ-dependency.

Dissolution Characteristics and Morphology of Large-sized Scorodite Particles Synthesized from Fe(II) and As(V) in Aqueous Solution

2012 ◽  
Vol 31 (4-5) ◽  
pp. 451-458 ◽  
Author(s):  
S. Fujieda ◽  
K. Shinoda ◽  
T. Inanaga ◽  
M. Abumiya ◽  
S. Suzuki
Keyword(s):  
Electron Microscopy ◽  
Aqueous Solution ◽  
Surface Defects ◽  
Atmospheric Temperature ◽  
Orthorhombic Structure ◽  
X Ray ◽  
Long Term Storage ◽  
Transmission Electron ◽  
Term Storage

AbstractA novel process for preparing scorodite particles with a diameter of approximately 20 µm from Fe(II) and As(V) in aqueous solution has been developed by DOWA Metals and Mining. In the present study, the dissolution characteristics of iron and arsenic from the scorodite particles synthesized by this process have been investigated under different conditions. The results show that the concentration of arsenic dissolved from the particles in aqueous solution is very low, but it has a complicated dependence on the temperature and pH of the solution. Transmission electron microscopy (TEM) with an energy dispersive X-ray spectrometer (EDS) was used to analyze the morphology, structure, and composition of the scorodite particles. The results indicate that the scorodite particles exhibit a nearly octahedral shape with planes composed of almost (111) planes in the orthorhombic structure. The concentration of iron at the surface of the particles is higher than that of iron inside of the particles. This characteristic morphology, along with the minimal surface defects of the scorodite particles, is considered to be responsible for the low dissolution of arsenic from the particles in aqueous solution. Atmospheric temperature and solution conditions were also found to be important for the safe, long-term storage of arsenic using scorodite particles.

Pituitary and gonadal responses to the long-term pulsatile administration of gonadotrophin-releasing hormone in fetal fetal sheep

1997 ◽  
Vol 153 (3) ◽  
pp. 385-391 ◽  
Author(s):  
G B Thomas ◽  
A N Brooks
Keyword(s):  
Plasma Concentrations ◽  
Reproductive Function ◽  
Inverse Correlation ◽  
Experimental Period ◽  
Immediate Release ◽  
Late Gestation ◽  
Plasma Testosterone ◽  
Fetal Sheep ◽  
Pulsatile Administration

Abstract The fetal hypothalamo–pituitary–gonadal axis reaches a peak in activity at mid-gestation and this is followed by a period of suppression which persists until the onset of puberty. The decline in gonadotrophic activity during late gestation is thought to reflect the maturation of central and peripheral feedback signals. In order to establish if sustained pituitary responsiveness is rate limiting to the reinstatement of reproductive function, we have examined the endocrine consequences of repeated pulsatile GnRH administration to male and fetal sheep during late gestation. Beginning on day 121 of gestation (term=145 days) chronically catheterized fetal sheep were given i.v. pulses of either 500 ng GnRH or saline every 2 h for 14 days. Pituitary and gonadal responses were assessed by measuring changes in plasma concentrations of LH, FSH, inhibin and testosterone (in male fetuses) in response to the first pulse of GnRH on day 1 and to the corresponding pulse on days 4, 7, 10 and 14. In response to the first pulse of GnRH there was an immediate release of LH, with the peak response being significantly (P<0·01) greater than on subsequent days. In male fetuses each pulse of LH was followed by a rise in plasma testosterone concentrations within 40–60 min. The amplitude of these testosterone responses increased significantly (P<0·01) after 9 days of treatment despite a decline in the plasma LH response. Basal FSH concentrations increased progressively (P<0·05) during pituitary stimulation with GnRH in both male and female fetuses. Immunoreactive inhibin concentrations were significantly (P<0·05) higher in males than in females, and there was a gradual increase throughout the experimental period irrespective of treatment. We observed no inverse correlation between inhibin and FSH concentrations. These data show that pulsatile administration of GnRH to fetal sheep during late gestation results in sustained re-activation of pituitary–gonadal function. The decline in fetal gonadotrophins, which is a characteristic feature of late gestation, is therefore likely to result from inadequate GnRH secretion from the fetal hypothalamus rather than an inhibition of pituitary function by peripheral feedback signals. Journal of Endocrinology (1997) 153, 385–391

scholarly journals Long-lasting impact of starvation experience on fly activity and place preference

2020 ◽  
Author(s):  
Deepthi Mahishi ◽  
Tilman Triphan ◽  
Ricarda Hesse ◽  
Wolf Huetteroth
Keyword(s):  
Activity Patterns ◽  
Petri Dish ◽  
Sensory Stimulation ◽  
Place Preference ◽  
Substrate Layer ◽  
Hunger Motivation ◽  
Internal States ◽  
3D Printed ◽  
Integration Strategies

AbstractAnimal behaviours are demonstrably governed by sensory stimulation, previous experience and internal states like hunger. With increasing hunger, priorities shift towards foraging and feeding. During foraging, flies are known to employ efficient path integration strategies. However, general long-term activity patterns for both hungry and satiated flies in conditions of foraging remain to be better understood. Similarly, little is known about how chronic contact chemosensory stimulation affects locomotion. To address these questions, we have developed a novel, simplistic fly activity tracking setup – the Panopticon. Using a 3D-printed Petri dish inset, our assay allows recording of walking behaviour, of several flies in parallel, with all arena surfaces covered by a uniform substrate layer. We tested two constellations of providing food: i) in single patches, and ii) omnipresent within the substrate layer. Fly tracking is done with FIJI, further assessment, analysis and presentation is done with a custom-built MATLAB analysis framework. We find that starvation history leads to a long-lasting reduction in locomotion, as well as a delayed place preference for food patches not driven by immediate hunger motivation.

First report on the efficacy of l-alanine-based in situ-forming implants for the long-term parenteral delivery of drugs

2005 ◽  
Vol 108 (2-3) ◽  
pp. 433-441 ◽  
Author(s):  
François Plourde ◽  
Aude Motulsky ◽  
Anne-Claude Couffin-Hoarau ◽  
Didier Hoarau ◽  
Huy Ong ◽  
...  
Keyword(s):  
First Report ◽  
Parenteral Delivery ◽  
In Situ Forming ◽  
In Situ Forming Implants

On effect of chemical-assisted mechanical blending of barium titanate and graphene in PVDF for 3D printing applications

2020 ◽  
pp. 089270572094537
Author(s):  
Ravinder Sharma ◽  
Rupinder Singh ◽  
Ajay Batish
Keyword(s):  
Mechanical Properties ◽  
Barium Titanate ◽  
3D Printing ◽  
Comparative Study ◽  
Process Parameters ◽  
Processing Temperature ◽  
Melt Mixing ◽  
Twin Screw ◽  
3D Printed ◽  
The Comparative Study

The polyvinylidene difluoride + barium titanate (BaTiO3) +graphene composite (PBGC) is one of the widely explored thermoplastic matrix due to its 4D capabilities. The number of studies has been reported on the process parameters of twin-screw extruder (TSE) setup (as mechanical blending technique) for the development of PBGC in 3D printing applications. But, hitherto, little has been reported on chemical-assisted mechanical blending (CAMB) as solution mixing and melt mixing technique combination for preparation of PBGC. In this work, for preparation of PBGC feedstock filaments, CAMB has been used. Also, the effect of process parameters of TSE on the mechanical, dimensional, morphological, and thermal properties of prepared filament of PBGC have been explored followed by 3D printing. Further, a comparative study has been reported for the properties of prepared filaments with mechanically blended composites. Similarly, the mechanical properties of 3D printed parts of chemically and mechanically blended composites have been compared. The results of tensile testing for CAMB of PBGC show that the filament prepared with 15% BaTiO3 is having maximum peak strength 43.00 MPa and break strength 38.73 MPa. The optical microphotographs of the extruded filaments revealed that the samples prepared at 180°C extruder temperature and 60 r/min screw speed have minimum porosity, as compared to filaments prepared at high extruder temperature. Further, the results of the comparative study revealed that the filaments of CAMB composites show better mechanical properties as compared to the filaments of mechanically mixed composites. However, the dimensional properties were almost similar in both cases. It was also found that the CAMB composites have better properties at low processing temperature, whereas mechanically blended composites show better results at a higher temperature. While comparing 3D printed parts, tensile strength of specimens fabricated from CAMB was more than the mechanically blended PBGC.

Upregulation of the GABAA/benzodiazepine receptor during anoxia in the freshwater turtle brain

1995 ◽  
Vol 268 (5) ◽  
pp. R1332-R1335 ◽  
Author(s):  
P. L. Lutz ◽  
S. L. Leone-Kabler
Keyword(s):  
Gabaa Receptors ◽  
Benzodiazepine Receptor ◽  
Freshwater Turtle ◽  
Gamma Aminobutyric Acid ◽  
Binding Assays ◽  
Binding Properties ◽  
Inhibitory Neurotransmitter ◽  
N2 Atmosphere ◽  
Dissociation Constant Kd

The freshwater turtle brain survives anoxia by decreasing its energy expenditure. During this anoxic period there is a sustained release of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). This study investigated whether there was a corresponding change in the binding properties of the GABAA/benzodiazepine (GABA/BDZ) receptor. Turtles (Trachemys scripta) were subjected to a 100% N2 atmosphere for up to 24 h. After exposure, the cerebral cortex was dissected out, and saturation binding assays for GABA/BDZ receptors were performed using the radioligand [3H]flunitrazepam. Control turtles had a dissociation constant (Kd) of 1.97 +/- 0.54 nM and a receptor density (Bmax) of 2,404 +/- 221 fmol/mg protein. The Kd showed no significant change over 24 h of anoxia. However, significant increases were seen in Bmax after 12 h (21%, P < 0.05) and 24 h (29%, P < 0.01) of anoxia. We suggest that a long-term upregulation of GABAA receptors occurs in the anoxic turtle brain that acts to increase the inhibitory effectiveness of the released GABA and thereby contributes to anoxia survival of the turtle.

Change in Surface Morphology by Addition of Impurity Elements in 4H-SiC Solution Growth with Si Solvent

2015 ◽  
Vol 821-823 ◽  
pp. 14-17 ◽  
Author(s):  
Naoyoshi Komatsu ◽  
Takeshi Mitani ◽  
Tetsuo Takahashi ◽  
Tomohisa Kato ◽  
Kazuhisa Kurashige ◽  
...  
Keyword(s):  
Surface Defects ◽  
Group Iv ◽  
Solution Growth ◽  
High Quality ◽  
Group V ◽  
Bulk Crystal Growth ◽  
Group Iii ◽  
Growth From Solution ◽  
Impurity Elements

In solution growth of 4H-SiC, we have investigated changes in macrostep height with addition of the Group III (B, Al, Ga), Group IV (Ge, Sn), Group V (N) elements, and transition metals (Ti, V, Cr, Ni) to Si solvents, in order to find additives improving severe step bunching which often occurs during growth. The addition of Al, B, Sn, N, and V decreased the average macrostep height compared with the crystal grown with Si solvents. The addition of Al, B, Sn, N, and V suppressed the generation of trench-shaped surface defects in long-term growth of 10 hours. This result demonstrated that the addition of Al, B, Sn, N, and V has an advantage to achieve high quality bulk crystal growth from solution.

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