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The introduction of three-dimensional (3D) printing in the pharmaceutical field has made great strides towards innovations in the way drugs are designed and manufactured. In this ...study, digital light processing (DLP) technique was used to fabricate oral dosage forms of different shapes with zolpidem tartrate (ZT), incorporated within its therapeutic range. Formulation factors, such as poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) 400 (PEG 400) ratio, as well as water content, were varied in combination with the surface area/volume (SA/V) ratio to achieve immediate drug release. Hypromellose (HPMC) was used as a stabilizing agent of photoreactive suspensions in an attempt to prevent drug sedimentation and subsequent variations in drug content uniformity. Oral dosage forms with doses in the range from 0.15 mg to 6.37 mg, showing very rapid and rapid drug dissolution, were successfully fabricated, confirming the potential of this technique in drug manufacturing with the ability to provide flexible dose adjustments and desirable release profiles by varying formulation factors and geometry of 3D models. DSC (differential scanning calorimetry), XRPD (X-ray powder diffraction) and scanning electron microscopy (SEM) showed that ZT remained in a crystalline form within printed dosage forms and no interactions were found between ZT and polymers.
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Laser sintering, known as powder bed fusion–laser beam (PBF-LB), offers promising potential for the fabrication of patient-specific drugs. The aim of this study was to provide an ...insight into the PBF-LB process with regard to the process parameters, in particular the laser hatching distance, and its influence on the properties of zolpidem tartrate (ZT) tablets. PHARMACOAT® 603 was used as the polymer, while Candurin® Gold Sheen and AEROSIL® 200 were added to facilitate 3D printing. The particle size distribution of the powder blend showed that the layer height should be set to 100 µm, while the laser hatching distance was varied in five different steps (50, 100, 150, 200 and 250 µm), keeping the temperature and laser scanning speed constant. Increasing the laser hatching distance and decreasing the laser energy input led to a decrease in the colour intensity, mass, density and hardness of the ZT tablets, while the disintegration and dissolution rate were faster due to the more fragile bonds between the particles. The laser hatching distance also influenced the ZT dosage, indicating the importance of this process parameter in the production of presonalized drugs. The absence of drug-polymer interactions and the amorphization of the ZT were confirmed.
Abstract
C
10
H
9
BrN
2
, orthorhombic,
P
2
1
2
1
2
1
(no. 19),
a
= 5.9070(3) Å,
b
= 9.2731(7) Å,
c
= 17.5641(14) Å,
V
= 962.09(12) Å
3
,
Z
= 4,
R
gt
(
F
) = 0.0504,
wR
ref
(
F
2
) = 0.0947, ...T = 293(2) K.
Abstract
C
4
H
2
N
3
BrO
4
·H
2
O, monoclinic,
P
2
1
/
c
(no. 14),
a
= 7.177(2) Å,
b
= 10.999(3) Å,
c
= 10.414(3) Å,
β
=
100.145
(
11
)
∘
$100.145{(11)}^{\circ }$
,
V
= 809.3(4) Å
3
,
Z
= 4,
R
...g
t
${R}_{\mathrm{g}\mathrm{t}}$
(
F
) = 0.0379,
w
R
r
e
f
$w{R}_{\mathrm{r}\mathrm{e}\mathrm{f}}$
(
F
2
) = 0.0714, T = 200 K
Cardiac resynchronization therapy (CRT) has recently emerged as an effective treatment for patients with moderate to severe systolic heart failure and ventricular dyssynchrony. The purpose of the ...present study was to determine whether improvements in left ventricular (LV) size and function were associated with CRT.
Doppler echocardiograms were obtained at baseline and at 3 and 6 months after therapy in 323 patients enrolled in the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial. Of these, 172 patients were randomized to CRT on and 151 patients to CRT off. Measurements were made of LV end-diastolic and end-systolic volumes, ejection fraction, LV mass, severity of mitral regurgitation (MR), peak transmitral velocities during early (E-wave) and late (A-wave) diastolic filling, and the myocardial performance index. At 6 months, CRT was associated with reduced end-diastolic and end-systolic volumes (both P<0.001), reduced LV mass (P<0.01), increased ejection fraction (P<0.001), reduced MR (P<0.001), and improved myocardial performance index (P<0.001) compared with control. beta-Blocker treatment status did not influence the effect of CRT. Improvements with CRT were greater in patients with a nonischemic versus ischemic cause of heart failure.
CRT in patients with moderate-to-severe heart failure who were treated with optimal medical therapy is associated with reverse LV remodeling, improved systolic and diastolic function, and decreased MR. LV remodeling likely contributes to the symptomatic benefits of CRT and may herald improved longer-term survival.
Previous studies have suggested that cardiac resynchronization achieved through atrial-synchronized biventricular pacing produces clinical benefits in patients with heart failure who have an ...intraventricular conduction delay. We conducted a double-blind trial to evaluate this therapeutic approach.
Four hundred fifty-three patients with moderate-to-severe symptoms of heart failure associated with an ejection fraction of 35 percent or less and a QRS interval of 130 msec or more were randomly assigned to a cardiac-resynchronization group (228 patients) or to a control group (225 patients) for six months, while conventional therapy for heart failure was maintained. The primary end points were the New York Heart Association functional class, quality of life, and the distance walked in six minutes.
As compared with the control group, patients assigned to cardiac resynchronization experienced an improvement in the distance walked in six minutes (+39 vs. +10 m, P=0.005), functional class (P<0.001), quality of life (-18.0 vs. -9.0 points, P= 0.001), time on the treadmill during exercise testing (+81 vs. +19 sec, P=0.001), and ejection fraction (+4.6 percent vs. -0.2 percent, P<0.001). In addition, fewer patients in the group assigned to cardiac resynchronization than control patients required hospitalization (8 percent vs. 15 percent) or intravenous medications (7 percent vs. 15 percent) for the treatment of heart failure (P<0.05 for both comparisons). Implantation of the device was unsuccessful in 8 percent of patients and was complicated by refractory hypotension, bradycardia, or asystole in four patients (two of whom died) and by perforation of the coronary sinus requiring pericardiocentesis in two others.
Cardiac resynchronization results in significant clinical improvement in patients who have moderate-to-severe heart failure and an intraventricular conduction delay.
Interatrial block (IAB) is an electrocardiographic pattern describing the conduction delay between the right and left atria. IAB is classified into 3 degrees of block that correspond to decreasing ...conduction in the region of Bachmann's bundle. Although initially considered benign in nature, specific subsets of IAB have been associated with atrial arrhythmias, elevated thromboembolic stroke risk, cognitive impairment, and mortality. As the pathophysiologic relationships between IAB and stroke are reinforced, investigation has now turned to the potential benefit of early detection, atrial imaging, cardiovascular risk factor modification, antiarrhythmic pharmacotherapy, and stroke prevention with oral anticoagulation. This review provides a contemporary overview of the epidemiology, pathophysiology, diagnosis, and management of IAB, with a focus on future directions.
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