Introduction: Currently, hot melt extrusion (HME) is a promising technology in the pharmaceutical industry, as evidenced by its application to manufacture various FDA-approved commercial products in the market. HME is extensively researched for enhancing the solubility and bioavailability of poor water-soluble drugs, taste masking, and modifying release in drug delivery systems. Additionally, its other novel opportunities or pharmaceutical applications, and capability for continuous manufacturing are being investigated. This efficient, industrially scalable, solvent-free, continuous process can be easily automated and coupled with other novel platforms for continuous manufacturing of pharmaceutical products.
Areas covered: This review focuses on updates on solubility enhancement of poorly water-soluble drugs and process analytical tools such as UV/visible spectrophotometry; near-infrared spectroscopy; Raman spectroscopy; and rheometry for continuous manufacturing, with a special emphasis on fused deposition modeling 3D printing.
Expert opinion: The strengths, weakness, opportunities, threats (SWOT) and availability of commercial products confirmed wide HME applicability in pharmaceutical research. Increased interest in continuous manufacturing processes makes HME a promising strategy for this application. However, there is a need for extensive research using process analytical tools to establish HME as a dependable continuous manufacturing process. 相似文献
Product temperature (Tb) and drying time constitute critical material attributes and process parameters in the lyophilization process and especially during the primary drying stage. In the study, we performed a temperature measurement by the sublimation rate (TMbySR) to monitor the Tb value and determine the end point of primary drying. First, the water vapor transfer resistance coefficient through the main pipe from the chamber to the condenser (Cr) was estimated via the water sublimation test. The use of Cr value made it possible to obtain the time course of Tb from the measurement of pressure at the drying chamber and at the condenser. Second, a Flomoxef sodium bulk solution was lyophilized by using the TMbySR system. The outcome was satisfactory when compared with that obtained via conventional sensors. The same was applicable for the determination of the end point of primary drying. A laboratory-scale application of the TMbySR system was evidenced via the experiment using 220-, 440-, and 660-vial scales of lyophilization. The outcome was not dependent on the loading amount. Thus, the results confirmed that the TMbySR system is a promising tool in laboratory scale. 相似文献
This paper addresses the relevance of automated content testing for the rapid automated process development (RAPD). Our previous work demonstrated that RAPD allowed a fast and efficient development of a continuous capsule-filling process. Target was the mean weight and the relative standard deviation of the weight. Likewise important are the content and the content uniformity. However, an implementation demands a certain level of automation. In general, technology is available that can detect active pharmaceutical ingredient (API) inside the capsules but the final application is linked to additional development and investment in machinery. To eliminate doubts regarding the benefits of an automated content check within the RAPD we present an application example. First, an X-ray system was used to detect barium sulfate accurately inside capsules. Second, a process was developed where barium sulfate was filled. The concentration of excipients was modified in the experiments, as well as the setting of the process parameter. The obtained model provided an explicit understanding of the process. Subsequently, the content uniformity model was compared to a model of the capsule weight relative standard deviation, confirming the benefits of an automated content check in the RAPD. Moreover, we presented another example illustrating the advantages of a connected continuous filling process, which permits evaluation of all process steps and their interactions (i.e. evaluation of the entire process). 相似文献
Age estimation of cadavers from post-mortem “chest plate” using conventional radiography, which involves radiographic assessment of ossification around the sternum and rib ends, has been evaluated without fruitful results. This study examined the value of images of the chest plate obtained by three-dimensional post-mortem CT for estimation of age at time of death in a Japanese population. Five chest plate ossification scores were evaluated in 320 subjects, including ossification of the first costal cartilage (OF), ossification of the second to seventh costal cartilages at the rib (OR) and sternal (OS) ends, fusion of the manubriosternal joint (FM), and fusion of the xiphisternal joint (FX). OS was found to have the highest correlation with age while FM had no significant correlation. The best composite score for age estimation was the summative score for both sides of the OS and the right side of the OF and FX, for which the coefficient of determination (R2) and the standard error of estimation (SEE) were 0.608 and 12.44 years, respectively, for men and 0.590 and 14.65 years for women. The accuracy of the model was tested in a further 26 male and 24 female subjects, and the accuracy rate within the first SEE was 57.69% and 70.83%, respectively. This rapid and non-invasive method of age estimation in the chest plate area is superior to conventional methods and could be useful for estimation of age at time of death in the Japanese population. 相似文献
Mortality remains high for patients on the waiting list for organ transplantation. A marked imbalance between the number of available organs and recipients that need to be transplanted persists. Organs from deceased donors are often declined due to perceived and actual suboptimal quality. Adequate donor management offers an opportunity to reduce organ injury and maximise the number of organs than can be offered in order to respect the donor's altruistic gift. The cornerstones of management include: correction of hypovolaemia; maintenance of organ perfusion; prompt treatment of diabetes insipidus; corticosteroid therapy; and lung protective ventilation. The interventions used to deliver these goals are largely based on pathophysiological rationale or extrapolations from general critical care patients. There is currently insufficient high-quality evidence that has assessed whether any interventions in the donor after brain death may actually improve immediate post-transplant function and long-term graft survival or recipient survival after transplantation. Improvements in our understanding of the underlying mechanisms following brain death, in particular the role of immunological and metabolic changes in donors, offer promising future therapeutic opportunities to increase organ utilisation. Establishing a UK donor management research programme involves consideration of ethical, logistical and legal issues that will benefit transplanted patients while respecting the wishes of donors and their families. 相似文献
BackgroundHippocampal oscillations play a critical role in the ontogeny of allocentric memory in rodents. During the critical period for memory development, hippocampal theta is the driving force behind the temporal coordination of neuronal ensembles underpinning spatial memory. While known that hippocampal oscillations are necessary for normal spatial cognition, whether disrupted hippocampal oscillatory activity during the critical period impairs long-term spatial memory is unknown. Here we investigated whether disruption of normal hippocampal rhythms during the critical period have enduring effects on allocentric memory in rodents.Objective/hypothesisWe hypothesized that disruption of hippocampal oscillations via artificial regulation of the medial septum during the critical period for memory development results in long-standing deficits in spatial cognition.MethodsAfter demonstrating that pan-neuronal medial septum (MS) optogenetic stimulation (465 nm activated) regulated hippocampal oscillations in weanling rats we used a random pattern of stimulation frequencies to disrupt hippocampal theta rhythms for either 1Hr or 5hr a day between postnatal (P) days 21–25. Non-stimulated and yellow light-stimulated (590 nm) rats served as controls. At P50-60 all rats were tested for spatial cognition in the active avoidance task. Rats were then sacrificed, and the MS and hippocampus assessed for cell loss. Power spectrum density of the MS and hippocampus, coherences and voltage correlations between MS and hippocampus were evaluated at baseline for a range of stimulation frequencies from 0.5 to 110 Hz and during disruptive hippocampal stimulation. Unpaired t-tests and ANOVA were used to compare oscillatory parameters, behavior and cell density in all animals.ResultsNon-selective optogenetic stimulation of the MS in P21 rats resulted in precise regulation of hippocampal oscillations with 1:1 entrainment between stimulation frequency (0.5–110 Hz) and hippocampal local field potentials. Across bandwidths MS stimulation increased power, coherence and voltage correlation at all frequencies whereas the disruptive stimulation increased power and reduced coherence and voltage correlations with most statistical measures highly significant (p < 0.001, following correction for false detection). Rats receiving disruptive hippocampal stimulation during the critical period for memory development for either 1Hr or 5hr had marked impairment in spatial learning as measured in active avoidance test compared to non-stimulated or yellow light-control rats (p < 0.001). No cell loss was measured between the blue-stimulated and non-stimulated or yellow light-stimulated controls in either the MS or hippocampus.ConclusionThe results demonstrated that robust regulation of hippocampal oscillations can be achieved with non-selective optogenetic stimulation of the MS in rat pups. A disruptive hippocampal stimulation protocol, which markedly increases power and reduces coherence and voltage correlations between the MS and hippocampus during the critical period of memory development, results in long-standing spatial cognitive deficits. This spatial cognitive impairment is not a result of optogenetic stimulation-induced cell loss. 相似文献