Role of multi-detector computed tomography in congenital heart diseases

Background: The study aimed to assess sensitivity, specificity and accuracy of CT scan in diagnosing various cardiovascular anomalies in patients with complex congenital heart disease; to obtain additional information in pre-operative patients, inconclusive on echocardiography; and to compare results of multi-detector computed tomography (MDCT) with cardiac catheter angiography (CCA) in accurately delineating the cardiovascular morphological features and to determine if MDCT can replace diagnostic CCA in evaluation of complex CHD.Methods: In this prospective, comparative, single-centre study, a total 50 patients were included in the study aged between 6 days to 17 years. All patients were referred by pediatric cardiologists between August, 2014 and November, 2016. All patients had undergone initial echocardiography and final diagnosis was confirmed by comparing MDCT data with CCA.Results: Total of 177 cardiovascular anomalies are found in our study of 50 patients out of these 3 cases of VSD and one case of ASD was missed on CT angiography and its overall accuracy as compared to catheter angiography was found to be 97.1% Its accuracy in evaluation of TOF, DORV, TAPVC, TA TGA, COA, right sided aortic arch, MAPVC, persistent SVC, PDA, PS, vascular sling and coronary cameral fistula was 100%.Conclusions: The MDCT is found comparable to CCA in the diagnosis of extra cardiac vascular anomalies but the overall sensitivity in the diagnosis of intra-cardiac anomalies is little lower. It can be used as a substitute to CCA in complex CHD and is very helpful tool in preoperative planning and postoperative follow-up

Co-processing pharmaceutical ingredients to engineer novel multifunctional excipients

The simplicity and cost-effectiveness of direct compression makes it a preferred method of commercial tablet manufacturing. Excipients play a central role in determining the success of direct compression. Currently available directly compressible excipients are typically effective at relatively high proportion of >50% (w/w). For high-dose APIs, incorporation of such high excipient load is inappropriate, as this may necessitate the formation of large tablets, which may be difficult to ingest. Thus, high-dose APIs (especially for poorly flowable and difficult to compact) are often considered unsuitable for tablet manufacturing by direct compression. In interactive mixtures, small guest particles (typically <10 µm) adhere to larger host particles. We hypothesized that small binder particles could express a binder action as well as a flow additive action, if they could form a suitable interactive mixture with large APIs. However, many such small particles are highly cohesive, which limits their de-agglomeration, dispersion and consequently the ability to form a homogeneous interactive mixture. Thus, the aim of this thesis was to understand the impact of the cohesion of small binder particles on their interactive mixing behaviour and consequently extension of their potential excipient performance i.e., binder and flow additive actions. A model pharmaceutical binder, polyvinylpyrrolidone (PVP) was co-sprayed with L-leucine to engineer small low-cohesion binder particles. In these composite particles, L-leucine enriched at the surfaces and manipulated the surface physico-chemical properties (such as morphology, surface energy and its crystalline character), which allowed control over cohesion. Low cohesion small binder particles de-agglomerated efficiently and formed a more homogeneous interactive mixture with paracetamol (active pharmaceutical ingredient, API) compared with high cohesion binder particles. The homogeneous interactive mixing allowed small binder particles to express enhanced binder and flow additive actions. The flow additive action improved while inherent binder activity reduced with reducing cohesion. This decline in binder activity was attributed to the reduction in the compactability (or bonding ability) of binder particles. However, manipulation of mechanical properties (increasing plastic deformability) allowed improvement of the binder activity of such low cohesion binder particles. High performance excipients are necessary to facilitate direct compression of high-dose APIs. Our study showed that binder and flow additive action are mutually exclusive excipient properties and the knowledge of interactive mixing allowed creation of composite excipients with elements of both flow additive and binder action. Manipulation of the surface physico-chemical and mechanical properties via smart particle engineering enabled small binder particles to express an optimum flow additive and binder performances. Thus, this knowledge could enable rational engineering and development of high-performance direct compression excipients, which would enable direct compression of poorly compactable and poorly flowable high-dose APIs.

Improved Physical Stability and Aerosolization of Inhalable Amorphous Ciprofloxacin Powder Formulations by Incorporating Synergistic Colistin

This study aimed to develop dry powder inhaler (DPI) combination formulations of ciprofloxacin and colistin for use in respiratory infections. Effects of colistin on physical stability and aerosolization of spray-dried ciprofloxacin were examined. The combination DPI formulations were produced by co-spray drying colistin and ciprofloxacin in mass ratios of 1:1, 1:3, and 1:9. Colistin and ciprofloxacin were also co-sprayed with l-leucine in the mass ratio of 1:1:1. The physical and aerosolization stability of the selected co-sprayed formulations stored at 20, 55, and 75% relative humidity (RH) were examined. Formulation characterizations were carried out using powder X-ray diffraction (PXRD) for crystallinity, scanning electron microscopy for morphology and particle size distribution, and dynamic vapor sorption for moisture sorption. Particle surface analysis was performed using X-ray photoelectron spectroscopy, energy dispersive X-ray spectrometry, and nano-time-of-flight secondary ion mass spectrometry. Potential intermolecular interactions were studied using Fourier-transform infrared spectroscopy (FTIR). Aerosol performance was evaluated using a multistage liquid impinger with a RS01 monodose inhaler device. PXRD diffractograms showed that the co-spray-dried colistin–ciprofloxacin formulation in the mass ratio (1:1) was amorphous at 55% RH for up to 60 days; whereas the co-spray-dried colistin–ciprofloxacin (1:3) and colistin–ciprofloxacin (1:9) crystallized after storage for 3 days at 55% RH. However, the extent of crystallization for the combination formulations was less as compared to the spray-dried ciprofloxacin alone formulation. Surface morphology of the co-spray-dried formulations at different concentrations did not change even after storage at 55% RH for 60 days, unlike the spray-dried ciprofloxacin alone powder which became rougher after 3 days of storage at 55% RH. Surface analysis data indicated surface enrichment of colistin in the co-spray-dried formulations. Increasing colistin concentration on the composite particles surfaces improved aerosol performance of ciprofloxacin. FTIR data demonstrated intermolecular interactions between colistin and ciprofloxacin, thereby delaying and/or preventing crystallization of ciprofloxacin when co-spray-dried. Co-spray drying ciprofloxacin with colistin in the mass ratio (1:1) completely prevented crystallization of ciprofloxacin at 55% RH for up to 60 days. However, the colistin–ciprofloxacin formulation (1:1) began to fuse when stored at 75% RH due to moisture absorption resulting in a compromised aerosol performance. In contrast, the colistin–ciprofloxacin–leucine (1:1:1) formulation demonstrated no particle fusion, enabling a stable aerosol performance at 75% RH for 7 days. This study demonstrated that incorporation of colistin in the spray-dried formulations can improve physical stability and aerosolization of amorphous ciprofloxacin at 55% RH. At 75% RH, further addition of l-leucine in the formulation prevented particle fusion and deterioration in aerosol performance, attributed to the enrichment of nonhygroscopic l-leucine on the particle surface