Current Issue : October - December Volume : 2020 Issue Number : 4 Articles : 5 Articles
Maintaining chemical and physical stability of the product during freeze-drying is\nimportant but challenging. In addition, freeze-drying is typically associated with long process\ntimes. Therefore, mechanistic models have been developed to maximize drying efficiency without\naltering the chemical or physical stability of the product. Dried product mass transfer resistance (Rp)\nis a critical input for these mechanistic models. Currently available techniques to determine Rp only\nprovide an estimation of the mean Rp and do not allow measuring and determining essential local (i.e.,\nintra-vial) Rp differences. In this study, we present an analytical method, based on four-dimensional\nmicro-computed tomography (4D-microCT), which enables the possibility to determine intra-vial Rp\ndifferences. Subsequently, these obtained Rp values are used in a mechanistic model to predict the\ndrying time distribution of a spin-frozen vial. Finally, this predicted primary drying time distribution\nis experimentally verified via thermal imaging during drying. It was further found during this\nstudy that 4DmicroCT uniquely allows measuring and determining other essential freeze-drying process\nparameters such as the moving direction(s) of the sublimation front and frozen product layer thickness,\nwhich allows gaining accurate process knowledge. To conclude, the study reveals that the variation\nin the end of primary drying time of a single vial could be predicted accurately using 4D-microCT as\nsimilar results were found during the verification using thermal imaging....
The use of amorphous drug delivery systems is an attractive approach to improve the\nbioavailability of low molecular weight drug candidates that suffer from poor aqueous solubility.\nHowever, the pharmaceutical performance of many neat amorphous drugs is compromised by their\ntendency for recrystallization during storage and lumping upon dissolution, which may be improved\nby the application of coatings on amorphous surfaces. In this study, hot melt coating (HMC) as a\nsolvent-free coating method was utilized to coat amorphous carvedilol (CRV) particles with tripalmitin\ncontaining 10% (w/w) and 20% (w/w) of polysorbate 65 (PS65) in a fluid bed coater. Lipid coated\namorphous particles were assessed in terms of their physical stability during storage and their drug\nrelease during dynamic in vitro lipolysis. The release of CRV during in vitro lipolysis was shown to\nbe mainly dependent on the PS65 concentration in the coating layer, with a PS65 concentration of 20%\n(w/w) resulting in an immediate release profile. The physical stability of the amorphous CRV core,\nhowever, was negatively affected by the lipid coating, resulting in the recrystallization of CRV at the\ninterface between the crystalline lipid layer and the amorphous drug core. Our study demonstrated\nthe feasibility of lipid spray coating of amorphous CRV as a strategy to modify the drug release from\namorphous systems but at the same time highlights the importance of surface-mediated processes for\nthe physical stability of the amorphous form....
Fused deposition modeling (FDMTM) is a 3D-printing technology of rising interest for the\nmanufacturing of customizable solid dosage forms. The coupling of hot-melt extrusion with FDMTM\nis favored to allow the production of pharma-grade filaments for the printing of medicines. Filament\ndiameter consistency is a quality of great importance to ensure printability and content uniformity of\n3D-printed drug delivery systems. A systematical process analysis referring to filament diameter\nvariations has not been described in the literature. The presented study aimed at a process setup\noptimization and rational process analysis for filament fabrication related to influencing parameters\non diameter inhomogeneity. In addition, the impact of diameter variation on the critical quality\nattributes of filaments (mechanical properties) and uniformity of mass of printed drug-free dosage\nforms was investigated. Process optimization by implementing a winder with a special haul-off unit\nwas necessary to obtain reliable filament diameters. Subsequently, the optimized setup was used for\nconduction of rational extrusion analysis. The results revealed that an increased screw speed led to\ndiameter fluctuations with a decisive influence on the mechanical resilience of filaments and mass\nuniformity of printed dosage forms. The specific feed load was identified as a key parameter for\nfilament diameter consistency....
Dissolution and disintegration of solid dosage forms such as multiple-layer tablet with\ndifferent active ingredients depend on formulation and properties used in the formulations, and it\nmay sometimes result in counterintuitive release kinetics. In this manuscript, we investigate the\nbehavior of combined acetylsalicylic acid and mefenamic acid bi- and triple-layer formulations.\nWe show that the simulation model with a cellular automata predicted the impact of the inert layer\nbetween the different active ingredients on each drug release and provide a good agreement with the\nexperimental results. Also, it is shown that the analysis based on the Noyesâ??Whitney equation in\ncombination with a cellular automata-supported dissolution and disintegration numerical solutions\nexplain the nature of the unexpected effects. We conclude that the proposed simulation approach\nis valuable to predict the influence of material attributes and process parameters on drug release\nfrom multicomponent and multiple-layer pharmaceutical tablets and to help us develop the drug\nproduct formulation....
Fenofibrate-loaded electrospun microfibrous sheets were prepared in an attempt to enhance\nthe dissolution of the poorly soluble antihyperlipidemic agent and to improve its bioavailability.\nPhysicochemical changes that appeared during the electrospinning process were monitored using\na wide array of solid-state characterization techniques, including attenuated total reflectance\nFourier-transformed infrared spectroscopy and positron annihilation lifetime spectroscopy, while fiber\nmorphology was monitored via scanning electron microscopy. Dissolution studies carried out both\nin 0.025 M sodium dodecyl sulfate and in water revealed an immediate release of the active agent,\nwith an approximately 40-fold release rate enhancement in water when compared to the micronized\nactive agent. The dramatic increase in dissolution was attributed partially to the amorphous form of\nthe originally crystalline active agent and the rapid disintegration of the electrospun microfibrous\nsheet due to its high surface area and porosity. The obtained results could pave the way for a\nformulation of the frequently used antihyperlipidemic agent with increased bioavailability....
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