In recent years, the coamorphous drug delivery system has been established as a promising formulation approach for delivering poorly water-soluble drugs. The coamorphous solid is a single-phase system containing an active pharmaceutical ingredient (API) and other low molecular weight molecules that might be pharmacologically relevant APIs or excipients. These formulations exhibit considerable advantages over neat crystalline or amorphous material, including improved physical stability, dissolution profiles, and potentially enhanced therapeutic efficacy. This review provides a comprehensive overview of coamorphous drug delivery systems from the perspectives of preparation, physicochemical characteristics, physical stability, in vitro and in vivo performance. Furthermore, the challenges and strategies in developing robust coamorphous drug products of high quality and performance are briefly discussed.
Pulmonary arterial hypertension (PAH), a rare condition and a hyperproliferative vascular disorder, is characterized by vascular remodeling of the intrapulmonary arterial wall, resulting in elevated pulmonary vascular resistance, right ventricular hypertrophy, and eventually right heart failure and death. Although animal models can reproduce the chief feature of the disease, i.e., elevated pulmonary arterial pressure, they do not accurately portray the biology of human PAH. Further, the FDA Modernization Act 2021 encourages using alternatives to animal models such as organ chip models in non-clinical studies because the latter models are not only humane but also expected to expedite drug development and discovery. As such, we recently established the feasibility of designing, developing, and deploying a PAH-on-a-chip for studying PAH pathophysiology and screening for anti-PAH drugs in our laboratory. This PAH-chip model mimics five layers of the pulmonary artery and allows the growing of adult PAH cells in separate channels, facilitating cell–ell and cell–matrix interactions. Importantly, the device can reconstruct the major clinical features of PAH, including arterial muscularization and plexiform lesions. Here, we described a step-by-step detailed method of PAH-chip design and fabrication and cell seeding on the device so that any biologist can prepare the device and study PAH pathophysiology in a laboratory setting. Our protocol is different from other published methods of PDMS-based chips in terms of application of the device, which is PAH-on-a-chip, and the depth of the details. We envision that this method of chip fabrication can also be used to study other pulmonary vascular disorders.
We present a robust, low-cost fabrication method for implementation in multilayer soft photolithography to create a PDMS microfluidic chip with features possessing multiple height levels. This fabrication method requires neither a cleanroom facility nor an expensive UV exposure machine. The central part of the method stays on the alignment of numerous PDMS slabs on a wafer-scale instead of applying an alignment for a photomask positioned right above a prior exposure layer using a sophisticated mask aligner. We used a manual XYZR stage attached to a vacuum tweezer to manipulate the top PDMS slab. The bottom PDMS slab sat on a rotational stage to conveniently align with the top part. The movement of the two slabs was observed by a monocular scope with a coaxial light source. As an illustration of the potential of this system for fast and low-cost multilayer microfluidic device production, we demonstrate the microfabrication of a 3D microfluidic chaotic mixer. A discussion on another alternative method for the fabrication of multiple height levels is also presented, namely the micromilling approach.
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