Background Intestinal GC-C/cGMP pathway may be involved in visceral hypersensitivity and fluid secretion in irritable bowel syndrome (IBS). The guanylcyclase C agonist linaclotide, approved for IBS- constipation, is contraindicated in children as it may cause severe diarrhea. In contrast, drugs increasing cGMP by inhibiting phosphodiesterase 5 (PDE-5) are well tolerated in children with pulmonary hypertension. Accordingly, we investigated whether beneficial effects of linaclotide in IBS might be shared by PDE-5inhibitor tadalafil without the severe diarrhea reported for linaclotide. Since depression is commonly comorbid with IBS and is implicated in its pathophysiology; and since tadalafil is absorbed systemically and crosses blood brain barrier, whereas linaclotide does not, impact of both drugs on behavioral changes in IBS was also investigated. Methods 72 rats were divided into 6groups (control naive, control tadalafil, control linaclotide, untreated IBS, IBS tadalafil, and IBS linaclotide-treated). IBS was induced by 0 to 4 °C intragastric saline for 14 days. find protocol Results Both drugs reduced visceral hypersensitivity and colonic C fos. Tadalafil, and to a greater extent, linaclotide increased colonic cGMP, fecal pellets (8.66 ± 4.6 (IBS),versus14.8 ± 3.3(tadalafil), 20 ± 1.2(linaclotide), fecal water content (29.8 ± 5.5 (IBS), versus 47.83 ± 12.6 (tadalafil), 63.58 ± 11.6 (linaclotide) and reduced intestinal transit time (% distance travelled 29 ± 6.1(IBS), versus 40.58 + 7.5(tadalafil), 51.83 ± 8.3(linaclotide). Tadalafil, but not linaclotide, increased hippocampal cGMP, and improved behavioral tests scores compared to linaclotide (immobility time 97.3 ± 12.5 s (IBS) versus 68 ± 12.8(tadalafil), 80 ± 17.06 (linaclotide). Conclusion Systemic PDE-5 inhibitors might be alternatives to locally acting guanyl cyclase agonists in IBS, inducing less severe diarrhea and more beneficial effects on the associated behavioral changes.Intravitreal (IVT) injection is currently the state of the art for drug delivery to the back of the eye. Drug Products (DP) intended for IVT injections usually pose challenges such as a very low injection volume (e.g. 50 μL) and high injection forces. DPs in vials are typically transferred and injected using disposable polymer syringes, which can feature a silicone oil (SO) coating. In our syringe in-use study, we compared dead volume, total SO content and SO layer distributions of three IVT transfer injection syringes. We assessed multiple potential impact factors such as protein concentration, needle gauge, injection speed, surfactant type and the impact of the in-use hold time on sub-visible particle (SvP) formation and injection forces. Pronounced differences were observed between the syringes regarding SvP generation. Siliconized syringes showed higher SvP counts as compared to non-siliconized syringes. In some cases injection forces exceeded 20 N, which caused needles to burst off during injection. The syringes also showed relevant differences in total SO content and dead volume. In conclusion, specific consideration in the selection of an adequate transfer injection syringe are required. This includes extensive testing and characterization under intended and potential in-use conditions and the development of in-use handling procedures.Lyophilized protein formulations containing highly concentrated proteins often have long reconstitution times. The goal was to understand the role of formulation in mediating the reconstitution time. Formulation variables such as % total solids, protein concentration, protein-to-sugar ratio, different proteins and inclusion of a crystallizable excipient were investigated for their effect on cake properties influencing reconstitution namely, cake wettability, penetration of reconstitution fluid into the cake, cake disintegration and cake porous structure. Additionally, several measures of viscosity were also evaluated for their effect on reconstitution time. Reconstitution time was primarily influenced by the “concentrated formulation viscosity” with negligible contributions from % total solids and protein concentration. “Concentrated formulation viscosity” was sensitive to both protein-to-sugar ratio and the protein itself. Partial crystallinity in the final cake also expedited reconstitution. Wettability, liquid penetration into the cake, cake disintegration tendency and cake porous structure were found to be invariant for amorphous cakes and did not correlate with reconstitution time. However, these properties were sensitive to the presence of crystallinity and resulted in faster reconstitution at least of the partially crystalline cakes. “Concentrated formulation viscosity” strongly correlated with reconstitution times of amorphous cakes, providing insights on the steps involved in the reconstitution of amorphous formulations.In pharmaceutical development alternative drug delivery modalities are being increasingly employed. One example is an implant, which achieves gradual drug release in patients over a period of many months or years. Due to the complexity of these long-acting formulations, advanced physical characterization methods are desirable as screening tools during protracted formulation development. Imaging methods are of particular interest due to their ability to interrogate the structure and composition of implants spatially across multiple length scales (macro, micro, nano). In this work, spatiochemical imaging is shown to interrogate many crucial drug product attributes of solid implants overall implant structure, drug distribution, micro-domain size and orientation, agglomeration, porosity and defects, drug/excipient interface, dissolution process, and release mechanism. Imaging methods facilitate a detailed understanding of the process/structure correlation to inform on formulation selection, process parameter optimization, and batch consistency. Numerous case studies of implant applications with imaging are discussed. Methods utilized are X-ray computed tomography (XRCT), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS) imaging, and Raman microscopy. The imaging data is complemented with solid-state nuclear magnetic resonance (ssNMR). Altogether, these examples demonstrate that complementary imaging methods are highly effective for analyzing complex and novel pharmaceutical modalities such as solid implants.