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The success and cost regarding belimumab and voclosporin pertaining to lupus nephritis.
SLNs encapsulated with siRNA can also be successfully transformed into aerosolizable dry powder by TFFD, and subjecting the siRNA-encapsulated SLNs to TFFD did not negatively affect the function of the siRNA. It is concluded that TFFD represents a promising method to prepare aerosolizable dry powder of lipid nanoparticles.Minimizing variability in the feeding process is important for continuous manufacturing since materials are fed individually and can impact the final product. This study demonstrates the importance of measuring powder properties and highlights the need to characterize the feeding performance both offline with multiple refills and in the intended configuration for the continuous manufacturing equipment. The standard grade hydroxypropyl methylcellulose (HPMC) had material buildup on the loss-in-weight feeder barrel from triboelectric charging and resulted in more mass flow excursions and failed refills which were not observed with the direct compression grades. The location of the electrostatic buildup changed when the feeder was connected to a hopper instead of feeding offline into a collection bucket. Overall, the direct compression HPMC exhibited better flow which resulted in more accurate loss-in-weight feeding with less excursions from the target mass flow and all refills were completed in the first attempt. The improvements with the direct compression HPMC would be beneficial when running any continuous process (wet granulation, roller compaction, or direct compression) or other processes where loss-in-weight feeding is utilized, such as melt extrusion or twin screw granulation.Localized delivery to oral mucositis ulcerations requires specialized dosage forms, (e.g. selleck compound in situ forming gels) delivered to the site in relatively low volumes. However, this is challenging for drugs with low solubility such as Bupivacaine γ-Linoleate (Bup-γL). The objective of this study is to develop an in situ forming gel with enhanced loading of Bup-γL for oral mucositis pain control. Two co-solvents (PEG400 and ethanol) and eight solubilizers (Tween 80, sodium lauryl sulfate, Cremophor® RH40, Cremophor® EL, Kolliphor® HS 15, Soluplus®, PEG 3350 and PEG8000) were screened for their capability to solubilize Bup-γL. Among all tested solubilizers, sodium lauryl sulfate (SLS) showed the highest solubilizing capacity (8.83 ± 0.94 mg/mL). This was considered to be a consequence of the similarity between the structure of SLS and Bup-γL. On the addition of SLS to the in situ forming gels, the drug loading was enhanced from ~6.5 to ~10.5 mg/ml. The formulations were characterized for their gelation temperature, rheological properties, in vitro drug release and short-term storage stability. The gelation temperatures of the in situ forming gel formulations were significantly reduced with enhanced drug loading. The in vitro drug release profiles showed good fit to both the first order and the Higuchi models. Formulations with SLS demonstrated sustained drug release (time to plateau ~7 h) compared with formulations without SLS (time to plateau ~3.5 h). This study offers an effective strategy to enhance drug loading of in situ forming gels. The enhanced drug loading will reduce the dosing volume and as such is expected to reduce any unwanted numbing of the healthy mucosa.The aim of this study was to better understand the underlying drug release mechanisms in poly(lactic-co-glycolic acid) (PLGA) microparticles in which the drug is dispersed in the form of tiny particles ("monolithic dispersions"). Differently sized diprophylline-loaded microparticles were prepared using a solid-in-oil-in-water solvent extraction/evaporation technique. The microparticles were characterized before and after exposure to phosphate buffer pH 7.4 at 4, 20 and 37 °C. In vitro drug release was measured from ensembles and single microparticles. GPC, DSC, SEM, gravimetric analysis, drug solubility measurements and optical microscopy were used to elucidate the importance of polymer swelling & degradation, drug dissolution and diffusion. The diprophylline was initially homogeneously distributed throughout the microparticles in the form of tiny crystals. The burst release (1st phase) was strongly temperature-dependent and likely attributable to the dissolution of drug crystals with direct surface access (potentially via tiny pores). The about constant release rate during the 2nd phase also strongly depended on the temperature. It can probably be explained by the dissolution of drug crystals in surface near regions undergoing local swelling. During the observation period, the 3rd (again rapid) drug release phase was only observed at 37 °C, and seems to be caused by substantial PLGA swelling throughout the entire microparticles. This phase starts as soon as a critical polymer molecular weight of about 25 kDa is reached Significant amounts of water penetrate into the systems, dissolving the remaining diprophylline crystals and substantially increasing the mobility of the dissolved drug molecules. Thus, this study provides additional experimental evidence (obtained at lower temperatures) confirming the hypothesized root causes for drug release from PLGA microparticles containing dispersed drug particles.Partitioning tests in water are early-stage standard experiments during the development of pharmaceutical formulations, e.g. of lipid-based drug delivery system (LBDDS). The partitioning behavior of the active pharmaceutical ingredient (API) between the fatty phase and the aqueous phase is a key property, which is supposed to be determined by those tests. In this work, we investigated the API partitioning between LBDDS and water by in-silico predictions applying the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) and validated these predictions experimentally. The API partitioning was investigated for LBDDS comprising up to four components (cinnarizine or ibuprofen with tricaprylin, caprylic acid, and ethanol). The influence of LBDDS/water mixing ratios from 1/1 up to 1/200 (w/w) as well as the influence of excipients on the API partitioning was studied. Moreover, possible API crystallization upon mixing the LBDDS with water was predicted. This work showed that PC-SAFT is a strong tool for predicting the API partitioning behavior during in-vitro tests.
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