Expectedly, the tablets compressed at the highest pressure exhibited a much lower porosity than those compacted at the lowest pressure levels. Porosity is notably influenced by the rate at which the turret rotates. The variability of process parameters resulted in tablet batches demonstrating an average porosity that fell within the range of 55% and 265%. Within each batch, a spectrum of porosity values exists, with their standard deviation falling between 11% and 19%. The objective of performing destructive measurements of disintegration time was to create a predictive model that correlates tablet porosity with disintegration time. While testing suggested a reasonable model, small systematic errors could potentially affect disintegration time measurements. Ambient storage for nine months influenced tablet properties, as evidenced by the findings of terahertz measurements.
Chronic inflammatory bowel diseases (IBD) find an important therapeutic agent in the form of the monoclonal antibody, infliximab. treatment medical The macromolecular structure of the substance presents a significant obstacle to oral delivery, thus restricting administration to parenteral routes. An alternative approach to infliximab treatment involves administering it rectally, localizing its effects at the disease site, reducing its systemic exposure through the digestive tract, and enhancing its bioavailability and effectiveness. The creation of flexible-dosage drug products using digital models is facilitated by the advanced technology of 3D printing. The current study scrutinized the practicality of incorporating semi-solid extrusion 3D printing into the production of infliximab-containing suppositories for local inflammatory bowel disease therapy. Different printing inks, consisting of Gelucire (48/16 or 44/14) combined with coconut oil, and/or purified water, were subject to an investigation. The infliximab solution, following its reconstitution in water, was found to be directly incorporated into the Gelucire 48/16 printing ink matrix, and the extrusion process yielded well-defined suppositories. Due to the importance of water content and temperature in preserving infliximab's potency, the impact of changing the printing ink and parameter settings on infliximab's efficacy was examined through quantification of its binding capability (the amount that actively binds to its antigen). Although drug loading assays indicated the integrity of infliximab post-printing, the presence of water alone diminished binding capacity to only 65%. Despite prior assumptions, the mixture's binding capacity of infliximab improves by a substantial 85% when oil is introduced. These promising results indicate that 3D printing has the capability to be utilized as a novel platform for creating dosage forms containing biopharmaceuticals, offering a remedy to the patient compliance challenges observed with injectables and satisfying their unmet therapeutic needs.
For rheumatoid arthritis (RA), a powerful therapeutic intervention is the selective suppression of tumor necrosis factor (TNF) signaling, focusing on the TNF receptor 1 (TNFR1). For rheumatoid arthritis therapy, novel composite nucleic acid nanodrugs were meticulously crafted to simultaneously curb TNF binding and TNFR1 multimerization, thereby reinforcing the inhibition of TNF-TNFR1 signaling. To achieve this goal, a novel peptide, Pep4-19, which inhibits TNFR1 clustering, was isolated from TNFR1. Employing a DNA tetrahedron (TD), the resulting peptide and the TNF-binding inhibiting DNA aptamer Apt2-55 were integrally or separately anchored, leading to nanodrugs with different spatial distributions of Apt2-55 and Pep4-19, labeled TD-3A-3P and TD-3(A-P). Our research indicated that Pep4-19 augmented the survival rate of inflammatory L929 cells. The compounds TD-3A-3P and TD-3(A-P) exhibited a shared effect of inhibiting caspase 3, reducing cell apoptosis, and preventing FLS-RA migration. TD-3A-3P exhibited a greater range of motion and better anti-inflammatory responses for Apt2-55 and Pep4-19 than TD-3(A-P). In addition, TD-3A-3P substantially reduced symptoms in mice exhibiting collagen-induced arthritis (CIA), and its anti-rheumatic effectiveness following intravenous injection was equivalent to delivery through transdermal microneedles. Polyhydroxybutyrate biopolymer Regarding RA treatment, the study's effective strategy is demonstrated by targeting TNFR1 in dual fashion, while also revealing microneedles as a promising avenue for administering drugs.
Personalized medicine benefits from pharmaceutical 3D printing (3DP), a burgeoning technology that facilitates the creation of highly adaptable dosage forms. Over the past two years, national medicine regulatory bodies have engaged in consultations with external stakeholders to modify regulatory frameworks, thereby incorporating point-of-care manufacturing practices. Decentralized manufacturing (DM) entails pharmaceutical companies preparing feedstock intermediates (pharma-inks), then delivering them to DM sites for the production of the final medicinal compound. The feasibility of this model is examined in this study, encompassing considerations for both its production and quality assurance. A manufacturing partner created efavirenz-infused granulates (0-35% weight/weight) and sent them to a 3DP facility located in a different country. Printlets (3D-printed tablets), with a mass range from 266 to 371 milligrams, were later created using direct powder extrusion (DPE) 3DP. Following the in vitro drug release test, all printlets exhibited more than an 80% drug load release within 60 minutes. A process analytical technology (PAT), incorporating an in-line near-infrared spectroscopy system, was instrumental in determining the drug concentration within the printlets. Using partial least squares regression, calibration models were created, revealing excellent linearity (R² = 0.9833) and accuracy (RMSE = 10662). For the first time, this investigation details the use of an inline near-infrared system for real-time analysis of printlets generated from pharma-inks produced by a pharmaceutical company. This work, through its demonstration of the proposed distribution model's feasibility, creates a springboard for the investigation of additional PAT tools pertinent to quality control in 3DP point-of-care manufacturing.
An essential oil-based microemulsion (ME) formulation and optimization of the anti-acne drug tazarotene (TZR) utilizing either jasmine oil (Jas) or jojoba oil (Joj) was the focus of this study. To generate TZR-MEs, two experimental designs (Simplex Lattice Design) were implemented, and the resulting formulations were characterized for droplet size, polydispersity index, and viscosity. Subsequent in vitro, ex vivo, and in vivo studies were conducted on the selected formulations. Trametinib ic50 TZR-selected MEs demonstrated spherical particle morphology, appropriate droplet size, homogeneous dispersion, and satisfactory viscosity. The Jas-selected ME displayed a markedly higher accumulation of TZR throughout all skin layers compared to the Joj ME, according to the ex vivo skin deposition study. Lastly, regarding antimicrobial activity, TZR proved ineffective against P. acnes; however, its activity was dramatically enhanced when incorporated into the chosen microbial extracts. Our in vivo investigation into P. acnes-infected mouse ears demonstrated that our chosen Jas and Joj MEs achieved significantly higher ear thickness reductions, reaching 671% and 474%, respectively, compared to the 4% reduction observed with the existing market product. Ultimately, the study concluded that essential oil-based microemulsions, particularly those with jasmin, demonstrate promise as a carrier for topical treatment of acne vulgaris with TZR.
Employing physical interconnection for permeation, this study aimed to develop the Diamod as a dynamic gastrointestinal transfer model. A study of the intraluminal dilution of a cyclodextrin-based itraconazole solution and the adverse food effect on indinavir sulfate was integral to validating the Diamod, with clinical data revealing that solubility, precipitation, and permeation processes were strongly correlated with systemic exposure. The Diamod's simulation precisely mirrored the effect of water consumption on how a Sporanox solution behaved within the gastrointestinal tract. Water absorption resulted in a considerable decrease in duodenal itraconazole levels, contrasting with the observed levels without water intake. Although duodenal behavior differed, the quantity of permeated itraconazole remained unaffected by water consumption, as seen in live animal studies. Furthermore, the Diamod faithfully reproduced the detrimental effect of food on indinavir sulfate. Studies contrasting fasted and fed states highlighted a detrimental food effect, attributable to escalated stomach acidity, indinavir's entrapment within colloidal aggregates, and a delayed gastric emptying rate under conditions of food ingestion. The Diamod model, therefore, effectively facilitates in vitro mechanistic investigations concerning drug performance in the gastrointestinal system.
Active pharmaceutical ingredients (APIs) with poor water solubility benefit from amorphous solid dispersion (ASD) formulations, leading to consistent improvements in dissolution and solubility. Formulating a stable material that resists undesirable transformations like crystallization and amorphous phase separation during storage is crucial, as is ensuring optimal dissolution properties for the formulation, including sustained high supersaturation over an extended period. Both are essential aspects of successful formulation development. This study evaluated the capability of ternary ASD formulations (comprising one API and two polymers), using hydroxypropyl cellulose in combination with either poly(vinylpyrrolidone-co-vinyl acetate) (PVP VA64) or hydroxypropyl cellulose acetate succinate, to maintain the amorphous state of fenofibrate and simvastatin and improve their dissolution rates throughout storage. Thermodynamic predictions using the PC-SAFT model for each polymeric combination identified the optimal polymer ratio, the maximum, thermodynamically stable API load, and the degree of miscibility between the two polymers.