Application of 3D printing technology for the development of dose adjustable geriatric and pediatric formulation of celecoxib.

Developing safe and effective formulations for the geriatric and pediatric population is a challenging task due to issues of swallowability and palatability. The lack of standardized procedures for pediatric formulations further complicates the process. Manipulating adult formulations for children can lead to suboptimal efficacy and safety concerns. To overcome these challenges, minitablets or spinklets are preferred for the geriatric and pediatric population due to their smaller size and flexible dose adjustment. The aim of this study is the development of a 3D printed spinklets formulation of celecoxib, a nonsteroidal anti-inflammatory drug, using hot melt extrusion to address the limitations of traditional manufacturing methods. Three different formulations of celecoxib were prepared using Poly-2-ethyl-tetra-oxazoline (Aquazol) with and without surfactant. Subsequently, the mechanical properties and solubility of the drug-loaded filaments were evaluated. Solid state characterization confirmed the drug conversion into an amorphous form during the extrusion process, Computer-aided design software facilitate sprinklets design for fused deposition modeling and scanning electron microscopy assess the surface morphology. Sophorolipids plasticize better than TPGS, resulting in lowering processing temperatures during melt extrusion. In vitro drug release showed successful enhancements in the dissolution of oral medications for pediatric patients, considering their distinctive physiological characteristics. Overall, this study demonstrates the successful development of PEtOx-based 3D printed celecoxib sprinklets by coupling hot-melt extrusion and 3D printing technology. Future exploration holds the potential to revolutionize pharmaceutical production and advance personalized medication formulations.

Recent advancement in targeted therapy and role of emerging technologies to treat cancer.

Cancer is a complex disease that causes abnormal cell growth and spread. DNA mutations, chemical or environmental exposure, viral infections, chronic inflammation, hormone abnormalities, etc., are underlying factors that can cause cancer. Drug resistance and toxicity complicate cancer treatment. Additionally, the variability of cancer makes it difficult to establish universal treatment guidelines. Next-generation sequencing has made genetic testing inexpensive. This uncovers genetic mutations that can be treated with specialty drugs. AI (artificial intelligence), machine learning, biopsy, next-generation sequencing, and digital pathology provide personalized cancer treatment. This allows for patient-specific biological targets and cancer treatment. Monoclonal antibodies, CAR-T, and cancer vaccines are promising cancer treatments. Recent trial data incorporating these therapies have shown superiority in clinical outcomes and drug tolerability over conventional chemotherapies. Combinations of these therapies with new technology can change cancer treatment and help many. This review discusses the development and challenges of targeted therapies like monoclonal antibodies (mAbs), bispecific antibodies (BsAbs), bispecific T cell engagers (BiTEs), dual variable domain (DVD) antibodies, CAR-T therapy, cancer vaccines, oncolytic viruses, lipid nanoparticle-based mRNA cancer vaccines, and their clinical outcomes in various cancers. We will also study how artificial intelligence and machine learning help find new cancer treatment targets.

Formulation strategies for the development of high drug-loaded amorphous solid dispersions.

Amorphous solid dispersions (ASD) have gained tremendous attention over the past two decades as one of the most promising techniques for enhancing the solubility of poorly water-soluble drugs. However, low drug loading is one of the major challenges of ASD technology that limits its commercialization to only a few drug candidates. Increasing the drug loading increases the risk of recrystallization during storage (solid state) and/or during dissolution (solution state). Various formulation and process-related strategies have been explored that open the possibility of formulating high drug-loaded ASDs without the risk of recrystallization. Here, we review various formulation approaches, such as the use of surfactants, mesoporous silicas, polymer combinations, in situ thermal crosslinking, structural modification of polymeric carriers, and surface nanocoating using minerals. We also discuss the mechanisms by which these approaches inhibit solid state and/or solution state recrystallization.

Ibrutinib amorphous solid dispersions with enhanced dissolution at colonic pH for the localized treatment of colorectal cancer.

Colorectal cancer (CRC) is the second most leading cause of cancer-related deaths worldwide. Ibrutinib (IBR), the first in class bruton tyrosine kinase (BTK) inhibitor has promising anticancer activity. In this study, we aimed to develop a hot melt extrusion based amorphous solid dispersions (ASD) of IBR with enhanced dissolution at colonic pH and assess the anticancer activity against colon cancer cell lines. Since colonic pH is higher in CRC patients compared to healthy individuals, Eudragit® FS100 was used as pH dependent polymeric matrix for colon enabled release of IBR. Poloxamer 407, TPGS and poly(2-ethyl-2-oxazoline) were screened as plasticizer and solubilizer to improve the processability and solubility. Solid state characterization and filament appearance confirmed that IBR was molecularly dispersed within FS100 + TPGS matrix. In-vitro drug release of ASD showed > 96% drug release within 6 h at colonic pH with no precipitation for 12 h. Contrary, crystalline IBR showed negligible release. ASD with TPGS showed significantly higher anticancer activity in 2D and multicellular 3D spheroids of colon carcinoma cell lines (HT-29 and HT-116). The outcomes of this research suggested that ASD with a pH dependent polymer is a promising strategy to improve solubility and an effective approach in colorectal cancer targeting.