Drugs crystals
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Advances in Drug Crystallization and Delivery Systems
Liquid Crystal Emulsions in Drug Delivery
Liquid crystals (LCs) have emerged as a promising medium for drug delivery due to their ability to provide controlled and sustained release of drugs. A novel system involving drug crystallization encapsulated within liquid crystal emulsions has been developed, utilizing lamellar liquid crystals formed by hydrogenated lecithin. This structure mimics the lipid structure of the skin's stratum corneum, making it an effective carrier for non-steroidal anti-inflammatory drugs (NSAIDs) like ketoprofen. The drug exists as a crystal within the hydrophobic core of the emulsion, which enhances its thermal stability and biocompatibility, and provides sustained release properties, making it suitable for topical applications1.
Crystal Structures of Pharmaceuticals
The physical arrangement of molecules within a crystal significantly influences the properties of pharmaceutical solids, including their dissolution rate and stability. Understanding these relationships is crucial for selecting the most appropriate form of an active pharmaceutical ingredient (API) for drug development. Advances in crystal structure determination and computational prediction have enhanced our ability to engineer crystals with desired properties, thereby improving the processing, formulation, and efficacy of solid pharmaceuticals2.
Drug-Induced Crystal Nephropathy
Certain medications that are insoluble in human urine can precipitate within the renal tubules, leading to crystal nephropathy. This condition can cause both acute and chronic kidney injury. Drugs such as sulfadiazine, acyclovir, indinavir, triamterene, and methotrexate are known to cause this condition. Recent studies have also identified other medications, including orlistat and ciprofloxacin, as potential causes. Factors such as intravascular volume depletion, underlying kidney disease, and metabolic disturbances that alter urinary pH can increase the risk of crystal nephropathy3.
Pharmaceutical Cocrystals for Improved Drug Properties
Pharmaceutical cocrystals, formed by combining an API with a pharmaceutically acceptable coformer, can systematically enhance the physicochemical properties of a drug without altering its molecular structure. This approach can improve solubility, permeability, bioavailability, and other critical properties. The development of cocrystals has led to the creation of drugs with better efficacy and stability, and continuous manufacturing technologies have facilitated their large-scale production4 6.
Liquid Crystal Nanoparticles in Drug Delivery
Liquid crystal nanoparticles, particularly lyotropic liquid crystals (LLCs) like cubosomes and hexosomes, have shown great potential in drug delivery applications. These nanoparticles offer efficient, controlled, and targeted drug release. The unique microstructures and physicochemical properties of LLCs make them suitable for solubilizing various bioactive molecules and protecting them from degradation. However, further research is needed to develop reliable large-scale production methods for these nanoparticles5 10.
Profiling Drug Crystallization in the Skin
Drug crystallization in the skin can affect the delivery of transdermal and topical formulations. Advanced techniques such as synchrotron SAXS/WAXS analysis and confocal Raman spectroscopy (CRS) have been employed to monitor drug crystallization in situ, particularly in the deeper layers of the skin. These methods allow for the detection of drug crystals without damaging the skin samples, providing valuable insights into the distribution and crystallization behavior of drugs within the skin7.
Conclusion
The field of drug crystallization and delivery systems is rapidly evolving, with significant advancements in the use of liquid crystals, pharmaceutical cocrystals, and nanoparticles. These innovations offer promising solutions for improving drug stability, bioavailability, and targeted delivery, ultimately enhancing therapeutic outcomes. Continued research and development in this area are essential for overcoming existing challenges and realizing the full potential of these advanced drug delivery systems.
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Most relevant research papers on this topic
A novel drug delivery system -- drug crystallization encapsulated liquid crystal emulsion.
The novel drug delivery system, drug crystallization encapsulated liquid crystal emulsion, improves thermal stability, biocompatibility, and sustained release properties for topical cosmeceuticals.
Crystal structures of drugs: advances in determination, prediction and engineering
Advances in crystal structure determination and computational approaches can help design novel pharmaceutical compounds with desired physical and mechanical properties.
Highly CitedDrug-induced crystal nephropathy: an update
Crystal nephropathy is caused by several medications, including sulfadiazine, acylcovir, indinavir, triamterene, and MTX, and can be exacerbated by underlying kidney disease and metabolic disturbances.
Systematic ReviewHighly CitedCrystal Engineering of Pharmaceutical Cocrystals in the Discovery and Development of Improved Drugs.
Pharmaceutical cocrystals, designed using supramolecular synthons, enable improved drug efficacy and bioavailability without changing the drug's molecular structure.
Highly CitedLiquid crystal nanoparticles for commercial drug delivery
Liquid crystal nanoparticles show potential for efficient, controlled, and target-selective drug delivery, but a reliable method for large-scale production is needed for widespread usage.
Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates.
Crystal engineering can improve the bioavailability of poorly soluble drugs by altering crystallisation processes and molecular properties, potentially enhancing oral absorption and safety.
Highly CitedProfiling of drug crystallization in the skin
Synchrotron SAXS/WAXS analysis can effectively profile drug crystallization in deeper skin layers without pre-treatment, improving drug delivery and safety.
Drug-drug co-crystallization presents a new opportunity for the development of stable vitamins.
Drug-drug co-crystallization offers a new opportunity for the development of stable vitamins with different physicochemical stabilities, offering a potential molecular level combination drug approach.
Challenges and Progress in Nonsteroidal Anti-Inflammatory Drugs Co-Crystal Development
Co-crystal innovation offers potential for safer, greener non-steroidal anti-inflammatory drugs, but faces challenges in selecting co-formers and developing methods.
Lyotropic liquid crystal systems in drug delivery.
Lyotropic liquid crystal systems, such as reversed cubic and hexagonal mesophases, offer unique microstructures and physicochemical properties for sustained release of bioactive molecules in drug delivery applications.
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