Objectives In a short approach, we want to present the improvements that have recently been done in the world of new solid forms of known active pharmaceutical ingredients (APIs). The different strategies will be addressed, and successful examples will be given. Key findings This overview presents a possible step to overcome the 10-15 years of hard work involved in launching a new drug in the market: the use of new forms of well-known APIs, and improve their efficiency by enhancing their bioavailability and pharmacokinetics. It discusses some of the latest progresses. Summary We want to present, in a brief overview, what recently has been done to improve the discovery of innovative methods of using well-known APIs, and improve their efficiency. Multicomponent crystal forms have shown to be the most promising achievements to accomplish these aims, by altering API physicochemical properties, such as solubility, thermal stability, shelf life, dissolution rate and compressibility. API-ionic liquids (ILs) and their advantages will be briefly referred. An outline of what has recently been achieved in metal drug coordination and in drug storage and delivery using bio-inspired metal-organic frameworks (BioMOFs) will also be addressed. PreambleIn the last decade, several approaches to attain multicomponent pharmaceutical forms have been used and different kinds have been obtained. The most notorious cases are undoubtedly co-crystals and molecular salts [1] and their design, using crystal engineering principles, strategic and synthetic approaches have been the subject of different reviews.[2-5] Also, their characterization and implications for regulatory control and intellectual property protection have been presented and discussed. Here, we go one step forward and taking into account the recent definition of pharmaceutical co-crystal; from the published outcome of the Indo-US bilateral meeting in 2012 [6] and the FDA guidance draft for co-crystals, [7] which classifies co-crystals as 'dissociable API-excipient molecular complexes' where the co-former is the excipient, we call pharmaceutical companies' attention to the fact that following FDA rules, co-crystals can be treated as drug product intermediate, offering the potential of abbreviated new drug application rather than the full new drug application. This can be looked upon as not only a prompt process involving fewer risks, but also a less cost-effective process. Different steps have also been given to enhance drug properties through API metal coordination, generating metallodrugs and metallopharmaceuticals and more recently bio-inspired metal-organic frameworks (BioMOFs) for drug storage and controlled delivery. Here, we briefly present and discuss some of the recent published work, giving examples where the proposed routes proved to be beneficial.
In the last decades the electroplating industry has paid a great deal of attention to alternative electrodeposition baths with lower environmental and health impacts. In the case of black chromium coatings, usually obtained from water-based hexavalent chromium Cr(VI) solutions, the search for aqueous alternatives has been centered on Cr(III) formulations, while attempts using non-aqueous media, including ionic liquids (ILs) solutions, have been restricted by the lack of solubility of Cr(II) and Cr(III) salts in these solvents. Literature is scarce, even though electrodeposition of Cr has been reported from an ionic liquid analogue solution consisting of choline chloride and hexahydrated chromium salt, either as an amorphous [1] or a nanocrystalline film [2]. In the present paper, the electrodeposition of black chromium thin films from a solution of trivalent chromium in 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIm][BF 4 ]) is reported. Electrolyte preparation, electrochemical characterization of both the liquid and the electrodeposition process and the electrodeposition experiments, were all carried out under argon atmosphere in a glove box with a gas purification system capable of ensuring water and oxygen contents below 2 ppm. AISI 304 stainless steel was chosen as a substrate material. Typical cyclic voltammetry studies, performed from -2V to +2V vs Pt QRE at a scan rate of 50 mVs -1 , indicated redox features associated to Cr species and a crossover loop indicating a nucleation process, defining the electrochemical window for effective electrodeposition. Continuous and homogenous films with a granular morphology were obtained for deposition times up to 1 hour at -1.5V (Pt). Experimental current density-time transients obtained by chronoamperometry will be discussed in the light of available models for nucleation and growth. Experimental results showed good agreement with theoretical values indicating that nucleation of black chromium films in [BMIm] [BF 4 ] is instantaneous and under diffusion control.
Mechanochemistry is a powerful and environmentally friendly synthetic technique successfully employed in different fields of synthetic chemistry. Application spans from organic to inorganic chemistry including the synthesis of coordination compounds. Metal-organic frameworks (MOFs) are a class of compounds with numerous applications, from which we highlight herein their application in the pharmaceutical field (BioMOFs), whose importance has been growing and is now assuming a relevant and promising domain. The need to find cleaner, greener and more energy and material-efficient synthetic procedures led to the use of mechanochemistry into the synthesis of BioMOFs.
The development of metal–organic frameworks (MOFs) for bioapplications has gained great relevance over the last few years, mainly due to their potential as drug carriers and/or imaging agents. Although the bioactive azelaic acid has also been widely used as an antibacterial and anti-inflammatory drug, it presents low solubility, so of utmost importance is the development of more soluble formulations with sustained activity. In this contribution, we prove that new azelaic acid-based metal biomolecule frameworks (BioMOFs) are a viable pathway to achieve this goal. Therefore, five novel MOFs were prepared by a simple, low-cost, and environmentally friendly mechanochemical approach, combining azelaic acid with endogenous cations (i.e., K+, Na+, and Mg2+): [K2(H2AZE)(AZE)] (1), [Na4(HAZE)4] (2), [Na2(AZE)(H2O)] (3), and two different polymorphic forms of [Mg(AZE)(H2O)3] (4) and (5) (where H2AZE - neutral azelaic acid; HAZE - mono-deprotonated azelaic acid; AZE - di-deprotonated azelaic acid). After full structural characterization using single-crystal X-ray diffraction data and other complementary standard solid-state techniques, their thermal and moisture stabilities as well as aqueous solubility were assessed. Finally, their antibacterial activity was evaluated against two Gram-positive bacteria (Staphylococcus aureus and Staphylococcus epidermidis), commonly present on the skin. All MOF materials exhibit good stability and higher solubility than azelaic acid. In addition, BioMOF 1 has shown good antibacterial activity both at pH 5 and 6.5. Thus, 1 has shown to be a promising candidate to further develop new topical formulations of H2AZE.
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