Multi-component forms of the 2nd generation H1 receptor antagonist drug, Bilastine and its enhanced physicochemical characteristics.

Bilastine (BIL) is a novel 2nd generation antihistamine medication is used to treat symptoms of chronic urticaria and allergic rhinitis. However, its poor solubility limits its therapeutic efficacy. In order to enhance the physicochemical characteristics of BIL, various molecular adducts of BIL (Salt, hydrate and co-crystal) were discovered in this study using two distinct salt-formers: Terephthalic acid (TA), 2,4-Dihydroxybenzoic acid (2,4-DHBA), and three nutraceuticals (Vanillic Acid (VA), Hydroquinone (HQN) and Hippuric acid (HA)). Various analytical methods were used to examine the synthesised adducts, including Powder X-Ray Diffraction (PXRD), Single Crystal X-ray Diffraction (SCXRD), and thermal analysis (Thermogravimetric analysis (TGA) and Differential Scanning Calorimetry (DSC)). Single-crystal X-ray diffraction (SCXRD) studies avowed that the architectures of the molecular adducts are maintained in the solid state by an array of strong (N+H⋯O-, NH⋯O, OH⋯O) and weak (CH⋯O) hydrogen bonds. Additionally, a solubility test was performed to establish the in vitro release characteristics of newly synthesised BIL adducts and it observed that most of the molecular adducts exhibit higher rates of dissolution in comparison to pure BIL; in particular, BIL.TA.HYD showed the highest solubility and the fastest rate of dissolution. Moreover, experiments on flux permeability and diffusion demonstrated that the BIL.TA.HYD and BIL.VA salts had strong permeability and a high diffusion rate. In addition, the synthesized adduct's stability was assessed at 25 °C and 90 % ± 5 % relative humidity, and it was found that all the molecular salts were stable and did not undergo any phase changes or dissociation. The foregoing result leads us to believe that the newly synthesized molecular adducts' increased permeability and solubility will be advantageous for the creation of novel BIL formulations.

Binary to ternary drug-drug molecular adducts of the antihypertensive drug ketanserin (KTS) with advanced physicochemical properties.

Focusing on a reliable supramolecular synthon approach, novel molecular salts of the antihypertensive medication ketanserin (KTS) with aromatic carboxylic acid derivatives (benzoic acid (BA), 2-hydroxybenzoic acid (2-HBA), and 2,5-dihydroxybenzoic acid (2,5-DHBA)) are reported. Binary salts of KTS with the respective salt former were obtained via solvent-assisted grinding followed by solution crystallization. Salt production was confirmed through crystal structure investigations that revealed proton transfer from the carboxylic acid group of the salt former to the piperidine nitrogen atom of KTS. A rigorous investigation of the crystal packing of novel binary salts of KTS inspired the construction of ternary adducts, and a ternary crystalline product was subsequently identified using milrinone (MLN), another cardiotonic drug. According to our knowledge, this is the first instance of a dual-drug ternary co-crystal combining both antihypertensive drugs. In order to evaluate the impacts of co-crystallization on the in vitro release behaviour of binary and ternary adducts, solubility tests for the cocrystal were carried out under a variety of physiological pH conditions. The results indicate that, in contrast to the parent drug and binary adducts, the solubility rate of the ternary adducts is significantly increased. Finally, the stability of the synthesised adduct was evaluated under a range of conditions, including temperature (40 ± 1 °C), humidity (90% ± 5% RH, 25 °C) and various solvents media, and it was established that they have good stability. We anticipate that the present findings will work with a wide range of medication combinations, providing a potential new approach to create multi-drug systems for cardiovascular disease.

Recent Advances in Pharmaceutical Cocrystals: From Bench to Market.

The pharmacokinetics profile of active pharmaceutical ingredients (APIs) in the solid pharmaceutical dosage forms is largely dependent on the solid-state characteristics of the chemicals to understand the physicochemical properties by particle size, size distribution, surface area, solubility, stability, porosity, thermal properties, etc. The formation of salts, solvates, and polymorphs are the conventional strategies for altering the solid characteristics of pharmaceutical compounds, but they have their own limitations. Cocrystallization approach was established as an alternative method for tuning the solubility, permeability, and processability of APIs by introducing another compatible molecule/s into the crystal structure without affecting its therapeutic efficacy to successfully develop the formulation with the desired pharmacokinetic profile. In the present review, we have grossly focused on cocrystallization, particularly at different stages of development, from design to production. Furthermore, we have also discussed regulatory guidelines for pharmaceutical industries and challenges associated with the design, development and production of pharmaceutical cocrystals with commercially available cocrystal-based products.