Pharmaceutical cocrystals offer a versatile approach to enhancing the properties of drug compounds, making them an important tool in drug formulation and development by improving the therapeutic performance and patient experience of pharmaceutical products. The prediction of cocrystals involves using computational and theoretical methods to identify potential cocrystal formers and understand the interactions between the active pharmaceutical ingredient and coformers. This process aims to predict whether two or more molecules can form a stable cocrystal structure before performing experimental synthesis, thus saving time and resources. In this review, the commonly used cocrystal prediction methods are first overviewed and then evaluated based on three criteria: efficiency, cost-effectiveness, and user-friendliness. Based on these considerations, we suggest to experimental researchers without strong computational experiences which methods and tools should be tested as a first step in the workflow of rational design of cocrystals. However, the optimal choice depends on specific needs and resources, and combining methods from different categories can be a more powerful approach.
20 June 2022 in International Journal of Pharmaceutics
Cocrystals have been extensively used to improve the physicochemical properties and bioavailability of active pharmaceutical ingredients. Cocrystals of anti-tuberculosis medications are among those commonly reported. This review provides a summary of the tuberculosis antibiotic cocrystals reported in the literature, providing the main results on current tuberculosis medications utilized in cocrystals. Moreover, anti-tuberculosis cocrystals limitations and advantages are described, including evidence for enhanced solubility, stability and effect. Opportunities to enhance anti-tuberculosis medications and fixed dose combinations using cocrystals are given. Several cocrystal pairs are suggested to enhance the effectiveness of anti-tuberculosis drugs.
Drug–drug cocrystals are formulated to produce combined medication, not just to modulate active pharmaceutical ingredient (API) properties. Nano-crystals adjust the pharmacokinetic properties and enhance the dissolution of APIs. Nano-cocrystals seem to enhance API properties by combining the benefits of both technologies. Despite the promising opportunities of nano-sized cocrystals, the research at the interface of nano-technology and cocrystals has, however, been described to be in its infancy. In this study, high-pressure homogenization (HPH) and high-power ultrasound were used to prepare nano-sized cocrystals of 4-aminosalysilic acid and sulfamethazine in order to establish differences between the two methods in terms of cocrystal size, morphology, polymorphic form, and dissolution rate enhancement. It was found that both methods resulted in the formation of form I cocrystals with a high degree of crystallinity. HPH yielded nano-sized cocrystals, while those prepared by high-power ultrasound were in the micro-size range. Furthermore, HPH produced smaller-size cocrystals with a narrow size distribution when a higher pressure was used. Cocrystals appeared to be needle-like when prepared by HPH compared to those prepared by high-power ultrasound, which had a different morphology. The highest dissolution enhancement was observed in cocrystals prepared by HPH; however, both micro- and nano-sized cocrystals enhanced the dissolution of sulfamethazine.
Onychomycosis is a disease that affects many adults, whose treatment includes both oral and topical therapies with low cure rates. The topical therapy is less effective but causes fewer side effects. This is why the development of an effective, easy to apply formulation for topical treatment is of high importance. We have used a nanotechnological approach to formulate Pickering emulsions (PEs) with well-defined properties to achieve site-specific delivery for antifungal drug combination of tioconazole and Melaleuca alternifolia essential oil. Silica nanoparticles with tailored size and partially hydrophobic surface have been synthesized and used for the stabilization of PEs. In vitro diffusion studies have been performed to evaluate the drug delivery properties of PEs. Ethanolic solution (ES) and conventional emulsions (CE) have been used as reference drug formulations. The examination of the antifungal effect of PEs has been performed on Candida albicans and Trichophyton rubrum as main pathogens. In vitro microbiological experimental results suggest that PEs are better candidates for onychomycosis topical treatment than CE or ES of the examined drugs. The used drugs have shown a significant synergistic effect, and the combination with an effective drug delivery system can result in a promising drug form for the topical treatment of onychomycosis.
This study presents a reproducible and scalable method for synthesizing silica nanoparticles (SNPs) with controlled sizes below 200 nm, achieved by systematically varying three key reaction parameters: ammonium hydroxide concentration, water concentration, and temperature. SNPs with high monodispersity and controlled dimensions were produced by optimizing these factors. The results indicated a direct correlation between ammonium hydroxide concentration and particle size, while higher temperatures resulted in smaller particles with increased polydispersity. Water concentration also influenced particle size, with a quadratic relationship observed. This method provides a robust approach for tailoring SNP sizes, with significant implications for biomedical applications, particularly in drug delivery and diagnostics. Using eco-friendly solvents such as ethanol further enhances the sustainability and cost-effectiveness of the process.