Editorial [Hot Topic: New Paradigms in Drug Formulation and Phytotherapeutics (Guest Editor: Shyam M. Rele)]

Drug development has become increasingly complex, time consuming and expensive. As a result there is an increased focus on making clinically established drugs with enhanced therapeutic performance in terms of efficacy, safety and improved patient compliance. This has led to a paradigm shift not only in drug discovery programs but also in drug formulation technology. In this context, the present issue highlights some of the recent trends with emphasis on new formulation technologies for active pharmaceutical ingredients (API's) along with developments in phytopharmaceutical research. The discovery and development of quality drug leads and clinical candidates, that will eventually become novel marketable drugs, remains a significant challenge to pharmaceutical scientists. For numerous pharmacological reasons, many active compounds or new drug candidates face bioavailability issues due to poor aqueous solubility and are poorly absorbed when dosed orally creating a challenge to prepare formulations that maximize bioavailability and improve API delivery to the intended therapeutic target. The field of API formulations while maximizing exposure in early animal experimentation, so that the pharmacokinetics, pharmacodynamics and toxicological signals can be put into context with the biological response to specific targets, could play a critical role in assessing the biological properties of a molecule during drug discovery. Consequently, many biotech and pharma companies face barriers due to the failure of these otherwise-effective developmental compounds in the pre-clinical/clinical trials and are typically pulled out of the development cycle, further weakening the already dwindling drug pipelines. As a result there is an urgency to develop efficacious formulation methods that will integrate drug-like properties into the early stages of drug discovery advantageous to efficient and effective drug development and which will ideally reflect in critical issues of safety, pharmacokinetics and formulation in addition to in vivo performance. Recent trends indicate that pharmaceutical and biotech companies are looking to enhance the clinical efficacy of experimental as well as known compounds with poor bioavailability by generating homogeneous amorphous solid dispersions of API's in a polymer matrix that significantly improves the bioavailability profile of the active candidate drug by increasing both the dissolution rate and the free-drug concentration over the more typical crystalline forms of therapeutic candidates. In recent years several amorphous API's have been marketed as drug products. Examples include Accolate® (zafirlukast), Ceftin® (cefuroxime axetil), Accupril® (quinapril hydrochloride), and Rezulin® (troglitazone). Lilly's Humulin L® contains both amorphous and crystalline insulin to provide immediate and long-term effects. Design and development of rational amorphous API formulations that will have clinical significance is of paramount importance and will influence future drug discovery and optimization programs. Drug Discovery in current scenario has become unproductive to the point where the economic future of the industry is questionable. Moreover, problems with drug-resistant microorganisms, side effects of modern drugs, emerging diseases where no medicines are available in addition to existing patent expirations, the scientific community is experiencing difficulty in identifying new lead structures, templates and scaffolds in the finite world of chemical diversity. To push into the future, the R&D thrust in the pharmaceutical sector needs to be focused not only on the cost-effective development of new drugs and innovative processes and formulations for known/new drugs but also on the development of plant-based drugs/extracts through investigation of leads from the traditional systems of medicine which could provide the necessary impetus into the drug development process. While plants and marine organisms inherit a unlimited pool information, new molecules and medicines, drug discovery via integration of phytopharmaceutical research with modern medicine potentially offers an attractive strategy for faster, cheaper development and screening of alternative drug discovery platforms that could work more effectively and could therefore help address the growing need of large pharmas/biotech to fuel their diminishing pipelines. The use of powerful new technologies such as automated separation techniques and high-throughput screening can greatly facilitate intentional, focused and safe natural product drug discovery and help to rediscover the drug discovery process. However, though timetested evidences vouch immense therapeutic benefits for phytochemicals (plants, marine organisms, and nutraceuticals) and their formulations, several important issues are required to be resolved with rigorous guidelines of standardization, manufacture, quality control, and scientific research before successful implementation of these principles to present drug discovery methodologies. Additionally, clinical examination directed towards understanding the pharmacokinetics, bioavailability, efficacy, safety and drug interactions of newly developed phytodrugs and their formulations (extracts) are required to be carefully evaluated. Nevertheless, by looking at the historical trends in drug and medical developments, it is possible to understand how current drug development and formulation will benefit from this partnership to create an equitable system of health.