Recent Progress in the Oral Delivery of Therapeutic Peptides and Proteins: Overview of Pharmaceutical Strategies to Overcome Absorption Hurdles.

Purpose: Proteins and peptides have secured a place as excellent therapeutic moieties on account of their high selectivity and efficacy. However due to oral absorption limitations, current formulations are mostly delivered parenterally. Oral delivery of peptides and proteins (PPs) can be considered the need of the hour due to the immense benefits of this route. This review aims to critically examine and summarize the innovations and mechanisms involved in oral delivery of peptide and protein drugs. Methods: Comprehensive literature search was undertaken, spanning the early development to the current state of the art, using online search tools (PubMed, Google Scholar, ScienceDirect and Scopus). Results: Research in oral delivery of proteins and peptides has a rich history and the development of biologics has encouraged additional research effort in recent decades. Enzyme hydrolysis and inadequate permeation into intestinal mucosa are the major causes that result in limited oral absorption of biologics. Pharmaceutical and technological strategies including use of absorption enhancers, enzyme inhibition, chemical modification (PEGylation, pro-drug approach, peptidomimetics, glycosylation), particulate delivery (polymeric nanoparticles, liposomes, micelles, microspheres), site-specific delivery in the gastrointestinal tract (GIT), membrane transporters, novel approaches (self-nanoemulsifying drug delivery systems, Eligen technology, Peptelligence, self-assembling bubble carrier approach, luminal unfolding microneedle injector, microneedles) and lymphatic targeting, are discussed. Limitations of these strategies and possible innovations for improving oral bioavailability of protein and peptide drugs are discussed. Conclusion: This review underlines the application of oral route for peptide and protein delivery, which can direct the formulation scientist for better exploitation of this route.

Implementation of Quality by Design in the Formulation and Development of Nanocarrier-Based Drug Delivery Systems.

Quality by design (QbD) has recently fascinated researchers for utilizing it in various arenas of pharma trends. By overcoming the conventional process, QbD prevents the risk of errors caused by the 'guess and by god approach'. This framework fosters profound knowledge of product and process quality by implying sound science and risk assessment strategies. The virtue of QbD leads to the collaborative contribution to pharmaceutical industrialists and satisfies the regulatory bodies. Additionally, leading to rapid production, saves time and expenditure, tremendous versatility, provides immense knowledge, improves robustness, higher consistency, reduces user's dilemma, decreases certainty of failure, declining inter-batch variation in pharmaceutical development. In this ever-increasing continuous production world, regulatory organizations such as the U.S. Food & Drug Administration and the International Conference on Harmonization recommend Q8 to Q14 guidelines in order to obtain the desired quality product. This review extensively discusses on various approaches of QbD for the pharmaceutical development of nano-carrier drug delivery systems. Additionally, QbD's applications in process and analytical method development techniques are documented.