An overview of the alarming impediments encountered while establishing an apposite IVIVC of nanomedicines necessitated its regulatory approval

For the past three decades, the principle of nanotechnology has been widely employed to develop pharmaceuticals and bio-pharmaceuticals that are successful for many disease therapies. Several commercially available approved nanomedicines are more efficacious than conventional dosage forms and successfully manage many diseases. The patient's well-being and the certainty to resolve the unresolved challenges of medical science became realistic due to the advent of novel pharmaceutical products based on nanotechnology. These benefits are observed as in humans, the absorption profile of a drug fabricated into nanoparticles varies widely with that of its conventional dosage forms mainly due to the physicochemical modifications and results in highly deviating in-vitro and in-vivo data for the same drug when administered as nanoparticles. The researchers and regulators must frame new guidelines that guide the pharmaceutical industry to develop novel nanomedicines that conform to the desired safety and efficacy. The nanoparticles translational research conducted at the academic level is mainly developing, and the scale-up techniques of the clinically approved nanomedicines are yet to be optimized from the perspective of the manufacturer as well as the regulatory authorities. The IVIVC serves as a reference document that reinforces the pharmaceutical industries to substantiate and expedite the credentials of an oral dosage form about the New Drug Application (NDA), Abbreviated New Drug Application (ANDA), or Antibiotic Drug Application (AADA). A poor in-vitro in-vivo correlation (IVIVC) marks a constraint factor, which declines the clinical approval for nanomedicine and its commerce. As on date, neither any specific regulatory guidelines nor any specific calculation methods have been drafted that facilitate the determination of the IVIVC for nanomedicine. Most of the research scientists involved in developing nano/micro/macro formulations do not consider IVIVC an essential criterion. Therefore, a lag in assessing the formulation of assured quality for the next phase happens in the drug development cycle, which terminates the formulation mostly at its pilot scale rather than for its succession as a viable market product. In the pharmaceutical industries, the necessity for IVIVC has been expanded to a greater extent, and a strong IVIVC is recommended to approve the developed nanoformulations of poorly soluble drugs; thus, an appropriate IVIVC model shall be established to expedite the regulatory process for easy and rapid market approval of the developed nanomedicine. The objective of the present review includes examining and considering the various associated factors involved in the development of an IVIVC model for nanomedicine, viz., Physico-chemical characteristics and bio-pharmaceutical factors (Formulation and physiological factors); to deliberate on the pros and cons of the various in-vitro dissolution study methods with due consideration to the inter-subject variations and use the suitable approach to exactly predict the in-vivo absorption for obtaining a good IVIVC. This review prominently emphasizes the critical factors associated with the regulatory approval of nanomedicines and further explores the various research works pursued, abiding by the current international regulatory guidelines.