Bioavailability Enhancement Strategies: Basics, Formulation Approaches and Regulatory Considerations

Abstract

Poor solubility remains a major challenge for pharmaceutical industry, which is now considered to be an area of prime importance in the field of biomedical research. Approximately 40% new molecular entities (NMEs) synthesized in pharmaceutical R with advanced combinatorial chemistry and computer aided drug designing (CADD) approaches suffer from poor solubility and bioavailability related issues. Apart from these presence of intestinal tight junctional epithelial cells, transporters and enzymatic barriers further reduces the oral absorption of drugs. Implication of the novel lipid based nanocarriers and nanomaterials like dendrimers and carbon nanotubes as a delivery system can effectively enhance the oral bioavailability of drugs by breaching the barriers, and resolve all critics related to solubility and bioavailability. Thus prime objectives of this review are to give in-depth knowledge and critical appraisal on the barriers for poor oral bioavailability of drugs, along with various novel formulation approaches used for bioavailability enhancement such as lipid based formulations, nanosizing techniques, complexation with polymers and nanomaterials like dendrimers, carbon nanotubes, and penetration enhancers. Also it gives a brief account on in vitro, in vivo screening methods used for assessment of oral bioavailability, and regulatory considerations for the approval.

Solid self-nanoemulsifying drug delivery system (S-SNEDDS) for oral delivery of glimepiride: development and antidiabetic activity in albino rabbits

“…In these drugs, dissolution of the drug is the rate limiting step in the absorption process. To triumph over these obstacles, numbers of formulation approaches are reported including the use of surfactants (Allaboun et al, 2003;Balakrishnan et al, 2004;Chakraborty et al, 2009), lipids (Yeap et al, 2013), permeation enhancers (Burcin et al, 2010;Beg et al, 2011), formation of salt (Li et al, 2005;Serajuddin, 2007), co-crystallization (Shan & Zaworotko, 2008;Qiao et al, 2011;Chadha et al, 2012), solid dispersions (Serajuddin, 1999), inclusion complexes with cyclodextrins and modified cyclodextrins (Miyake et al, 2000;Veiga et al, 2000;Wang et al, 2000;Bannwart et al, 2001;Carrier et al, 2007;Gamsiz et al, 2010a,b;Gamsiz et al, 2011;Badr-Eldin et al, 2008;Kumar et al, 2013), nanosuspensions (Patravale et al, 2004), and colloidal vesicles like liposomes (Nazzal et al, 2002a;Manconi et al, 2013;Yang et al, 2013), and niosomes (Khazaeli et al, 2007;Bayindir & Yuksel, 2010;SezginBayindir et al, 2013;Jin et al, 2013) In modern years, self-nanoemulsifying drug delivery systems (SNEDDS) are the most popular and commercially feasible lipid-based formulation approach for improving oral bioavailability of poorly water soluble and lipophilic drugs (Pouton, 2006;Date, 2007;Shweta et al, 2011). SNEDDS are precisely defined as an isotropic multi-component drug delivery systems composed of a synthetic or natural oil, surfactant, and co-surfactant that have a unique ability of forming fine oil in water micro-or nano-emulsion upon mild agitation followed by dilutio...…”

How nanotechnology can enhance docetaxel therapy

“…Owing to lipid materials and biomimetic structure, lipid-based nanoformulations have been widely used for DTX delivery as they offer good biocompatibility, effectively increasing DTX's water solubility, significantly improve drug membrane permeability, and allow sustained drug release. 49,50 Table 2 summarizes some representative lipid-based nanoformulations for DTX delivery that have been recently reported.…”

Novel dietary lipid-based self-nanoemulsifying drug delivery systems of paclitaxel with p-gp inhibitor: implications on cytotoxicity and biopharmaceutical performance

“…In the past few years, oral delivery of anticancer drugs have paid considerable attention over the conventional chemotherapeutic approaches for attaining maximal therapeutic efficacy, reducing the side-effects and improving the patient compliance [1][2][3]. However, oral delivery of anticancer drugs possess major challenge to the pharmaceutical scientists owing to multiple problems such as poor aqueous solubility, extensive hepatic first-pass effect, poor gastric stability and efflux by P-gp transporters, all leading to poor oral bioavailability and sub-maximal therapeutic response [4].…”