Influence of excipients on drug absorption via modulation of intestinal transporters activity

Abstract

O ne of the major factors affecting oral drug bioavailability is the activity of intestinal transport proteins, particularly for the drugs that undergo absorption by active transport mechanism. Many of the active pharmacological agents and the excipients used in their formulation are reported to modulate the activity of these transporters thereby either enhancing or decreasing the drug absorption and its systemic availability. These excipients are considered pharmacologically "inert" and have been used since years in pharmaceutical formulations. Appreciable interest is developing on the data demonstrating the role of excipients in altering the drug absorption across the intestine. Careful selection of the excipients thus is very important. A correctly chosen excipient can enhance the drug bioavailability and thus its therapeutic efficacy without increasing its dose. For locally acting drugs having systemic side effects, a proper excipient could lead to a decrease in its systemic absorption, thus reducing its side effects. This review focuses on the current findings of the excipients identified to modulate the activity of transporters, their mechanism of modulating the transporter's activity and various formulation strategies using these excipients to enhance drug absorption.

Comparisons between a self‐microemulsifying system and lipid nanoparticles of oxyresveratrol on the physicochemical properties and Caco‐2 cell permeability

“…Higher oil content was required for any higher drug loading capacity and also produced a lower proportion of the surfactant phase. However, a high proportion of the surfactant phase allowed for good characteristics of the formulations and also improved drug absorption . Therefore, the SMEDDS containing 45% of the C90 oil and surfactant phase (45% CRH40 and 10% Tw80) were formulated to compare with the lipid nanoparticle systems (Table ).…”

“…In this study, the % surfactant phase (55% w/w) of the SMEDDS was about ten times greater than for the lipid nanoparticles system (5.625% w/w). Considering that Tw80 can be toxic, the specific mixture of Tw80 and other surfactant types might cause the difference . In addition, the greater % of Tw80 in the SMEDDS (10% w/w) than in the nanoparticles systems (3.75% w/w) indicated that the more toxic nature of the former system was most likely due to the concentration of the cytotoxic properties of the surfactants .…”

“…The oil used in the SMEDDS is generally known to be safe for oral delivery. However, the C90 oil which contained PG esters group implied they could be cytotoxic on the Caco‐2 cells at high concentrations . Meanwhile, the Com888 solid lipid, long chain glyceride, and LCC oil, medium chain triglyceride, commonly used in NLC were compatible to the intestinal cells because its structure was similar to the physiological lipids of the body.…”

“…Finally, the compound formulated as the solid lipid and oily formulations was absorbed into the lymphatic pathway before reaching the systemic circulation . Moreover, the inhibitory activities on the efflux mediated transporter(s) and modulation of the tight junction by the surfactants in the lipid formulations resulted in promoting oral absorption . These potential mechanisms for the lipid‐based formulations facilitated oral delivery.…”

Pharmacodynamics Effect of Methylprednisolone Tablets on the Serum Concentration of Annexin A1: In Vivo Comparative Study Between Generic and Innovator Drug

“…In addition, some excipients in the formulation are also reported to alter the activity of intestinal transport proteins and thus can influence the absorption of the drug molecules. Therefore, the pharmaceutical excipients can alter the bioavailability and, in turn, the pharmacological effect of the drugs [29].…”