Abstract
Conclusions from previously reported articles have revealed that many commonly used pharmaceutical excipients, known to be pharmacologically inert, show effects on drug transporters and/or metabolic enzymes. Thus, the pharmacokinetics (absorption, distribution, metabolism and elimination) of active pharmaceutical ingredients are possibly altered because of their transport and metabolism modulation from the incorporated excipients. The aim of this review is to present studies on the interaction of various commonly-used excipients on pre-systemic metabolism by CYP450 enzymes. Excipients such as surfactants, polymers, fatty acids and solvents are discussed. Based on all the reported outcomes, the most potent inhibitors were found to be surfactants and the least effective were organic solvents. However, there are many factors that can influence the inhibition of CYP450, for instance type of excipient, concentration of excipient, type of CYP450 isoenzyme, incubation condition, etc. Such evidence will be very useful in dosage form design, so that the right formulation can be designed to maximize drug bioavailability, especially for poorly bioavailable drugs.
Highlights
The most popular route for drug delivery is oral administration because of pain avoidance, ease of ingestion, patient compliance and versatility of drug candidates
One potential explanation based on the results is that, at high concentration, polyunsaturated fatty acids disrupt the microsomal membrane, which prevents the binding of the drug to the active site of the CYP450 enzyme [99]
Pharmaceutical excipients play an important role in pharmaceutical products and are often presumed to be pharmacologically inert
Summary
The most popular route for drug delivery is oral administration because of pain avoidance, ease of ingestion, patient compliance and versatility of drug candidates. The manufacturing for oral drug delivery systems is less expensive as the production process is simple and there are no requirements for sterile conditions [1]. Despite all the benefits of oral delivery, poor bioavailability of oral formulations is a limiting factor that can alter the efficacy and therapeutic effect [3]. Various factors are contributing to low oral bioavailability including physiological factor, high gastric emptying time, the effect of food, intestinal barrier and enzymatic degradation of drugs (Table 1). First-pass metabolism is one of the key factors responsible for poor bioavailability. The extensive metabolism of drugs prior to reaching the systemic circulation is known as the first-pass metabolism. The drug is metabolized in the liver before reaching systemic circulation, resulting in a low available concentration at the intended target site (Figure 1). Due to insufficient plasma concentrations, the bioavailability of the drug is significantly reduced and a high dose of the drug is required [4]
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