How Physiological Pharmaceutics Can Help Overcome Barriers To Drug Absorption
Drug absorption is the process by which a drug enters the bloodstream from the site of administration. It is a crucial factor that determines the efficacy, safety, and duration of action of a drug. However, drug absorption is not always easy to achieve, as there are many biological barriers that can prevent or reduce the amount of drug that reaches the systemic circulation.
Physiological pharmaceutics is a branch of pharmaceutical science that studies how the biological environment affects the performance of drugs and dosage forms. It aims to design new delivery systems that can overcome the body's barrier mechanisms, which have evolved to exclude foreign material. By understanding the anatomy, physiology, and biochemistry of different organs and tissues, physiological pharmaceutics can tailor the drug formulation to suit the specific needs and challenges of each route of administration.
In this article, we will review some of the main barriers to drug absorption that physiological pharmaceutics can help overcome, focusing on the oral, transdermal, nasal, pulmonary, and vaginal routes.
Oral Drug Absorption
The oral route is the most common and convenient way of administering drugs. However, it also poses many challenges for drug absorption, such as:
The acidic environment of the stomach, which can degrade or inactivate some drugs.
The enzymatic activity of the saliva and the gastrointestinal fluids, which can metabolize or modify some drugs.
The mucus layer and the epithelial cells that line the gastrointestinal tract, which can act as physical and biochemical barriers to drug diffusion.
The first-pass metabolism by the liver, which can reduce the bioavailability of some drugs before they reach the systemic circulation.
The variability in gastric emptying and intestinal motility, which can affect the rate and extent of drug absorption.
Physiological pharmaceutics can help overcome these barriers by designing dosage forms that can:
Protect the drug from degradation or inactivation by using enteric coatings, microencapsulation, or complexation.
Enhance the solubility and dissolution of poorly water-soluble drugs by using techniques such as micronization, nanosizing, solid dispersion, or cyclodextrin inclusion.
Increase the permeability of drugs across the intestinal epithelium by using permeation enhancers, such as surfactants, fatty acids, chitosan, or cyclodextrins.
Avoid or reduce the first-pass metabolism by using prodrugs, liposomes, nanoparticles, or targeting moieties that can deliver the drug directly to the systemic circulation or specific tissues.
Control or modulate the release of drugs in response to physiological stimuli, such as pH, enzymes, or pressure.
Transdermal Drug Absorption
The transdermal route is an alternative way of delivering drugs through the skin. It has several advantages over oral administration, such as:
Avoiding the first-pass metabolism and gastrointestinal side effects.
Providing a sustained and controlled release of drugs.
Improving patient compliance and convenience.
However, transdermal drug absorption also faces many barriers, such as:
The stratum corneum, which is the outermost layer of the skin and consists of dead keratinocytes embedded in a lipid matrix. It is highly impermeable to most drugs and acts as a rate-limiting step for transdermal delivery.
The viable epidermis and dermis layers, which contain blood vessels, lymphatics, nerves, hair follicles aa16f39245