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Mitigating the Challenges of Oral Administration of Biologics



The number of physiological barriers present in the gastrointestinal tract is a major challenge that must be surmounted in other to achieve clinically relevant oral biologics delivery. A step in this direction includes recent advances in the design of drugs that make oral biologics possible.


Oral administration accrues the benefits of simplicity and familiarity when oral drugs are administered to patients making it the most preferred route. Early on the knowledge of medicines is described and represented through the oral route it is the first route of administration everyone encounters. The ease of access is also a concern when factors such as size, shape, surface and texture are considered. Solid oral presentations are more convenient for most patients making them particularly valuable especially when the target site is the gastrointestinal tract (GIT). The oral route is the best for making delivery in such treatment.


The gastrointestinal system of humans is highly evolved in mechanisms to enable break down of molecules of all sizes and absorption possible. Biologics are a group of large complex molecules that depend on their structure to engage with targets in other to achieve their therapeutic purpose. Administration of this molecule through the GI a system that functions to destroy it results in a significant number of challenges that must be overcome.

Protection of the molecule from breakdown is the first step required to ensure its purpose is achieved. This is because the GI tract contains a number of acids and enzymes for breaking down molecules. Next is the transport of these large molecules through the multiple layers of mucous and cells that line the GI tract in other to achieve systemic distribution of the molecule. An easier challenge is if the target of the molecule is the GI tract. The location of absorption is the last essential challenge that must be overcome and is more challenging depending on the nature of the protective mechanisms of the molecule.


Systematic bioavailability of a biologic administered orally is lesser compared to biologics administered through intravenous or subcutaneous routes. It is confirmed that less than 10 percent of orally administered those is systematically available. This however is because of the challenges outlined earlier which are absent in intravenous and subcutaneous administration. Improving bioavailability for oral biologics is of utmost importance and therefore great focus is on achieving this goal.


The concentration of a drug is maintained within the body until it makes impact on its target, the time required for this is termed as the half-life of the drug. Molecular structure, route of administration and duration over which the drug is administered can all play a significant impact in the clearance time. Essentially, a molecule ought to remain at a therapeutically relevant concentration at the target site for as long as necessary, this allows for optimum functioning leading to high quality results with limited dosing. Although certain instances require longer doses but the fewer the dosing and length of treatment the better. A number of instances to impact on the half-life of a drug do exist, one of such is in the molecular structure of the drug another instance is addition of excipients that delay its clearance time. This could be a molecule that binds to the drug and protects it from clearance examples include materials that transform from liquids to gels on entry into the body.


The rate of administration is another method to control the clearance of a drug. This may adopt formulation methods that slowly eliminate the drug or dissolve it over time or it might be a molecule that slowly releases the drug over longer time frames. The low bioavailability of biologics administered orally means a lower amount of drug gets into the system compared with other routes of administration. This means that whatever drug gets into systemic circulation is highly valuable and must be prevented from rapid clearance. Therapeutic bioavailability is the major focus of current research into orally administered biologics.


The molecules that are stable to enzymatic degradation, enteric coatings that protect the active ingredient and time the release of the payload and small molecule excipients that enhance the permeation of the drug through the mucus and epithelial layers of the GI system are the most commonly adopted approaches to address the barrier problems facing orally administered biologics. These approaches have been used both individually and in combination in hopes of protecting the biologic molecule and allowing it to pass into the circulatory or endocrine system.


There’s been poor improvement to develop and advance the bioavailability of orally administered biologics even though the science of these approaches has evolved over the past several decades. As a result, many studies are now looking into alternative approaches. One method is the use of mechanical penetration enhancers rather than chemicals example is the use of syringes to deliver biologics, it may be possible to adopt this method in the administration of oral biologics. Pre-clinical models for delivery of tiny arrays of needles within capsules have been proposed and demonstrated by several groups. Other methods include jet injectors that can force the liquid drug through the GI tissue without the use of a needle. These systems can become complex and there is still a lot to demonstrate. One particular focus of interest is in the method of infestation of certain pathogens and how they are able to survive these harsh conditions before successfully infecting the host. Understanding this approach may provide new ideas on method of delivery.


The development of dosage forms that optimize patient convenience while also ensuring successful delivery with the most efficient therapeutic outcome. Large molecules present the highest challenges of oral delivery. Addressing GI targets directly is a major concern as this will improve treatment of diseases that directly infect the GI as well as systemically. The aim of this is to maximize the therapeutic benefits while minimizing the systemic side-effects all in stable dosage form convenient for patients.

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