Drug solubility refers to the properties within a drug (solute), allowing it to dissolve in a particular solution (solvent), which in this case is the human body’s digestive fluids.
These digestive fluids contain variable concentrations of enzymes, stomach acid, and bile accompanied by bacteria throughout the gastrointestinal tract (microbiome), which together help to break down ingested substances. The goal of drug solubility is to deliver a desired concentration of active pharmaceutical ingredients at a specific time during the digestive process for absorption into the body’s systemic circulation to achieve a particular effect.
Bioavailability
The Merck Manual defines bioavailability as “the extent and rate at which the active [components of a drug] enter systemic circulation, thereby accessing the site of action.”
Bioavailability depends primarily on certain properties of the dosage form, including:
aqueous solubility
drug permeability
dissolution rate
Dosage forms include pills, tablets, syrups, drinks, or capsules, among others. Aspects of drug design and manufacture influence these dosage form properties.
Oral bioavailability also depends on how the individual metabolizes and absorbs the ingested drug. This depends on several factors, such as:
patient age and disease status
first-pass metabolism
pre-systemic metabolism
gastric emptying rate
intestinal transit time
blood flow at the absorption site
gastrointestinal contents
susceptibility to efflux mechanisms contributing to drug resistance
How 3D Printing Improves Drug Solubility and Bioavailability
Laxxon Medical’s 3D printing technology has enabled the customization of oral drug delivery through the specific selection of more effective formulations, internal structural designs, and geometric shapes that improve drug solubility and precise timing of drug release.
Specific Materials Affect Drug Solubility
Drug developers in the 3D printing industry often use polyvinyl alcohol (PVA), a soft, biodegradable polymer that dissolves quickly in water. The inherent properties that make PVA highly water soluble and increase biocompatibility in human tissues and fluids make it an effective material for the 3D printing of drugs.
Hypromellose (HPMC) is a hydrophilic polymer with specific thermal properties that impact drug decomposition. HPMC can be used as a coating for 3D printed tablets to enhance drug solubility through the inhibition of active pharmaceutical ingredient crystallization and maintenance of the stability of solid dispersions.
These are just two examples of materials that have been explored in 3D printing that affect drug solubility. Laxxon’s partnership with Evonik Industries provides access to a wide array of chemicals and polymers to explore their unique properties in terms of drug solubility and release profiles for 3D pharmaceutical printing. Access to a wider variety of printable materials enables an increased number of permutations for drug design and manipulation of individual drug solubility traits.
Precisely Timed Release of Active Pharmaceutical Ingredients Affects Drug Bioavailability
3D printing can separate incompatible ingredients through spatial arrangements of excipients using different and sometimes complex geometric shapes. 3D printing can also achieve precise release rates based on the shape and size of the printed dosage form.
The additive layering process of 3D printing allows drug manufacturers to select formulations that arrange active pharmaceutical ingredients in some layers and inert substances in other layers in such a manner as to alter the timing of dose release.
The specific distribution of active and inactive substances in these printed layers promotes a sequential release of these drug components. This sequential release can help the drug to effectively bypass first-pass metabolism functions by protecting layers of active drug substances with layers of inactive materials until the drug reaches a specific target area in the body for absorption into the systemic circulation.
Controlled drug release decreases fluctuations in the concentrations of active drug substances released into the body due to the manipulation of specific properties affecting oral drug solubility and timing of the release. Optimized release kinetics increases drug bioavailability with predictability and reproducibility during a specific therapeutic window.
Careful control of these factors influencing drug delivery also reduces the likelihood of side effects, such as drug toxicity associated with premature dosing or decreased drug efficacy due to missed doses.
An Example of How 3D Printing Can Improve Drug Efficacy
Controlled drug release mechanisms can be observed in a particular way in the extension of the therapeutic window of the drug, levodopa, used to treat Parkinson’s disease. This extended-release profile increases the bioavailability of levodopa to allow patients with advanced Parkinson’s disease to be able to move first thing in the morning after a long night’s sleep and prevent a side effect commonly called the freezing of gait.
Laxxon Medical is dedicated to engineering patented 3D pharmaceutical solutions which optimize products and benefit patients. Our goal is to establish SPID®-Technology as a manufacturing process that has the individual and the pharmaceutical partner in mind.