Key Takeaways

• Controlled-release drug delivery systems (CRDDS) supply medications within specific timeframes, using techniques like diffusion, dissolution, and osmotic control to produce reliable administration and improve patient compliance.
• These drug delivery systems come in a variety of forms, including parenteral (injectables like IV, IM, SQ), oral (tablets, capsules), transdermal (patches), and implants, all of which bypass the gastrointestinal system and hepatic first-pass metabolism to supply enhanced bioavailability and targeted efficacy.
• Some advanced controlled-release drug delivery systems use intelligent biomaterials, such as biodegradable polymers for implants and nanocarriers (liposomes, dendrimers) for targeted delivery, and current research is pursuing emerging opportunities in 3D printing and microfluidics.

Controlled-release drug delivery systems are incredibly beneficial for a range of medical conditions and applications, providing improvements over standard drug delivery systems. Conventional drug delivery can produce fluctuations in plasma drug levels, requiring frequent doses of the drug to be administered. Patient compliance can also be a problem, as well as reduced efficacy.

Using CRDDS approaches, however, can reduce the frequency of doses, prevent patient compliance issues, and produce 100% bioavailability, maintaining constant therapeutic blood levels.

Parenteral Controlled Delivery: Long-Acting Injectables (LAIs)

Parenteral delivery uses long-acting injectables to bypass the digestive track and first-pass metabolism, administering drugs that feature timed releases that can last from 1 week up to 1 year. Injectables can use intravenous (IV), intramuscular (IM), and subcutaneous (SQ) administration approaches.

These injections are easily syringable with 18- to 23-guage needles, offer positive stability characteristics, and are known for facilitating proven content uniformity. Their microsphere-based design makes them ideal for use with biodegradable polymers such as PLA, PLGA, and others.

Oral Controlled Delivery: Tablets and Capsules

Controlled-release drug delivery systems that use oral-intake methodologies, whether via tablets or capsules, are another common form used in medical applications. Delayed-release medications bypass deterioration normally imposed by stomach acid, pulse-release medications are designed to mimic standard biological rhythms, and osmotically controlled systems use laser-drilled holes in medication membranes to allow for steady absorption.

Many chronic conditions that require long-term medication administration use orally administered drugs, including diabetes, psychiatric conditions, heart problems, and more.

Transdermal Controlled Delivery: Patches and Implants

This form of drug delivery uses adhesive patches or implants to deliver predetermined doses of a medication via the skin and into the bloodstream. Different subsets of transdermal patches exist, including the drug-in-adhesive style that features the drug incorporated within the adhesive itself, the reservoir style which contains a secondary layer (a drug reservoir) that distributes the medication, the matrix style that features a semisolid matrix containing a drug solution, and the multilaminate style that features different layers of drugs.

Consumers are most familiar with these drug delivery systems through the prevalence of nicotine patches, but other options exist including fentanyl for severe pain and scopolamine for nausea and motion sickness.

Controlled Delivery Subprocesses

Biomaterials for Controlled Delivery: Biodegradable and Nonbiodegradable Systems

Various biomaterials aid in modulating the pharmacokinetics of a drug, including substances like polymers, peptides, and lipids. These biomaterials can be categorized as either biodegradable or nonbiodegradable in nature, with biodegradable being preferred since they are absorbed within the body and do not need to be removed. At Oakwood Labs, our long-acting injectables feature biodegradable polymers like polylactic acid (PLA), polylactic-co-glycolic acid (PLGA), and others.

Chemically and Water-Penetration-Controlled Implants

When it comes to implanted systems for controlled delivery, two key release mechanisms are used: chemically controlled systems and water-penetration or osmotic pressure-controlled systems.

Chemically controlled systems use biodegradable polymers via the methods of bulk erosion, which facilitates a breakdown throughout the material, and surface erosion, which features a breakdown only at the surface. Factors that can impact erosion include chain defects, configuration, and molecular weight.

Water-penetration-controlled implants, or osmotic pressure-controlled systems, on the other hand, use osmogens, moving a solvent from a lower concentration of solute toward a higher concentration across a semi-permeable membrane.

Stimuli-Responsive (Smart) Controlled Delivery Systems

Smart biomaterials respond to both internal and external stimuli, triggering or modulating a drug’s release. These stimuli can be categorized as chemical in nature, or physical, with chemical including aspects like pH, redox potential, and enzyme concentration, and physical including response to aspects like temperature, electric field, light, and more. Sensitivity to specific stimuli must be high since delivering excessive external stimuli could result in the damage of healthy tissues.

Nanocarriers: Targeted and Advanced Delivery

One emerging approach in the controlled drug delivery space is nanocarriers, which can offer improved bioavailability, sustained release action, and targeted delivery. Some of these nanocarriers include liposomes, which use enhanced permeability and retention (EPR) for targeting tumors, dendrimers, which feature a high surface area and symmetrical structure, and solid-lipid nanoparticles, ideal for use in the lungs and other parts of the body. Nanocarriers are also ideal for overcoming biological barriers, including crossing the blood-brain barrier.

FAQs on Controlled Release Types

What is the difference between a diffusion-controlled reservoir system and a monolithic matrix system?

A reservoir system contains the drug core covered by a thin membrane, allowing for easier achievement of zero-order release, maintaining a constant rate over time, but risking dose dumping if ruptured. Monolithic systems, on the other hand, have the drug dispersed throughout the matrix, making zero-order release difficult but eliminating the danger of dose dumping.

What essential structural components constitute a basic transdermal patch system?

A typical transdermal patch is composed of a backing film for protection, a drug layer (reservoir or drug-in-adhesive), a membrane to control the diffusion rate, an adhesive layer, and a release liner that is removed before application.

What were the key technologies of the various generations of controlled drug delivery systems?

The first generation, from the 1950s to the 1980s, focused on basic controlled release via dissolution, osmosis, diffusion, and ion exchange, accelerating oral and transdermal formulations. The second generation, from the 1980s to the 2010s, introduced prolonged release using biodegradable polymers for proteins/peptides and early nanoparticles. The third generation, from the 2010s to current, focuses on targeted delivery, non-invasive technology for nucleic acids/peptides, and self-regulating delivery.

How Long-Acting Injectables Stand Out

Oakwood Labs specializes in the development of long-acting injectables for diverse applications, as we believe this method of drug delivery is one of the best options available for medical facilities and patients alike. Some of the key benefits of LAIs include:

• Reduced number of injections required
• Ease of anatomical targeting
• Improved patient compliance
• Reduced possibility of drug abuse
• Variable durations of release, from 1 week to 1 year
• Proven content uniformity
• Easily syringable with 18- to 23-gauge needle

Plus, the Oakwood Labs team is adept at key aspects of the sustained release drug delivery process, including:

• Formulation development
• Scale-up and tech transfer
• GMP aseptic manufacturing

Working with our team means benefitting from our decades of industry experience, and we look forward to partnering with your organization.

Improve Your Operations with LAIs

Contact Oakwood Labs today to learn more about our approach to long-acting injectable development and the expertise we employ throughout the entire process. We look forward to speaking with you and aiding your project.