Nov 21 2012
Table of Contents
Introduction
Applications
State-of-the-art
Materials
Controlled Release Systems
Mechanisms of Release
Patented Controlled Release Technologies
Challenges
Future
Conclusion
About Ceram
Introduction
Modern biomedical applications and drug delivery have paved the way for controlled release technologies in the healthcare industry. This paper details the nuances of controlled release systems, studies the mechanisms of release currently used and examines the materials this technology employs. This study describes the advantages of materials such as polymer, glass, and ceramic, with special emphasis the application of these and hybrid ceramic components to meet the current challenges linked with controlled release technologies.
As a concept, controlled release differs from instant release. Controlled release is associated with slowly releasing an agent so that its concentration or availability is maintained over a period of time. Controlled release can be distinguished as: slow or sustained controlled release, or triggered release. The former involves controlling of the availability through the delivery of an agent for an extended time period. The latter refers to tailoring the delivery to meet the requirement of environmental stimuli that permits the selection time, site and conditions of delivery.
Prolonged delivery of active ingredients offers advantages such as efficient action of the agent, elimination of side effects, reduction in dosage frequency, and separation of incompatible or unstable compounds. Figure 1 illustrates the benefits of controlled release versus instant release.
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Figure 1. Controlled release vs. instant release
Applications
Though controlled release is largely associated with drug delivery and widely used in biomedical applications, the scope of the sustained release technology includes applications in a variety of sectors such as agriculture, pesticides, paint coatings, marine industry, personal care and cosmetics. Table 2 presents an overview of the applications areas of this technology.
Table 2. Examples of Areas of Applications of Controlled Release
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Area of application |
Examples |
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Paints |
Hybrid sol–gel derived films for environmentally-friendly corrosion protection of metals
Encapsulated biocides in silica networks added to coatings for controlled delivery to reduce the amount of biocide released to the environment and maintain a minimum concentration at the coating interface, over time |
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Agriculture |
Nutrients, herbicides, fungicides, pesticides
Controlled release formulations for reducing leaching of herbicides and contamination of groundwater. Use of natural or environmentally compatible materials as carriers (of special interest in terms of economy and sustainability)
Controlled release formulations for decreasing pesticide mobility through the soil and protect from photodegradation.
Polymer-coated controlled release fertilizer as green fertilizer for controlling contamination in agriculture
Glasses that release slowly trace elements used as fertilizers Copper and trace element glass boluses for the slow release of nutrients as dietary supplements in animal husbandry |
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Pharmaceuticals |
Ceramics, glasses and glass-ceramics for the delivery of drugs, peptides, hormones, anti-inflammatory agents, antibiotics, vitamins, etc
Bioactive and resorbable bioceramics, glasses and glassceramics for coatings of implants for dental applications and bone regeneration. Used as fillers for restorative materials or as scaffolds
Controlled release of local anaesthetics and antiseptics in tissuecompatible wound dressings |
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Household and personal care |
Nanocapsules for loading and release of antimicrobial molecules used as additives in household surface cleaning
Polyurethane hollow microcapsules sprayed on leather and textiles that release perfume when subjected to pressure Controlled release of insecticide microcapsules for common household insect pest control
Extended release over time of fragrances for air freshener products
Active bioglasses in toothpaste formulations and tooth whitening products |
|
Cosmetics |
Controlled release of retinol in anti-ageing products from silica particles
Soluble glasses as anti-ageing ingredients by releasing ions in an aqueous medium |
|
Food |
Controlled release of flavours for greater intensity and for long periods of time
Thermally sensitive controlled release of flavour compounds to improve the appeal of frozen baked foods upon heating Active packaging materials able to release antimicrobial compounds into foodstuffs to inhibit or slow down bacterial growth during storage |
State-of-the-art
The active agent’s physical and chemical properties, route of delivery and application are the driving factors of choosing the type of controlled release system and the delivery mechanism. The compatibility with active ingredients plays a major role in the selection of materials.
Material
Recently developed materials can be classified into two major groups: Polymers and Glass and Ceramics.
Polymers
Controlled release applications widely use biodegradable and non-biodegradable polymers. In recent years, despite the success of polymeric systems, a distinct need for alternatives has emerged in controlled release applications.
Glass and Ceramics
Ceramic and glass materials have proven to be excellent carriers for sustained release. To produce ceramic and glass materials for controlled release applications, the fusion and sol-gel routes can be applied. Figure 2: illustrates the active agent’s release profile in sol-gel glass carriers of identical composition, but dissimilar physical properties and morphologies.
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Figure 2. Release profile of an active agent in sol-gel glass carriers with the same composition but different physical properties and morphologies related to the synthesis parameters
Controlled Release Systems
Reservoir Systems
A common method to obtain reservoir-type carriers for controlled release is microencapsulation. Fig 3 illustrates the synthesis of silica microcapsules through sol-gel for an over-the counter drug.
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Figure 3. Silica microcapsules synthesized via sol-gel as controlled released carriers for an over-the counter drug
Matrix Systems
Here the agents are homogeneously dissolved or dispersed throughout the material processed to the required shape and geometry. The release rate is affected by the type of material, its geometry and concentration of the active agent. Figures 4 and 5 present examples of porous and non-porous silica carriers
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Figure 4 and 5. Examples of porous and non-porous silica carriers including a dispersed over-the-counter drug
Mechanisms of Release
Diffusion Controlled Release
A matrix that consists of a degradable or non-degradable material confines the agent. The release mechanism involves the migration and diffusion inside the reservoir to the matrix surface subsequently the supply of the active compound in the interface between the surrounding medium and the matrix, and end with the delivery into the medium from the surface.
Solvent-Activated Release
Some materials, affected by altered interactions and changes in hydrophobicity between the organic groups, demonstrate reversible swelling/shrinkage in water. This behavior improves the movement of the structural chains supporting the agent molecules’ diffusion and release.
Osmotically-controlled Release
Osmotic systems are promising when it comes to the delivery of poorly soluble compounds. Osmotic pressure facilitates the ejection of the active ingredient dispersed in a polymeric matrix and which cannot diffuse through it. Figure 6 illustrates the osmotic pressure created by allowing the fluid to flow into its dosage form.
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Figure 6. The osmotic pressure is created by the flow of fluid into the dosage form. The rate of release of the drug from the dosage form is directly proportional to the osmotic pressure
Stimulus-responsive Release
Materials that are smart and capable of adapting their response to environmental parameter changes show promise for controlled release.
Chemically-activated Release
In biodegradable polymers, drug release takes place when non-soluble polymers hydrolyzes into tinier non toxic molecules.
Patented Controlled Release Technologies
There are multiple controlled release technologies in oral, transdermal, injectable and implantable forms are available in the market. This table below lists some patented controlled release osmotic systems.
Table 1. Patented Controlled Release Technologies
|
Technology |
Route |
Description |
|
Port® |
Oral |
Two dosage formats: tablet or capsule. A polymeric matrix containing the drug is coated by a semi permeable polymer rate-controlling polymer. An initial dosage is released followed by the release of a second dosage of the agents contained in a gelatine core coated with a semi permeable membrane. When placed in contact with an aqueous medium, the water diffuses and increases the osmotic pressure and therefore ejects the agent after a lag time dependingon the coating thickness. |
|
Flamel |
Oral |
Capsules or tablets containing microparticles which are liberated in the stomach and pass into the small intestine, where each microparticle delivers the drug. Effective control of release of multiple drugs and for delayed/extended delivery of small molecules with a narrow window of absorption. |
|
Oros® |
Oral |
A semi permeable membrane surrounds a tablet core consisting of a drug layer containing a poorly soluble drug that is enclosed by a sacrificial push layer containing a water swellable polymer as osmotic agent. Upon contact with an aqueous medium, the osmotic agent facilitates the ejection of the confined drug. |
|
EnSotrol™ |
Oral |
Delivery is caused by water entering the core of a reservoir through a membrane where there is a solubility enhancer that helps to dissolve the compound. The solution containing the active agent of interest is then delivered through the exit orifice. |
|
Duros™ |
Injectable |
Through osmosis, water from the body is slowly drawn through a semi-permeable membrane. An osmotic agent expands and displaces a piston-like structure to dispense small amounts of drug formulation from the drug reservoir through the orifice. |
|
DermaSal™ |
Transdermal |
Patch consisting of a rate-controlling polymeric matrix. |
|
MicroSal™ |
Oral/implants |
Hydrophobic microspheres in the form of a free-flowing powder. They provide high retention of ingredients and can be utilized for sustained release, targeted delivery, and heat triggered release. It can be incorporated in both aqueous and anhydrous products in applications such as healthcare, household, personal care and food. |
|
Lipoparticle™ |
Topical |
Microencapsulation of an active agent. Either in a capsule of a shell material surrounding a single droplet or particle of a hydrophobic core material or consisting of many small droplets of material entrapped in a polymer matrix. Suitable for the incorporation of both hydrophobic and hydrophilic materials. |
Challenges
Key drivers for further advancements in the field of controlled release include reduced processing and production costs, improved efficiency and beneficial effects. In specific therapies such as the administration of antiretroviral drugs for HIV/AIDS treatment, controlled release technologies have overcome drug solubility issues and to enhance the targeting of the designated sites. In the recent years, materials, glasses and ceramics have gained increasing attention.
Future
Glasses and ceramics, due to their intrinsic bioactivity, exhibit a dual function, adding value as an inert matrix in certain biomedical and pharmaceutical applications. Employing hybrid materials with up to 80% high ceramic component to avoid the inconsistency of properties of polymeric systems has presented best results. Bioactive glass - polysulfone composites and sol-gel glasses or ceramics combined with gelatine or, polylactic acid or dextran composite scaffolds are some of the examples for hybrid materials.
Conclusion
Hybrid materials made of a variety of glasses and ceramics exhibit better characteristics with respect to their elements, in terms of improved biocompatibility and a slower active compound release. Glasses and ceramics show promise to handle some of the prevailing challenges and hold potential for controlled release in new fields.
About Ceram
Ceram is an independent global expert in materials testing, analysis and consultancy. Ceram provide customized solutions that can help you to measurably improve performance and profitability through safer, regulatory-compliant and better-engineered products.
Ceram experts set new standards in materials testing and work as an extension of our clients’ teams, applying their expertise and capabilities to a wide range of industries, including:
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Aerospace & Defence
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Automotive & Transport
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Construction
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Consumer & Retail
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Electronics
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Energy & Environment
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Healthcare
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Materials Manufacturing
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Minerals
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Refractories
Headquartered in Staffordshire, UK, Ceram has accredited laboratories and offices around the world and employs a team of research and product development professionals who specialize in physical and chemical materials testing, research, process engineering, failure analysis and product design.
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This information has been sourced, reviewed and adapted from materials provided by Ceram.
For more information on this source, please visit Ceram.