Polymer-based dosage forms

Polymer-based dosage forms continuously administer the drug to the patient for an extended period, which can vary from weeks to years. Various routes of administration are used which include parenteral, transdermal, and intravaginal. The long duration of action, the avoidance of first pass metabolism, and the constant systemic drug concentration levels make these controlled release products very suitable for certain indications, patient populations and drugs. Controlled release contraceptive drugs are an established example which illustrates the benefits. Efficacy of contraceptives is highly connected with compliance and hence conceptive implants serve both efficacy and convenience. In principle the same benefits will apply to other drugs for long-term and chronic indications. Next to better efficacy because of better compliance, avoiding the peaks and troughs associate with taking oral medication can help to reduce adverse side effects.

The function of the polymer in the formulation is to provide the right mechanical properties, maintain the mechanical integrity and to regulate release. In principle various biocompatible polymers can be used either non-degradable or biodegradable. Furthermore, various release mechanisms can be anticipated for example permeation through dense polymers (non-porous) by a dissolution-diffusion mechanism or through mechanisms relying on micro-porosity or pore formation. The choice of polymers is associated with a complex decision matrix which depends on various inputs like the anticipated application, the use duration, drug properties, patient population and so forth.

Commonly used non-degradable biocompatible polymers are polyethylene vinyl acetate (EVA), silicones elastomers and thermoplastic polyurethanes. EVA copolymers can be obtained in grades differing in vinyl acetate content and molecular weight, properties affecting drug release and processability.  More recently, thermoplastic polyurethanes gained increased application. Polyurethane chemistry is very versatile and hence these polymers may have very different properties for example from hydrophobic grades to hydrogels displaying an equilibrium water uptake of more than 100%. Hydrophilic polyurethanes are in principle suitable for the release of hydrophilic drugs and hence are complementary to EVA and silicone polymers which are less suitable for this purpose.

Biodegradable polymers also referred to as bioresorbable polymers is a term that applies to natural and synthetic polymers that degrade in-vivo over time. A common mechanism of degradation is hydrolysis however, enzymatic degradation may play a role as well for certain polymers.  The mechanism of degradation is potentially complex as surface erosion and bulk degradation may take place simultaneously. Furthermore, degradation may be accelerated by autocatalysis because of lactic acid accumulating in the interior of the degrading dosage form. The topic is extensive and cannot be elaborated in detail here, however our polymer experts are available to our customers for guidance and advice.

Several types of dosage forms have been developed for example sub-dermal implants, transdermal patches, vaginal rings, and many other very specific dosage forms. Next to presentation form, controlled release products differ in how drug release is controlled. The simplest concept is a matrix, which is essentially a drug either dissolved or dispersed homogeneously through a polymer and drug release is controlled by permeation through the polymer. Such a matrix can take the form of a ring, implant or other dosage form and it typically displays first order release kinetics. In other words, these systems will display an attenuated release profile with a high on-set release, in the early phase steeply declining in time and never reaching a true steady state. For some applications this is good enough and in case a more constant release is deemed necessary a reservoir system or membrane covered matrix can prove to be a good solution. In this case, the drug loaded compartment is covered by a rate limiting membrane, which result in nearly time independent release profiles. As said co-extrusion is a very suitable technique to produce matrix and reservoir systems as well as further improved concepts.

Our polymer and extrusion experts are eager to collaborate with you on the development of polymer-based delivery systems and in all what we do we have the end goal in mind which is the development of a scalable concept that can be produced robustly against affordable costs at any scale.

Matrix design

Reservoir design

Multilayer design