Contract Manufacturing of Molded Dosage Forms and Combination Products
ProMed Pharma is a leading contract manufacturer of polymer-based drug releasing molded dosage forms and combination device components. Working with both established and early-stage medical device and pharmaceutical companies, ProMed develops robust manufacturing processes and platforms for extended drug release from a variety of materials, including silicones and thermoplastics.
Activities within ProMed Pharma are focused on manufacturing processes based on molding silicones or thermoplastics. While work has historically focused on molding silicone drug delivery devices using injection and compression molding techniques, new applications involving degradable and nondegradable plastics are emerging.
Several factors must be considered in optimizing the material formulation and developing a robust molding process. The material system (e.g. liquid silicone vs. high consistency rubber), mixing or compounding technique, API particulate size cure temperature, and molding pressure will all potentially affect the drug release consistency and drug content uniformity of a manufacturing lot. In some cases, lamination or over molding of a thin, drug-free layer can be used to enable more uniform release of drug from the implant.
APIs and Materials of Interest
Implantable drug delivery devices offer several advantages over conventional oral or parenteral dosage forms. First, implantable medical devices allow site specific drug administration where the drug is most needed and may also allow for significantly lower doses of drug which can minimize potential side effects. Second, implantable medical devices allow for sustained release of a therapeutic agent, as highlighted in the accompanying illustration. The last and perhaps most important advantage is patient compliance, as the treatment regimen associated with an implantable medical device is generally less burdensome than pills or injections.
Key materials considerations for materials used in drug delivery include biocompatibility, stability and durability and the ability of the material to control release of the active pharmaceutical ingredient (API). At ProMed, we have extensive experience with a variety of APIs including steroids, sex hormones, microbicides, antibiotics, analgesics, and other small molecule compounds.
Silicones have long been a material of choice for drug delivery given their extreme chemical inertness, range of stable mechanical properties, and ability to compound various APIs within the matrix. Ethylene vinyl acetate (EVA) is also finding use in an increasing number of drug delivery applications. Like silicone, EVA is processed at relatively low temperatures, which helps to minimize risks associated with degradation of the API.
Polyurethanes and acrylate hydrogels have also been utilized in select applications. Partnerships with leading suppliers give us access to world class implantable materials and expertise to ensure the safety and performance of your product. Typical part geometries include molded caps, rings, and cylinders as well as more complicated designs. Another option is to use a biodegradable material such as poly(lactic-co-glycolic acid) or PLGA to controllable release the drug while essentially “dissolving away” by hydrolysis to produce lactic and glycolic acid.
Implantable medical devices are called upon to serve a variety of functions, from vascular stents that preserve blood flow to electrostimulation devices that regulate heart rhythm or block spurious signals in the brain, to orthopedic devices that mechanically reinforce the spine or restore range of motion of hips and knees. For over a decade there has been an increasing convergence between implantable devices and drug therapies, leading to combination devices that deliver drugs as either a primary or secondary mode of action. Key markets for ProMed’s contract manufacturing services include cardiovascular, neurology, and orthopedics. Representative drug-device applications include steroid-eluting pacing and defibrillation leads, drug balloons, implantable sensors, antimicrobial catheters, and wound or joint spacers.
Molded and Extruded Pharmaceutical Dosage Forms
Subcutaneous solid implants provide long-term, “passive” release without the need for replenishment. Typically found as thin flexible rods or “matchsticks”, these delivery systems are particularly effective for the delivery of highly potent drugs such as hormones. Additional indications in development include subcutaneous implants for treatment of schizophrenia, breast cancer, photosensitivity, and Parkinson’s disease.
A number of promising solid implant applications can also be found in ophthalmology for the treatment of back of the eye diseases using steroid, with products in development for the treatment of glaucoma (prostaglandins) and age-related macular degeneration (anti-VEGF).
Other novel drug delivery forms such as intrauterine devices (IUDs) and intravaginal rings (IVRs) and are finding increasing applications in the area of women’s health. ProMed is working with leading companies and research groups in this area on IVRs for contraception, hormone replacement therapy, and HIV. Emerging applications in fertility, oncology, and treatment of fibroids are also being explored. In particular, ProMed has demonstrated core-sheath and multi-segment IVR design capable of delivering multiple APIs over a wide range of drug loads and release rates.
ProMed utilizes both in-house testing and partnerships with state-of-the-art analytical facilities to ensure that drug content, drug elution, purity, mechanical strength, and dimensional specifications are consistently met. ProMed Pharma’s Quality Assurance is dedicated to delivering drug eluting components of the highest quality that can be used in implantable pharmaceutical products and/or life sustaining medical devices.
Our Quality System was designed using the 21 CFR 820 Quality System Model and supplemented with applicable sections of 21 CFR 210 & 211 GMPs. ProMed Pharma has also elected to be compliant with ISO13485 standards.
Let’s discuss your potential project and see how the ProMed Pharma team can assist with the successful launch or on-going production