Dr Steffen Denzinger and Dr Adela Kalivoda of global pharmaceutical company Merck Millipore discuss the benefits of using hydrogels incorporating polyvinyl alcohol in controlled-release applications such as patches, creams and even parenterals.
Controlled release has become a central topic in the development of pharmaceutical formulations over the past decade. It allows making best use of the efficiency of an active compound by delivering the right amount at the right time to the blood stream.
Hydrogels are an attractive matrix for controlled-release systems to be used in patches, creams, ointments and even in parenterals. Even though a matrix based on a hydrogel is semi-solid or even of a colloidal structure in the interior, it shows the same potential as a solid matrix in respect to release patterns. Depending on the hydrophilicity, the degree of crosslinking and the swelling behaviour of a basic polymer, hydrogels can be tailored according to the needs of the formulator. Numerous hydrophilic polymers have been described for use in hydrogels, starting with polyacrylates and methacrylates, polyethylene glycol, polylactic acid (PLA), poly(lactic-co-glycolic acid) (PLGA), poly(N-isopropylacrylamide) (poly-NIPAM) and polyvinyl alcohol (PVA).
Chemically, the choice of a polymer for hydrogel formation is extremely wide. The desired characteristics of a hydrogel for an application in the pharmaceutical and medical sector are, among others, sterility, harmlessness and efficient water absorption. Additionally, the formulator needs to ensure compliance to pharmacopeias as well as to global regulation. So the problem for the formulation is to obtain highly functional materials, which are produced by the highest possible quality standards. PVA meets all these demands, coupled with the additional benefits of multiple available manufacturing methods and a simple chemical structure that can be easily modified to fit one's needs and transparency.
Merck Millipore offers a range of compendial PVAs that are suitable for designing controlled-release hydrogels. By irridation, basic PVA can be crosslinked so that the formulator can easily control the release pattern, i.e. the degree of sustaining the release, as long as he has a clearly defined matrix to start with. The Merck Millipore PVA product range offers exactly this. Compendial-grade PVA is available in several molecular weights with a clearly defined distribution without tailing into the high molecular weight area, which can lead to problems due to the lower solubility of polymer chains with high molecular weight. Furthermore, there is a very strict specification on crotonaldehyde, which is a toxic by-product of the synthesis route, and even though its content is not specified by any pharmacopeia it is crucial for the application to have reproducibly low levels. This can be realised only by strict control of the manufacturing conditions. In addition, endotoxin and microbiology testing ensure a safe product with a minimised risk from impurities, which is especially important for hydrogels as these are systems on an aqueous basis or for parenteral use.
Applicational examples of typical controlled-release hydrogels utilising PVA include controlled-release patches containing lidocaine, which is available from several manufacturers, and patches containing fentanyl, indomethacin and felbinac or even combinations of active ingredients such as lidocaine and tetracaine. PVA-based hydrogels can be used as well in the aqueous phase of ointments to create sustained-release semi-solid dosage forms. In literature, PVA-based hydrogels have even been described for controlled oral delivery of insulin and for pulsed delivery of heparin. Enhancing bioavailability of drug products by solutions ensuring the delivery of the right amount of active at the right time does not always require complicated systems.
In addition to the widespread possibilities for using the highly defined Merck Millipore PVAs in any controlled-release hydrogel application there is the additional benefit for the formulator that all Merck Millipore PVA grades are part of the Emprove range, which means there is a comprehensive regulatory package around the product helping to ensure that time-to-market is as fast as possible.