By Adela Kasselkus, et al
With target-oriented drug discovery and an increasing focus on specialized medicines, the manufacturing of final drug products is becoming more and more complex. The processing and formulation of active pharmaceutical ingredients (APIs) designed with a specific target and functionality in mind may present challenges during the development and manufacture of the final formulation. Aspects such as bioavailability of the API in the body, API stability, and low dosage formulations are frequent hurdles to be overcome when bringing a drug to the
It has been observed that approximately 60% of new chemical entities (NCEs) have solubility issues, compared to 39% of marketed APIs. Sufficient solubility of the API is an important factor for the absorption of the API into the body and thus the API’s therapeutic effect in vivo. Solubility may be increased by using specific solubility enhancing techniques and excipients in pharmaceutical formulation. Controlled release of the API continues to be another area of major interest in the pharmaceutical sector, as it allows the performance of the final formulation to be adapted to the therapeutic need. Sustained release as a specific controlled-release drug delivery model makes it possible to address issues highly relevant to long-term therapy, such as dosing regime, convenience, and patient compliance, as well as the efficacy-to-safety ratio.
While novel solutions, excipients, and innovative technologies can open up new pathways to improved formulations, it is important to note that they may also induce hurdles to regulatory approval. Novel excipients require in-vitro and in-vivo safety assessments, as well as in-depth regulatory review. These additional assessments can result in unplanned costs and delays, and add a further dimension to the risk evaluations of taking the final drug product to market. However, new does not always mean novel. Using familiar materials in innovative ways can result in new solutions that offer the peace of mind and safety of tried and trusted excipients.
One of these familiar excipients, which shows great and not yet fully exploited potential for new formulation approaches, is polyvinyl alcohol (PVA; sometimes also referred to as PVOH in other sources). It is a synthetic polymer produced by the polymerization of vinyl acetate and partial hydrolysis of the resulting esterified polymer.
PVA is currently used very commonly in pharmaceutical products across the different classes of marketed new molecular entities, new formulations and new indications (Fig. 1). While PVA is predominantly applied in oral formulations, typically in tablet coatings, other marketed drug products that utilize the distinct features of the various commercially available PVA grades can also be found in ophthalmic, transdermal, and topical dosage forms, for instance (Fig. 2). This publication will focus on additional applications of PVA for sustained release and solubility enhancement that address the aforementioned challenges in pharmaceutical formulations.