Drug release from in situ forming implants and advances in release testing

In situ forming implants, defined as liquid formulations that generate solid or semisolid depots following administration, have shown a range of advantages in drug delivery. This drug delivery strategy allows localized delivery, sustained drug release over periods of days to months, and is a less invasive option compared to traditional solid implants which typically require surgical implantation. Unfortunately, there are a number of quality control challenges in terms of drug release testing of these delivery systems which is likely to have contributed to the relatively few commercially available in situ forming implant products. This article reviews current marketed in situ forming implant products, FDA guidance on in vitro release testing, and formulation and environmental parameters influencing drug release from in situ forming implants. Formulation considerations for development of biological agents loaded in situ forming implants are also discussed. The advantages and limitations of typically used in vitro release testing methods are summarized. Difficulties in the development of in vitro-in vivo correlations (IVIVCs) for in situ forming implant are discussed. The knowledge presented will be helpful for the development of in situ forming implants, as well as for the development of appropriate in vitro testing methods and IVIVCs.