A Prodrug Approach Involving In Situ Depot Formation to Achieve Localized and Sustained Action of Diclofenac After Joint Injection

Prodrugs as empowering tools in drug discovery and development: recent strategic applications of drug delivery solutions to mitigate challenges associated with lead compounds and drug candidates

“…47). 231 Prodrug 5m displayed pH-dependent solubility (6.5 mg mL −1 at pH 4 and 4.5 μg mL −1 at pH 7.4) and was readily converted to 5l in biological matrices, with the rate increasing in the order of rat serum >human plasma >synovial fluid from arthritis patients. Following the addition of a solution of the prodrug to a donor cell containing 80% synovial fluid in a rotating dialysis model that would mimic drug transport in the synovial environment, the continuous appearance of 5l in the acceptor phase was observed for up to 43 h following an initial lag time of 8 h. Following an IA injection of a slightly acidic formulation of 5m into the knee joints of rats, the prodrug persisted for up to 8 days.…”

Localized and targeted delivery of NSAIDs for treatment of inflammation: A review

“…In cases where the vehicle is small enough and has a low enough viscosity to pass through a needle, the introduction of this delivery system to the body is facile (Table 3). [26][27][28][29][30] Typical systems which have these desired properties are nanoparticles or conjugate systems. 26,29,30 While long-term delivery is not required for this type of delivery, it is advantageous as osteoarthritis is the main research focus for this vehicle type.…”

“…26,29,30 While long-term delivery is not required for this type of delivery, it is advantageous as osteoarthritis is the main research focus for this vehicle type. 26,27,30 Injections into affected joints, such as knees, can be done as required, but fewer injections are preferred for higher patient compliance. In this category, there are two papers which show impressively long release profiles and long-term therapeutic efficacy.…”