In vitro and in vivo evaluation of in situ forming polyester implants for the extended release of carvedilol.

ABSTRACT

Polyester based in situ forming implants (ISFIs) are injectable long-acting drug delivery systems that offer a wide range of unique advantages. As a result of these advantages, two relatively high molecular weight, ester terminated grades of poly (D,L-lactide-co-glycolide) (PLGA) and poly(D,L-lactide) (PLA) were evaluated for their ability (i) to form ISFIs loaded with carvedilol, and (ii) to control its release both in vitro and in vivo. At a polymeric concentration of 40% w/w, implant solutions were syringeable, injectable, and able to encapsulate carvedilol to a high degree (encapsulated drug% > 97%). When visualized using scanning electron microscopy (SEM), implants were found to have a dense thin surface atop porous sublayers. As for their in vitro evaluation, PLGA and PLA implants were able to maintain drug release over the course of 49 and 84 days, respectively. On the other hand, in vivo drug release from both implants was almost identical and lasted for only 42 days. This may be due to the overriding effect of the similar host environment at the injection site that diminished the effect of polymeric physiochemistry on phase inversion and drug release. Lastly, while the polymer-free drug/NMP solution completely released its drug content within the initial half hour in vitro, the formulation extended drug release in vivo. This could be due to a yet to be investigated interaction between carvedilol and NMP under in vivo conditions. These results cement the significance of formulating carvedilol loaded ISFIs for the management of chronic conditions.