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Objective: The aim of this study was the development and pharmacokinetic/pharmacodynamic evaluation of the in vivo release of subcutaneous implants of carvedilol capable of providing stable tissue levels in experimental models of hypertension. Methods: The subcutaneous implants were prepared with poly (epsilon-caprolactone) (PCL) and different proportions of the SoluPlus (SP) hydrophilic polymer (300:0; 250:50; 150:150 and 50:250 mg) loaded with 100 mg carvedilol. The plasma profile and the effect on systolic blood pressure (SBP) after subcutaneous implantation of each formulation was evaluated in male spontaneously hypertensive rats (SHR). Results: The PCL:SP 50:250 and 150:150 formulations provided levels ranging from 100 to 200 ng/mL and the PCL:SP 250:50 and 300:0 formulations provided lower concentrations of carvedilol ranging from 0 to 100 ng/mL during the treatment period. Spontaneously hypertensive animals treated with the PCL:SP 50:250 y 150:150 implants presented a significant decrease in SBP (PCL:SP 50:250: DPAS: –36.6 ± 2.0 mm Hg; PCL:SP150:150: -35.7 ± 2.2 mmHg; p <0.05 vs. baseline values) Conclusions: The incorporation of the SoluPlus hydrophilic polymer in PC:SP 150:150 and 50:250 implants increases the release of carvedilol, since it provides plasma concentrations ranging from 100 to 200 ng/ml, resulting in a sustained reduction of indirect SBP in SHR.

revista argentina de cardiologia

Desarrollo de implantes subcutáneos de liberación controlada de Carvedilol para la reducción sostenida de la presión arterial en modelos experimentales de hipertensión arterial