PLGA Implant Tablet of Ketoprofen: Comparison of in Vitro and in Vivo Releases

Abstract

An implant tablet of ketoprofen (KP) was developed in order to achieve its sustained supply for approximately one week, and its release was evaluated in vitro and in vivo. Implant tablets (30 mg) containing 1 and 5 mg of ketoprofen, prepared using poly(DL-lactic acid-co-glycolic acid) copolymer (PLGA; MW 10000; lactic acid : glycolic acid‫1؍‬ : 1 (mol/mol)) as a matrix, exhibited similar week-long sustained release in vitro. Plasma concentration was monitored after the implant tablet (5 mg of KP) and a KP solution (0.5 mg of KP) were administered subcutaneously to rats, and in vivo release rate was analyzed by deconvolution. The release rate from the implant tablet was faster in vivo than in vitro in the initial phase, but much lower in vivo than in vitro in the later phase. The plasma level decreased to the level less than the minimal effective concentration at 96 h after administration. However, the calculated plasma concentration given by convolution based on in vitro release rate was more than 7 times greater than the minimal effective concentration even at 96 h after administration. As the implant displayed the discrepancy between in vitro and in vivo release rates, the improvement of the in vivo release rate is required.

Development of biodegradable polymeric implants of RGD-modified PEG-PAMAM-DOX conjugates for long-term intratumoral release

“…Based on the measured data and observed phenomena, it can be inferred that the in vivo release of DOX and its conjugates from polymer matrix is faster in speed and shorter in duration than what our in vitro data suggest. As reported previously (Negrin et al, 2004;Takahashi et al, 2004;Onishi et al, 2005), the initial release in vivo might be stimulated by change in implant shape such as mechanical breakdown at the administration site. Besides, the in vivo environment might accelerate biodegradation rate of polymer due to the existence of various biological components involve enzymes.…”

“…With the same formulation and preparation procedure, three implants loaded free DOX and its conjugates showed similar release feature, illustrating that the release kinetics were a function of the polymer matrix rather than the chemotherapeutic agents. Unlike other compressed implantable tablets with burst release (Onishi et al, 2005;Santovena et al, 2009), our study fabricated the implants by a solvent evaporation method, successfully avoid occurring of burst release. The release curves were divided into three phases with different release rates.…”

Preparation and pre-clinical characterization of sustainedrelease ketoprofen implants for the management of pain and inflammation in osteoarthritis

“…However, the IKT3 implant provided relatively quick onset of action with prolonged duration due to its better swelling as well as the prolonged drug release. Results from various studies indicate effective and prolonged drug delivery from polymeric implants in orthopaedics [22][23][24][25].…”

Transdermal delivery of tadalafil using a novel formulation

“…Blood samples (0.5 mL) were collected from the orbital vein before drug administration (0 h) and at the end of 1, 2, 4, 8, 12, and 24 h following percutaneous application of tadalafil gel. Tadalafil was extracted from the rat plasma sample using a modification of the procedure (Onishi et al, 2005). One hundred mL of the plasma sample was placed into a 15 mL centrifuge tube, and 100 mL of 1 N HCl was added.…”