Local ofloxacin delivery using a controlled‐release insert (PT‐01) in the human periodontal pocket

Abstract

PT-01, a controlled-release insert, was developed for topical chemotherapy in periodontal disease. It is a soluble insert that consists of fast-release and sustained-release parts containing ofloxacin (OFLX) as an antibacterial agent. In this study, the release profile of OFLX from PT-01 was investigated in vitro. Twelve adult volunteers were administered OFLX as PT-01 or as an aqueous solution into their periodontal pockets, OFLX concentrations in gingival crevicular fluid (GCF) were evaluated from the viewpoint of pharmacokinetics. The in vitro release profile of OFLX from PT-01 showed a biphasic pattern. The release rate of OFLX was relatively rapid in the early phase and slow thereafter. When OFLX aqueous solution was administered into periodontal pockets, the OFLX level in GCF rapidly decreased to be about 1/100 after 30 minutes. When PT-01 was inserted into the pockets, the OFLX level in GCF immediately reached a peak (about 12 mg/ml), and gradually decreased until the 3rd day, and maintained a constant level above 2 micrograms/ml, the effective minimum antibacterial concentration for periodontopathic microorganisms, from the 3rd to 7th day after insertion. No side-effects were observed in the volunteers who received the PT-01 insert. The above results suggest that PT-01 is a suitable pharmaceutical preparation for periodontal chemotherapy.

Subgingival Delivery of Therapeutic Agents in the Treatment of Periodontal Diseases

“…The use of this formulation has also been shown to provide significantly better results than routine therapy in the maintenance of periodontal pockets over a two-year period (Stabholz et al, 1991). A formulation releasing tetracycline over a seven-day period ) also produced significantly better results than scaling and root planing alone over 12 weeks (Noguchi et al, 1984) and ofloxacin (Higashi et al, 1990;Kimura et al, 1991) have been tested clinically. The first report on a degradable intrapocket sustained-release delivery system was the study by Noguchi et al (1984) using hydoxypropylcellulose films.…”

“…Although this was a pioneering study in the development of a degradable system, the rapid degradation of the device and the short duration of drug exposure were distinct disadvantages. Using a modification of this system by incorporating slowly soluble methacrylic acid copolymer particles into the hydoxypropylcellulose films (Higashi et al, 1990;Kimura et al, 1991), investigators prolonged the release of the drug ofloxacin from the device such that 70% was released in the first 8 hrs in vitro. In vivo levels above 2 pg/mL of ofloxacin were maintained for 7 days after treatment with the device.…”

Ethyl Cellulose and Polyethylene Glycol-Based Sustained-Release Sparfloxacin Chip: An Alternative Therapy for Advanced Periodontitis

“…[38] The results of the antimicrobial activity tests proved that the embedding of sparfloxacin in a polymeric matrix consisting of ethyl cellulose sustains and does not inhibit the biological activity of the drug. This concept was based on the study done by Higashi and Morisaki.…”

Comparative evaluation of locally delivered minocycline and metronidazole in the treatment of periodontitis

“…[14] Since then, chlorhexidine (Addy 1982),[15] doxycycline (Garret 1999),[8] minocycline (Jones 1994),[5] metronidazole (Addy 1982)[15] and ofloxacin (Higashi 1990)[16] antimicrobials in the formulation of local delivery devices, have been used for the treatment of periodontitis with variable results.…”