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A New Bioerodible Polymer Insert for the Controlled Release of Metronidazole (1994)

Gates, Kimberly A. ; Grad, Helen ; Birek, Peter ; [et al.]

Springer

Pharmaceutical research 11 (1994), S. 1605-1609

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ISSN: 1573-904X

Keywords: bioerodible association polymer ; metronidazole ; cellulose acetate phthalate (CAP) ; Pluronic L101 ; periodontal pocket insert ; controlled drug delivery

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology

Notes: Abstract This study evaluates a new class of bioerodible polymers as periodontal inserts for the controlled release of metronidazole. The system is based on association polymers formed from compatible blends of cellulose acetate phthalate (CAP) and a hydrophobic block copolymer of polyoxyethylene and polyoxypropylene, Pluronic L101. In addition to characterizing these polymers by thermal analysis, their erosion and metronidazole release characteristics were determined both in vitro, and in vivo using a rat model. The results show that increasing the concentration of Pluronic L101 in the blend to 50% and above leads to a sharp reduction in the rates of polymer erosion and metronidazole release. The characteristics of these slowly eroding films are potentially suitable for use as periodontal drug inserts with an effective duration of up to several days. Depending on the blend composition, the mechanism of metronidazole release was found to range from a surface erosion-controlled process to an erosion-modulated diffusion process. In all in vivo experiments, no signs of adverse tissue reactions were detected. Based on these results, prototype delivery inserts were designed and subsequently evaluated in volunteer patients. Preliminary results from this pilot study show that the metronidazole concentration in the gingival crevicular fluid was significant throughout the sampling period of up to 3 hr and remained well above the minimum inhibitory concentration for most periodontal pathogens. In addition, no discomfort or irritation was reported by the test subjects.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1018913921956

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Plasticizer permeation across mucosal tissue: An experimental and theoretical study (1991)

Pink, David A. ; Foong, Wai-Choong ; Jones, Derek W. ; [et al.]

New York, NY [u.a.] : Wiley-Blackwell

Journal of Applied Biomaterials 2 (1991), S. 41-48

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ISSN: 1045-4861

Keywords: Chemistry ; Polymer and Materials Science

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Medicine , Technology

Notes: In vitro transmucosal permeation of (14C)-dibutyl phthalate [(14C)DBP], across intact mucosal hamster tissue compared to keratin-stripped mucosal tissue indicated no significant difference (p ≈ 0.069) in (14C)-DBP. However, significantly greater (p 〈 0.022) DBP was found to be concentrated in the keratin-stripped after a period of 6 h. The amount of (14C)-DBP permeating both tissues followed a similar linear increase for next 3 h. However, between 3 and 4 h, the rate of permeation through the untraumatized tissue significantly decreased. This was followed by a rapid linear increase for the next 3 h. In contrast, the cumulative amount of (14C)-DBP permeating the traumatized tissue showed a linear correlation (r = 0.995) over the 6-h period. A theoretical two-layer model was constructed to allow computer simulations of the (14C)-DBP permeation. It was indicated that an average diffusion coefficient for a single DBP molecule through the intact keratin layer would be ∼ 100 times less than through the remaining layer of the model. The model has enabled a possible explanation to be put forward, describing the role of the keratin layer in the permeation of plasticizer mucosal tissue.

Additional Material: 4 Ill.