A biopharmaceutic approach in designing a controlled release tablet of sodium monofluorophosphate: 1. In vitro and in vivo studies in beagle dogs.
The purpose of this study was to develop a controlled release tablet (CRT) of sodium monofluorophosphate (NaMFP) based on biopharmaceutic and pharmacokinetic principles. NaMFP was introduced in the early eighties to treat osteoporosis. The required dose size (200 mg of NaMFP) and time of drug delivery (8.3 h) were theoretically determined based on the pharmacokinetic parameters of fluoride (F-). A CRT was formulated with ethyl cellulose (EC) by the direct compression method. The ratio of drug to polymer was adjusted 1:1, after studying the in vitro release profiles. The release mechanism from the developed dosage form followed the square root of time relationship. This dosage form was evaluated for its in vivo performance in dogs. The pharmacokinetics of F-, after the IV and PO administration of NaMFP, was determined to standardize the animal model. F- followed a two-compartment model and no significant differences were found between the two routes of administration. The bioavailability in dogs was only 60%. The reason for this poor bioavailability was postulated to be the delivery of drug extended beyond the principal sites of absorption of the gastrointestinal tract. Hence, we decided to characterize the absorption sites of NaMFP and to modify the CRT.
Vattikonda
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Division of Pharmaceutics and Drug Delivery Systems, University of Cincinnati Medical Center, OH 45267-0004.
Ritschel
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WA
D000704:Analysis of Variance; D000818:Animals; D001682:Biological Availability; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004285:Dogs; D004333:Drug Administration Routes; D005459:Fluorides / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D007408:Intestinal Absorption; D016014:Linear Models; D008297:Male; D010024:Osteoporosis / Q000188:drug therapy; D010710:Phosphates / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010865:Pilot Projects; D013607:Tablets
D003692:Delayed-Action Preparations; D010710:Phosphates; D013607:Tablets; C012980:fluorophosphate; D005459:Fluorides