Key bioavailability features of a new extended-release formulation of minocycline hydrochloride tablets.

PMID 17436824


For a long time, minocycline has been recognized as highly efficacious for the treatment of acne vulgaris but with use-limiting acute vestibular adverse events (AVAEs). Based on the concept that lowered overall systemic exposure to minocycline should reduce unwanted side effects, a program was initiated to develop a modified-release formulation for clinical testing. An extended-release (ER) minocycline hydrochloride tablet formulation was developed that demonstrated delayed time of maximum concentration (tmax, 3 1/2 - 4 hours) compared with a nonmodified-release minocycline (tmax, 2 1/4 - 3 hours), and a lower maximum concentration of drug (cmax) in the blood (90%) compared with nonmodified-release formulations. At steady state (day 6), the ER-minocycline formulation had a 0- to 24-hour area under the curve (AUC(0-24)) and cmax of 33.32 microg x h/mL and 2.63 microg/mL, respectively, compared with 46.35 micro x h/mL and 2.92 microg/mL, respectively, for the nonmodified-release minocycline. These studies demonstrated that the new ER-minocycline hydrochloride formulation is not bioequivalent to the immediate-release (IR) minocycline hydrochloride formulation currently on the market. The favorable pharmacokinetic profile of ER minocycline also was not affected by concomitantly ingested food, including dairy products.