The study of influence of Carbopol 71G in osmotically controlled push-pull acetaminophen system on the drug release profile and the lag-time

Research in the area controlled release drug delivery systems has been focused on more challenging modalities to deliver a drug at a predetermined rate/and or to a location according to the needs of the body and disease states for a definite time period. The osmotic modality is one of the ways to achieve this. In such a system and particularly in the push-pull osmotic drug delivery system a major challenge is to reduce the lag time. This is the time taken by water to enter into the system and hydrate the polymeric push layer to push it to force the drug in a suspended state in the drug layer out of an orifice. Yielding the drug release. One of the ways is to reduce the time for activation of the push-pull system by reduction of hydration time of the polymers that are used in the system for its solubility and swelling properties.;This research deals with development of an osmotically controlled push-pull acetaminophen system containing CarbopolRTM 71G, Polyox RTM N80, PolyoxRTM 301 and MethocelRTM K100M CR (HPMC) as polymeric agents having varying hydrophilicity and hydration time. Depending on the properties of the polymers, varying amounts of them were incorporated into drug and osmotic layers of the tablets in different proportions to evaluate their influence on the release kinetics of acetaminophen as a model insoluble drug to be released in a suspended state. Cellulose acetate was used as a semipermeable membrane (film-forming) material with polyethylene glycol 600 as a plasticizer cum pore forming agent. The polymer or acetaminophen compacts (layers) were compressed using the Carver press. The polymer layer was color coded for identification. A 10,000-tablet batch of microcrystalline cellulose placebo tablets were directly compressed using the Stokes B-2 Tablet press. Placebo tablets together with color-coded acetaminophen osmotic bi-layer tablets were coated with cellulose acetate in Aeromatic Strea-1 fluidized-bed coating apparatus.;The bi-layered tablet containing hydroxypropyl methylcellulose in the drug layer separated into two layers i.e. the drug layer and the push layer, due to poor bonding/adhesion between the layers, during the fluidized-bed coating process. Inclusion of CarbopolRTM 71G and Polyox RTM N80 in the drug layer resulted into successful bonding between the layers upon compression. The push layer was selected on the basis of fairly fast swelling ability as ascertained from the water uptake study.;Acetaminophen dissolution results demonstrated that the drug release rate was modulated by the altering the ratios of CarbopolRTM71G to PolyoxRTM N80. As the ratio increased, the acetaminophen release rate shifted from the first order to zero order kinetics. This is supported by swelling study data where the higher CarbopolRTM 71G to PolyoxRTM N80 ratio yielded linear water uptake. This ratio corresponds to the zero order acetaminophen release kinetics. Upon increasing the ratio of CarbopolRTM 71G to PolyoxRTM N80 lag time increased from 10 to 10.1 to 12.5 minutes. For all ratios with an initial drug release within 5 minutes, they showed a faster hydration of polymers (CarbopolRTM 71G and PolyoxRTM N80 and) in the push layer. This creates the drug dispersion while faster hydration of PolyoxRTM 301drug layer creates the pressure on the drug layer to disperse the suspension. As expected acetaminophen release rate increased with an increase in the orifice size from 0.5 to 1.0 to 1.6 mm in diameter.;It is concluded that the lag time period and drug release rate kinetics can be affected by the hydration time of the polymers used.