Design and Evaluation of Delayed-Release Osmotic Capsule of Acetaminophen

Hard gelatin capsule filled with acetaminophen, osmotic agent (sorbitol), arelease promoter (sodium dodecyl sulfate), coated with a semipermeable celluloseacetate membrane containing a hydrophobic plasticizer (castor oil) and sealed withwhite bees wax plug was designed. when placed in the sink water penetrates themembrane, dissolves the osmotic agent and increases the osmotic pressure insidethe capsule. the increased osmotic pressure enhances the water imbibition andconsequently increases the hydrostatic pressure inside the capsule and when the latterpressure is high enough it expels out the plug and the drug release commences. withcellulose acetate concentration constant in membrane forming solution, 11% (w/w),the factors affecting the onset of the drug release, i.e. the lag time (tl), werethickness of semipermeable membrane (0.033-0.112 mm) and plug thickness (2.40-3.40 mm) although the influence of semipermeable membrane thickness was moreimportant than plug thickness in delaying the onset of release. as the statisticalanalysis revealed, castor oil concentrations in the range of 3-4% (w/w) did not affectthe lag time. with the control of the membrane thickness, the onset of releasecould be adjusted from 2 to 7 h. the formulations with tl of 3.9 and 5.8 h may havepractical benefits in that if such systems are administered simultaneously withconventional forms the 6 and 4 times daily drug dosage frequency would be reducedto 3 and 2 times regimens, respectively. atheoretical justification was provided forthe observed nonlinear relationship between the onset and/or tl of drug release andthickness of the semipermeable membrane. after the lag time, the drug release fromthe systems conformed to the usp requirements.