A correlative model to predict in vivo AUC for nanosystem drug delivery with release rate-limited absorption

Purpose. Drug release from nanosystems at the sites of either absorption or effect biophase is a major determinant of its biological action. Thus, in vitro drug release is of paramount importance in gaining insight for the systems performance in vivo. Methods. A novel in vitro in vivo correlation, IVIVC, model denoted as double reciprocal area method was presented and applied to 19 drugs from 55 nano formulations with total 336 data, gathered from literature. Results. The proposed model correlated the in vitro with in vivo parameters with overall error of 12.4 ± 3.9%. Also the trained version of the model predicted the test formulations with overall error of 15.8 ± 3.7% indicating the suitability of the approach. A theoretical justification was provided for the model considering the unified classical release laws. Conclusion. The model does not necessitate bolus intravenous drug data and seems to be suitable for IVIVC of drugs with release rate-limited absorption

Development and Characterization of Solid Dispersion for Dissolution Improvement of Furosemide by Cogrinding Method

Purpose: The purpose of this study was to prepare and characterize solid dispersion formulation of furosemide to enhance dissolution rate. Methods: Solid dispersions with different drug: carrier ratios were prepared by cogrinding method using crospovidone and microcrystalline cellulose as carrier. The physical state and interactions between the drug and carrier were characterized by Fourier transform infrared spectroscopic (FT-IR) and X ray diffraction (XRD). Results: Solid dispersions (especially with drug: Carrier ratio of 1:2) showed a higher dissolution rate than their respective physical mixture and pure furosemide. Dissolution rate in pH 5.8 was also higher than pH 1.2. The XRD analysis showed that crystalline form was changed to the amorphous state in the solid dispersions. FT-IR analysis did not show any physicochemical interactions in the solid dispersion formulations. Release kinetic of formulations were fitted best to the Weibull and Wagner log probability (linear kinetic) as well as suggested 2 and Gompertz (non-linear kinetic) models. Conclusion: The dissolution properties of furosemide were improved with the use of hydrophilic carriers in solid dispersions due to change in the crystalline form of the drug and more intimate contact between drug and carriers which was dependent on the type and ratio of carrier as well as dissolution medium pH

Design and Evaluation of Delayed-Release Osmotic Capsule of Acetaminophen: Delayed-release osmotic capsule of acetaminophen

Hard gelatin capsule filled with acetaminophen, osmotic agent (sorbitol), a release promoter (sodium dodecyl sulfate), coated with a semipermeable cellulose acetate membrane containing a hydrophobic plasticizer (castor oil) and sealed with white bees wax plug was designed. When placed in the sink water penetrates the membrane, dissolves the osmotic agent and increases the osmotic pressure inside the capsule. The increased osmotic pressure enhances the water imbibition and consequently increases the hydrostatic pressure inside the capsule and when the latter pressure is high enough it expels out the plug and the drug release commences. With cellulose 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), were thickness of semipermeable membrane (0.033-0.112 mm) and plug thickness (2.40-3.40 mm) although the influence of semipermeable membrane thickness was more important than plug thickness in delaying the onset of release. As the statistical analysis revealed, castor oil concentrations in the range of 3-4% (w/w) did not affect the lag time. With the control of the membrane thickness, the onset of release could be adjusted from 2 to 7 h. The formulations with tL of 3.9 and 5.8 h may have practical benefits in that if such systems are administered simultaneously with conventional forms the 6 and 4 times daily drug dosage frequency would be reduced to 3 and 2 times regimens, respectively. A theoretical justification was provided for the observed nonlinear relationship between the onset and/or tL of drug release and thickness of the semipermeable membrane. After the lag time, the drug release fromthe systems conformed to the USP requirements