Microspheres with pH modulated release: design and characterization of formulation variables for colonic delivery.
The aim of this study was to design and develop microspheres of indomethacin with pH and transit time dependent release properties for achieving targeted delivery to the colon. Microspheres containing varying proportions of ethyl cellulose and Eudragit (L100 or S100) either alone or in combination were prepared using an oil-in-oil emulsion-based solvent evaporation technique. System comprising of acetone (internal phase) and liquid paraffin (external phase) in the ratio of 1 : 1 and 1 : 9 yielded microspheres with good physical properties (spherical and discrete), high drug loading (70-80%) and entrapment efficiency (70-85%). The lag time in the initial release depended on the proportion of pH-sensitive polymer Eudragit, while the duration of indomethacin release from microspheres was found to be directly proportional to proportion of the total polymer. Thus, a pH- and time-modulated sigmoidal release pattern could be observed in optimized formulations with less than 10% drug release in 4-6 h followed by controlled release extending up to 14-16 h.
Chandran
Sajeev
S
Formulation Development and Pharmacokinetic Laboratory, Pharmacy Group, Birla Institute of Technology and Sciences, Pilani, Rajasthan, India. sajeev@bits-pilani.ac.in
Sanjay
Kango Surbhi
KS
Ali Asghar
Laila Fatima
LF
D000096:Acetone / Q000737:chemistry; D000180:Acrylic Resins / Q000737:chemistry; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000378:metabolism; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003106:Colon / Q000378:metabolism*; D003692:Delayed-Action Preparations; D015195:Drug Design; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000737:chemistry / Q000378:metabolism; D008863:Microspheres; D010232:Paraffin / Q000737:chemistry; D013997:Time Factors
D000180:Acrylic Resins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D000096:Acetone; C050528:Eudragit RS; C013517:ethyl cellulose; D010232:Paraffin; D002482:Cellulose; D007213:Indomethacin