Effect of compression pressure on physical properties and dissolution characteristics of disintegrating tablets of propranolol microspheres.
Propranolol HCl was encapsulated with cellulose acetate butyrate by an emulsion-solvent evaporation method. Three direct compression diluents were blended with appropriate size fractions of the microspheres and each formulation was compressed at several pressures to give tablets that readily disintegrated in water. Tablets with microcrystalline cellulose (MC) as the diluent had the highest tablet crushing strength at any given compression pressure. Heckel plots of all the microsphere-diluent blends were nonlinear, indicating that the consolidation may result from crushing and rearrangement of the individual particles in addition to plastic deformation. Tablet properties and estimated yield pressures showed that MC was the most suitable diluent for compression of propranolol HCl microspheres. Drug release from compressed tablets was always faster than from uncompressed microspheres, but useful sustained-release characteristics were retained. Dissolution tests of MC formulations of the tableted microspheres showed increased release rate constants and decreased 50 per cent dissolution times compared to microspheres that had not been compressed. This result indicated that rupture of some of the microspheres had occurred. The drug release rate increased at higher compression pressures due to the rupture of a greater proportion of microspheres. Larger changes in release rate and t50 percent were observed with larger microspheres sizes. Generally, the least compression pressure that gives tablets with acceptable properties is preferred.
Chiao
C S
CS
ANDA SR Pharmaceuticals, Davie, FL 33314.
Price
J C
JC
D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D008863:Microspheres; D010316:Particle Size; D011312:Pressure; D011433:Propranolol / Q000008:administration & dosage / Q000737:chemistry*; D013607:Tablets
D013607:Tablets; D002482:Cellulose; C014396:cellulose acetate-butyrate; D011433:Propranolol