Tableting of Eudragit RS and propranolol hydrochloride solid dispersion: effect of particle size, compaction force, and plasticizer addition on drug release.
The application of a solid dispersion (SD) system of propranolol HCl and Eudragit RS was evaluated in the preparation of prolonged release tablets. The effects of SD size fraction, compaction force, and inclusion of plasticizers [namely diethylphtalate (DEP) and triethylcitrate (TEC)] on crushing strengths of matrices and release profile of drug were also investigated. The results showed that when compressed as a tablet, the SD system was more efficient in prolonging drug release than physical mixture. This effect was due to formation of much harder tablets of the SD system (crushing strength 8.5 kg) compared with those of physical mixtures (crushing strength 2.7 kg). All matrices of the SD system showed release rate patterns that were best described by the Higuchi equation. It was also shown that the rate of drug release decreased from 19.8% to 9.13% min(-1/2) as the SD size fraction decreased from 300-350 to 125-250 microm. However, further reduction of size fraction did not significantly affect tablet crushing strength and drug release rate. Increase in compaction force from 5 to 30 kN increased the crushing strength of matrices from 2.9 to 13.6 kg. However, the rate of drug release remained nearly unchanged beyond compaction pressure of 10 kN, indicating that crushing strength of matrices in the range of 8.5-13.6 kg did not affect drug release rate. The addition of 5% or 10% of either plasticizer (DEP or TEC) led to an increase in crushing strength of matrices and more retardation of drug release. This effect was more pronounced for higher concentrations of plasticizers. This effect was probably due to more plastic deformation of matrices under the compaction force, which helped matrices to retain their shape throughout the dissolution test.
Sadeghi
F
F
School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. fatemehsadeghi@hotmail.com
Afrasiabi Garekani
H
H
Goli
F
F
D000959:Antihypertensive Agents / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002951:Citrates; D003692:Delayed-Action Preparations; D010316:Particle Size; D010795:Phthalic Acids; D010968:Plasticizers; D011109:Polymethacrylic Acids / Q000008:administration & dosage*; D011433:Propranolol / Q000008:administration & dosage*; D013607:Tablets
D000959:Antihypertensive Agents; D002951:Citrates; D003692:Delayed-Action Preparations; D010795:Phthalic Acids; D010968:Plasticizers; D011109:Polymethacrylic Acids; D013607:Tablets; C038300:methylmethacrylate-methacrylic acid copolymer; C023001:ethyl citrate; D011433:Propranolol; C007379:diethyl phthalate