Effect of formulation and process variables on porosity parameters and release rates from a multi unit erosion matrix of a poorly soluble drug.
The effect of drug loading, water required for granulation and spheronization time on porosity parameters (intrusion-extrusion isotherms, pore size distribution, total pore surface area, mean pore diameter, shape and morphology of pores) and drug release rates from pellets of a poorly soluble drug was investigated. Porosity parameters were determined by mercury intrusion porosimetry. The drug loading was found to have a profound effect on the porosity parameters. Pellets with low drug loading showed increased pore surface area with small mean pore diameters and an increased number of total pores. On the other hand, pellets with high drug loading had decreased pore surface areas with larger mean pore diameters and a reduction in the total number of pores. With high drug loading, the drug release rate decreased. Water required for granulation had a direct effect on the total porosity of the pellets. Spheronization time from 2 to 10 min had a pronounced effect on porosity parameters and release rates. No changes in porosity parameters and release rates were observed from 10 to 20 min of spheronization time. It was shown that each porosity parameter investigated was well correlated with drug release rates and thus it is important to study the effect of porosity parameters in evaluating the in vitro performance of the multi-unit erosion matrix for the controlled release of a poorly soluble drug.
Mehta
K A
KA
Rohm America Inc., Piscataway, NJ 08855, USA.
Kislalioglu
M S
MS
Phuapradit
W
W
Malick
A W
AW
Shah
N H
NH
D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D017998:Leukotriene D4 / Q000037:antagonists & inhibitors; D008628:Mercury; D011109:Polymethacrylic Acids / Q000737:chemistry; D016062:Porosity; D011208:Powders; D012995:Solubility; D013499:Surface Properties; D013607:Tablets; D013844:Thiazoles / Q000008:administration & dosage / Q000737:chemistry; D017155:Wettability
D003692:Delayed-Action Preparations; D011109:Polymethacrylic Acids; D011208:Powders; D013607:Tablets; D013844:Thiazoles; C038300:methylmethacrylate-methacrylic acid copolymer; D017998:Leukotriene D4; D008628:Mercury