Validation of tablet dissolution method by high-performance liquid chromatography.
Dissolution is a qualitative and quantitative tool that can provide valuable information about biological availability of a drug, as well as batch-to-batch consistency. It is considered one of the most important quality control tests performed on pharmaceutical dosage forms, and validation of dissolution methods is an important part of good manufacturing practices (GMP). Hydroxypropylcellulose (HPC) was formulated with acetaminophen (APAP) and hydrochlorothiazide (HCTZ). Dissolution methods and limits are reported in the USP/NF. Standard operating procedures (SOP) for the HP 8452A spectrophotometer and Vanderkamp 600/6010 Dissolution Tester were followed according to the GMP Manual. A dissolution method was developed for each formulation based on the above. The only discrepancy between high-performance liquid chromatography (HPLC) and standard dissolution testing occurred when comparing the results of the HPC/HCTZ formulation. The ultraviolet (UV) samples were filtered through a 10-micron filter, and the HPLC samples were filtered through a 0.2-micron filter. When the HPC/HCTZ samples were filtered through a 10-micron filter for both UV and liquid chromatography (LC), the results were equal. Filter pore size and area have a large effect on concentration of HPC/HCTZ. The smaller the pore size and the smaller the diameter of the filter, the more HPC/HCTZ is filtered out. HCTZ has a greater tendency to interact with HPC in the filter than other active ingredients tested. HPC and HCTZ levels have little or no effect on the amount of HCTZ lost.
Guo
J H
JH
Hercules Incorporated, Wilmington, DE 19808, USA. guo@brk.bf'g.com
Harcum
W W
WW
Skinner
G W
GW
Dluzneski
P R
PR
Trumbull
D E
DE
D000082:Acetaminophen / Q000493:pharmacokinetics; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000592:standards*; D004232:Diuretics; D005374:Filtration; D006852:Hydrochlorothiazide / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D049993:Sodium Chloride Symporter Inhibitors / Q000493:pharmacokinetics; D012995:Solubility; D013607:Tablets
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D013607:Tablets; D006852:Hydrochlorothiazide; D000082:Acetaminophen; D002482:Cellulose; C008079:hydroxypropylcellulose