QUANTITATIVE DETERMINATION OF TERBINAFINE RESIDUES ON THE PHARMACEUTICAL MANUFACTURING EQUIPMENT SURFACES

Abstract

Background: Cleaning validation is a critical analytical responsibility required by GMP (Good Manufacturing Practice), which confirms the effectiveness of the cleaning standard procedure in the pharmaceutical manufacturing process for all the produced drug products contacting the shared pharmaceutical manufacturing equipment. The need to carry out cleaning validation is especially important when the drug product is the “worst-case” for the cleaning procedure regarding solubility, therapeutic potency, toxicity, and surface adherence of active pharmaceutical ingredients (API). Estimation of API residues requires a selective and sensitive method capable of quantitative determination of API traces remaining over the surface of manufacturing equipment after the cleaning procedure. Aim: The present study demonstrates the suitability and the applicability of the proposed method obtained with a combination of a sensitive, selective, and specific analytical HPLC and effective swab wipe sampling procedures for quantitative estimation of terbinafine residues in samples collected from pharmaceutical manufacturing equipment surfaces and the efficiency of the developed standard procedure for cleaning of the shared manufacturing equipment in support of cleaning validation. Methods: The swab sampling procedure was developed to obtain a suitable recovery (>80 %). The surface (sampling area – 25 cm2) was wiped with one swab moistened with methanol. The analytical procedure was developed using the HPLC system “Agilent 1260 Infinity II” and BDS Hypersil C18 250×4.6 mm, 5 ?m column with an isocratic elution of mobile phase. Results and Discussion: The developed combined method was validated concerning chromatographic system suitability test, specificity, linearity range, accuracy, precision, the limit of detection (LOD), and quantitation (LOQ). The stability of terbinafine HCl solutions in methanol, the swab material, and membrane filter compatibility was also studied. The calibration curve was linear (R2=0.99999) over a concentration range 0.00003-0.025 mg/mL; LOD – 0.000015 mg/mL, and LOQ – 0.00003 mg/mL; The determined concentrations of terbinafine residues in test solutions were not more than 0.00090 mg/mL which are below the limit of cross-contamination of the next drug product. Conclusions: The performed analytical study using the developed method with a combination of an analytical HPLC and swab sampling procedures for estimation of terbinafine residues on surfaces of the pharmaceutical equipment used during the manufacture of Terbinafine HCl 250 mg uncoated tablets demonstrates the validity of the cleaning procedure. Other quality control laboratories can apply the proposed method to carry out cleaning validation on various drug formulations of terbinafine HCl.