Development and validation of UV–Vis spectrophotometry-colorimetric method for the specific quantification of rivastigmine tartrate from separable effervescent microneedles: Ex vivo and in vivo applications in complex biological matrices

Abstract

Rivastigmine Tartrate is an acetylcholinesterase inhibitor commonly used in Alzheimer treatment. Due to its hydrophilicity, short plasma elimination half-time, and poor blood-brain barrier penetration, developing a new drug delivery system for RT administration is essential. Accordingly, microneedles offer several advantages and could be a promising drug delivery system for RT administration. One of those types of MNs with numerous advantages is separable-effervescent microneedles. To support the formulation development, an analytical method using UV–Vis spectrophotometry was validated in phosphate buffered saline media and various biological matrices, such as rat skin, brain, and plasma to measure the amount of RT in the SEMNs preparations. The developed analytical method was validated under ICH guidelines. The results showed that the instrument could specifically detect the RT in the preparations without being interfered with by other compounds. The calibration curves in various biological matrices were linear ≥ 0.9985. The LOD and LLOQ values of the PBS media biological matrices were found to be 1.5 and 4.8 µg/mL, 1.2 and 3.7 µg/mL, 0.42 and 1.27 µg/mL, and 0.38 and 1.16 µg/mL, respectively. All the accuracy and precision values of this developed method were within acceptable ranges. Additionally, the extraction recovery was prominent after undergoing the protein precipitation process. As a result, the analytical method was proven to be valid and was successfully applied to quantify the amount of RT in the SEMNs formulation, in vitro and ex vivo permeation, along with in vivo pharmacokinetic studies.