Diagnosis of Agglomeration and Crystallinity of Active Pharmaceutical Ingredients in Over the Counter Headache Medication by Electrospray Laser Desorption Ionization Mass Spectrometry Imaging.

Mariann Inga Van Meter,Brynne V Taulbee-Cotton,Patrick A Mcvey,Nathan D Hubbard,Gregory K Webster,Nathan H Dimmitt,Salah M Khan,Adam M Green

doi:10.3390/molecules26030610

Abstract

Agglomeration of active pharmaceutical ingredients (API) in tablets can lead to decreased bioavailability in some enabling formulations. In a previous study, we determined that crystalline APIs can be detected as agglomeration in tablets formulated with amorphous acetaminophen tablets. Multiple method advancements are presented to better resolve agglomeration caused by crystallinity in standard tablets. In this study, we also evaluate three “budget” over-the-counter headache medications (subsequently labeled as brands A, B, and C) for agglomeration of the three APIs in the formulation: Acetaminophen, aspirin, and caffeine. Electrospray laser desorption ionization mass spectrometry imaging (ELDI-MSI) was used to diagnose agglomeration in the tablets by creating molecular images and observing the spatial distributions of the APIs. Brand A had virtually no agglomeration or clustering of the active ingredients. Brand B had extensive clustering of aspirin and caffeine, but acetaminophen was observed in near equal abundance across the tablet. Brand C also had extensive clustering of aspirin and caffeine, and minor clustering of acetaminophen. These results show that agglomeration with active ingredients in over-the-counter tablets can be simultaneously detected using ELDI-MS imaging.

Highlights

IntroductionQuality control of the active pharmaceutical ingredient (API) in tablets is important to maintain optimal bioavailability of the API(s) [1,2,3]
Mass spectrometry (MS) imaging was used to detect the crystalline form of an active pharmaceutical ingredient (API) in the presence of its amorphous form used in an enabling tablet formulation [4]
Crystallinity can be an issue for BCS Class II/IV drugs if the active drug has a significant difference in kinetic solubility between the crystalline and amorphous forms [5,6]

Summary

Introduction

Quality control of the active pharmaceutical ingredient (API) in tablets is important to maintain optimal bioavailability of the API(s) [1,2,3]. Mass spectrometry (MS) imaging was used to detect the crystalline form of an active pharmaceutical ingredient (API) in the presence of its amorphous form used in an enabling tablet formulation [4]. Many amorphous forms of poorly soluble drugs go into solution faster than their crystalline forms and this kinetic solubility makes the amorphous form more bioavailable. In these enabling formulations, the presence of crystalline API could be less bioavailable, and its presence makes the tablet less potent

Methods

Results

Conclusion