From the laboratory to the end-user: a primary packaging study for microneedle patches containing amoxicillin sodium

Emma Mcalister,Ryan F Donnelly,Mary-Carmel Kearney,E Linzi Martin

doi:10.1007/s13346-020-00883-5

Emma Mcalister, Ryan F Donnelly + Show 2 more

Open Access

https://doi.org/10.1007/s13346-020-00883-5

Copy DOI

Abstract

As microneedle (MN) patches progress towards commercialisation, there is a need to address issues surrounding their translation from the laboratory to the end-user. One important aspect of MN patches moving forward is appropriate primary packaging. This research focuses on MN patches containing amoxicillin (AMX) sodium for the potential treatment of neonatal sepsis in hot and humid countries. A MN patch consists of a hydrogel-forming MN array and a drug-containing reservoir. Improper primary packaging in hot and humid countries may result in degradation of active pharmaceutical ingredients, with the use of substandard medicines a major health concern. The research presented here, for the first time, seeks to investigate the integrity of MN patches in different primary packaging when stored under accelerated storage conditions, according to international guidelines. At pre-defined intervals, the performance of the MN patch was investigated. Major causes of drug instability are moisture and temperature. To avoid unnecessary degradation, suitable primary packaging was sought. After 168 days, the percentage of AMX sodium recovered from drug-containing reservoirs packaged in Protect™ 470 foil was 103.51 ± 7.03%. However, packaged in poly(ester) foil, the AMX sodium content decreased significantly (p = 0.0286), which is likely due to the degradation of AMX sodium by the imbibed moisture. Therefore, convincing evidence was provided as to the importance of investigating the stability of MN patches in primary packaging intended for MN-mediated transdermal delivery so that they are ‘fit for purpose’ when it reaches the end-user. Future work will include qualitative studies to assess MN patch usability.Graphical abstract

Highlights

Microneedle (MN) arrays are minimally invasive devices that can painlessly bypass the stratum corneum (SC) and generate mechanical microchannels to facilitate drug delivery [1,2,3]
The stability testing of MN patches, hydrogel-forming MN arrays and AMX sodium directly compressed tablets (DCTs) was evaluated under accelerated storage conditions
There were three cohorts; one cohort packaged in ProtectTM 470 foil (Fig. 3a), one cohort packaged in poly(ester) foil (Fig. 3b) and one cohort as the control which was unpackaged

Summary

Introduction

Microneedle (MN) arrays are minimally invasive devices that can painlessly bypass the stratum corneum (SC) and generate mechanical microchannels to facilitate drug delivery [1,2,3]. Comprised of chemically cross-linked hydrophilic polymer matrices [6], hydrogel-forming MN arrays are hard and sharp in the dry state. In this drug delivery strategy, the drug molecule to be delivered is not within the hydrogel-forming. MN array but in a separate drug-containing reservoir. The moisture from the swellable MN array comes in contact and subsequently triggers diffusion of the drug molecule from the attached drug-containing reservoir through the hydrogel matrix. This unique MN array design has its own advantages [8]. An extensive number of studies have been published, showing the capabilities of hydrogel-forming MN arrays to transdermally deliver both small molecular weight drug molecules and macromolecules [8,9,10,11,12]

Methods

Results

Discussion

Conclusion