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. 2023 Nov 5;15(11):2589.
doi: 10.3390/pharmaceutics15112589.

Cysteamine Eye Drops in Hyaluronic Acid Packaged in Innovative Single-Dose Systems, Part II: Long-Term Stability and Clinical Ocular Biopermanence

Ana Castro-Balado  1   2   3 , Andrea Cuartero-Martínez  2 , Hugo Pena-Verdeal  4   5 , Gonzalo Hermelo-Vidal  2 , Anja Schmidt  6 , Belén Montero  6 , Manuela Hernández-Blanco  7 , Irene Zarra-Ferro  1   2 , Miguel González-Barcia  1   2 , Cristina Mondelo-García  1   2 , María Jesús Giráldez  4   5 , Eva Yebra-Pimentel  4   5 , Francisco J Otero-Espinar  3 , Anxo Fernández-Ferreiro  1   2
Affiliations

Cysteamine Eye Drops in Hyaluronic Acid Packaged in Innovative Single-Dose Systems, Part II: Long-Term Stability and Clinical Ocular Biopermanence

Ana Castro-Balado et al. Pharmaceutics. .

Abstract

Background: Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in several tissues and organs causing, among others, severe eye symptoms. The high instability of cysteamine eye drops makes it difficult to develop formulations with an acceptable shelf life to be prepared in hospital pharmacy departments. Previously, a new compounded formulation of cysteamine eye drops in hyaluronic acid (HA) packaged in innovative single-dose systems was developed.

Methods: Long-term stability at -20 °C of this formulation was studied considering the content of cysteamine, pH, osmolality, viscosity, and microbiological analysis. The oxygen permeability of single-dose containers was also studied and an ocular biopermanence study was conducted in healthy volunteers measuring lacrimal stability and volume parameters.

Results: Data confirm that cysteamine concentration remained above 90% for 120 days, all parameters remaining within the accepted range for ophthalmic formulations. The permeability of the containers was reduced over time, while ocular biopermanence was maintained despite the freezing process and storage time.

Conclusions: 0.55% cysteamine hydrochloride formulation in HA and packaged in single-dose containers preserved at -20 °C is stable for 120 days protected from light, presenting high potential for its translation into clinical practice when commercial presentations are not available.

Keywords: cysteamine; cystinosis; eye drops; ophthalmic administration.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Cysteamine content (%) with respect to day 0 of the cysteamine compounded formulation stored at −20 °C for 120 days protected from light at day 0 (unfrozen formulation) and days 30, 60, 90 and 120 post-freezing.
Figure 2
Figure 2
Variation in pH and osmolality (mOsm/kg) of the cysteamine formulation measured at day 0 (unfrozen formulation) and at days 30, 60, 90 and 120 post-freezing: (a) pH; (b) osmolality.
Figure 3
Figure 3
Viscosity of the cysteamine compounded formulation values measured at day 0 (unfrozen formulation) and at days 30 and 120 post-freezing. Measurements were made at 25 °C and 100 revolutions per minute (rpm). * statistical significance p < 0.05.
Figure 4
Figure 4
Oxygen transmission rate variation of the single-dose vials on days 0 (unfrozen formulation), 30 and 120 post-freezing.
Figure 5
Figure 5
Vertical measurement of TMH in one of the healthy volunteers. (a) TMH before the instillation; (b) TMH 2 min after the instillation of the 30-day frozen formulation.
Figure 6
Figure 6
Representative image of NIKBUT. The red mark indicates the disruption on the tear film when breakup time was registered.
Figure 7
Figure 7
Mean values of the measurement time-points at different conditions. Day 0: unfrozen formulation; Day 30: 30-day frozen formulation; Day 120: 120-day frozen formulation. (a) Tear meniscus height (TMH); (b) Non-invasive keratograph tear breakup time (NIKBUT).
See this image and copyright information in PMC

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