Development of an ophthalmic solution combining allogenic plasma with protective excipients for enhanced therapeutic role in the management of ocular surface diseases

Abstract

Ocular surface diseases (OSDs) are characterised by an instability of the tear film. In severe cases, these disorders have been improved by using human serum or plasma formulated into eye drops. These blood-derived-products present a biological composition similar to that of tears and contain beneficial factors that modulate inflammation and tissue regeneration. However, the supply of blood derivatives remains a challenge due to the potential microbiological risk, the quality and inter-individual heterogeneity of the biological samples used, and logistical difficulties. Thus, the idea behind this work was to use a standardised blood-derived product produced and checked industrially from a pool of donors, and to combine it with protective excipients known for their lubricating, anti-inflammatory, and regenerative properties offering new treatment opportunities for OSDs. Attention was also given to the non-bioaccumulative nature of the excipients. In order to select the concentrations of different compounds of interest in the ophthalmic solution, a design of experiment was used to establish a formulation with physicochemical properties (pH, osmolality, turbidity, viscosity) compatible with good ocular tolerance. Once defined, a physicochemical stability study testing pH, osmolality and dosage of biological factors, was carried out using the storage conditions usually used in clinical practice. A comparator without the additional compounds was also tested. The final formulation consisted of 20 % allogenic plasma, 0.5 % sodium hyaluronate (HS), 3 % trehalose (TH), 0.2 % chondroitin sulfate (CS) and 0.5 % sodium chloride (NaCl) (m/v). Its physicochemical properties should allow for good ocular tolerance. The data from the preliminary stability study favours storage at -20 °C for some of the biological factors measured.

Keywords: Chondroitin; Formulation; Ocular surface disease; Ophthalmic solution; Plasma; Protective excipients; Sodium hyaluronate; Trehalose.