A Sorption Study between Ophthalmic Drugs and Multi Dose Eyedroppers in Simulated Use Conditions

Abstract

<jats:title>Abstract</jats:title><jats:p>Preservative free ophthalmic formulations need to be packaged either as single doses, or using specially designed sterility preserving multidose eyedroppers. Our objective was to evaluate potential sorption phenomena between a device with a silicone sterility preserving membrane and the delivered drops of several ophthalmic solutions. Cyclosporine, rifamycin, latanoprost, timolol and norfloxacin were used as model drugs. Quantification of the active substance in delivered drops (1 to 4 drops per day) from low density polyethylene (LDPE) bottles without any sterility preserving device and from LDPE bottles with a sterility preserving silicone membrane (LDPE-Si) was performed for 14 days (n≥3), using validated HPLC methods. For cyclosporine, mean concentrations did not vary by more than 10 % from reference concentrations for either LDPE or LDPE-Si eyedroppers, but for LDPE-Si, the concentrations of the 1 mg.ml-1 cyclosporine micellar solution were found to be significantly lower than for those from LDPE eyedroppers (p=0.0127). For LDPE-Si, rifamycin mean concentrations decreased by 11.2 % throughout the 14 day study period, but didn’t vary by more than 10 % for LDPE and glass eyedroppers. However, rifamycin concentrations from LDPE-Si were not significantly different from those from LDPE eyedroppers. For latanoprost, whilst mean concentrations did not vary by more than 10 % from reference concentration for LDPE eyedroppers, for LDPE-Si eyedroppers concentrations decreased by 76.4 % at their lowest concentration and never returned to their initial level. For timolol and norfloxacin, mean concentrations did not vary by more than 10 % for either LDPE or LDPE-Si eyedroppers and no significant difference was found between the 2 eyedroppers concentrations. Our results are in favor of an absence of significant sorption between LDPE-Si eyedroppers for timolol or norfloxacin ophthalmic solutions. Further studies should be performed on cyclosporine ophthalmic micellar solutions and rifamycin ophthalmic solutions before any definite conclusions can be made. Finally, our results show that latanoprost ophthalmic solutions shouldn’t be used with LDPE-Si eyedroppers as the loss of active substance would cause a sever under-dosing.</jats:p>

Critical Drug Loss Induced by Silicone and Polyurethane Implantable Catheters in a Simulated Infusion Setup with Three Model Drugs

“…The influence of Zeta potential on sorption capacity was previously hypothesized [ 12 ], and this result was congruent with this previous finding as the closest to zero Zeta potential was responsible for the most important loss among PUR catheters. Silicone rubber is also known to present a risk of sorption [ 11 , 18 ]. Among all of the tested catheters, the silicone one appeared to have the highest tendency to induce diazepam sorption and was also correlated with a low surface Zeta potential.…”

“…Catheters are of tantamount importance as they are implanted through the skin into the blood circulation and actually administer the drugs into the patients’ body. Unfortunately, they are almost exclusively made of polyurethane (PUR) or silicone, and these materials, despite their great biocompatibility, have been shown to be at high risk of causing drug loss by sorption [ 13 , 14 , 15 , 16 , 17 , 18 ], but these studies are few, not recent, and do not take into account the whole infusion setup.…”

Stability of Ophthalmic Atropine Solutions for Child Myopia Control

“…During the simulated use study, atropine was quantified in the emitted drops to evaluate any potential loss of API by sorption (adsorption or absorption), as it has been shown that such a phenomena can occur during the first few days of treatment initiation with certain APIs and ophthalmic delivery devices [ 49 ]. During the 6-day study, atropine concentrations in the emitted drops remained stable (no variation exceeding of ±5% of initial concentration), therefore excluding any clinically significant loss of atropine.…”

Physicochemical Stability of a Novel Tacrolimus Ophthalmic Formulation for the Treatment of Ophthalmic Inflammatory Diseases

“…During the simulated test, the overall concentrations remained stable, yet variations in tacrolimus concentrations were observed in the emitted drops, especially with the 0.2 mg/mL formulation. This could be attributed to the sorption of tacrolimus to the surface of the silicone parts in contact with the fluid path inside the Novelia ® nozzle, similar to what has already been shown for other lipophilic substances like latanoprost, and to a lesser extent, cyclosporine [55]. These variations must, however, be compared to the variable and small quantity actually absorbed by the eye after instillation [56], and they are quite possibly clinically insignificant.…”