INTRODUCTION
It is known that during the instillation of eye drops, a number of therapeutic problems arise: because of the frequency of the instillation themselves, irritation of the mucous membrane of the eye is possible, the action of drug agents is limited to the anterior chamber of the eye, etc. In addition, leakage of a part of the administered drug from the conjunctival sac and its elimination through the tear duct should be taken into account, which reduces the effectiveness of pharmacotherapy [1]. In turn, soft contact lenses (SCL), used as a means of delivery of pharmacological agents, regulate the continuous release of an active pharmaceutical ingredient (API) during the entire time of contact of the ophthalmic therapeutic system “SCL: medicinal composition” with cornea eyes. Early studies of the prolongation of the action of eye drops using various types of contact lenses showed the advantages of this technical solution. This is the non-invasiveness of the method, the willingness of patients to follow the usual contact correction, the possibility of combined treatment and correction of ametropia, etc. These approaches have been improved with the advent of new materials for SCL, especially with the appearance of hydrophilic polymers with increased moisture content [2]. For example, J.B. Ciolino et al. used SCL with latanoprost on monkeys. It was found that in the case of the use of SCL, intraocular pressure during the day was more stable than with the instillation regimen [3]. C.C. Peng et al. used silicone SCL soaked in timolol and vitamin E on dogs with simulated glaucoma. The levels of lowering intraocular pressure when using MCL and eye drops were comparable [4]. F. A. Maulvi et al. in the manufacture of SCL, gold nanoparticles were included in its structure in order to increase the incorporated amount of timolol maleate and its faster release. The kinetics of the release of timolol from SCL in an in vivo experiment (rabbits) showed a longer hypotensive effect under the same conditions of saturation with a solution of timolol SCL with and without gold nanoparticles [5]. Thus, the prospect of such studies is beyond doubt, especially in the age of excessive load on the human organ of vision. The purpose of this preliminary fragment of large-scale studies was to study the process of release of a number of drug compounds in model solutions from the surface of SCL from various materials. There are many innovations on therapeutic contact lenses to treat anterior ocular diseases which uses soaking method, molecular imprinting, entrapment of drug-laden colloidal nanoparticles, drug plate, ion ligand polymeric systems, supercritical fluid technology, etc [6-9]. Colloidal nanoparticles laden therapeutic contact lens technique is based on the ability of colloidal nanoparticles (polymeric nanoparticles, liposomes, niosomes, micro-emulsion, micelles, etc.) to entrap or encapsulate drug and control its release rate from contact lenses. Such formulated nanoparticular system (10 to 100 nm) is dispersed in HEMA monomers and polymerized using ethylene glycol-dimetha-crylate (EGDMA) and photo initiator (DarocurÕ) to fabricate therapeutic contact lenses. Drug laden nanoparticles prevent the interaction of drug with polymerization mixture and also offer additional resistance to drug release. Thus the nanoparticles loaded contact lenses can deliver drugs at controlled rate for extended period of time. Drug loaded nanoparticles or globules (microemulsion) also bypass, to some extent, drug metabolism from the enzymes like lysosomes, present in the tear/corneal epithelial surface. The researchers have being successful in developing therapeutic contact lenses for extended drug delivery, while at the same time the transparency (optical), oxygen permeability, ion permeability, mechanical properties, and swelling behavior of contact lenses was altered for comfort wear [10-13]. First method developed to load drugs into contact lenses was by soaking contact lenses in drug solutions, but nearly all the drug in contact lenses was released within 1–3 h [14-17]. To overcome this drawback, many techniques to design therapeutic contact lenses have been developed, including a molecular imprinting technique, the entrapment of drug-loaded colloidal micro- and nanoparticles, drug-loaded implants in the contact lenses, sustained drug release using ionic interactions, drug delivery with vitamin E diffusion barriers, and supercritical fluid technology [18–21].

MATERIALS AND METHODS
The following types of soft contact lenses were purchased for this study: Dailies AquaComfort Plus» (nelfilcon A); Bausch&Lomb «SofLens Daily Disposable» (hilafilcon B); Bausch&Lomb «BioTrue One-day» (nesofilcon A); Johnson & Johnson «Acuvue 1-Day Moist» (etafilcon A); Alcon «Air Optix Colors» (lotrafilcon B). For this study, the following active pharmaceutical substances were used: brimonidine tartrate (NDA 20613/S-031), Betaxolol hydrochloride (EP 8.0 07/2011:1072), pyridoxine hydrochloride (EP 8.0 01/2010:0245). The following model solutions were used in the work, selected from the line of those studied by technological priorities (working numbering of samples was kept): Model solution 1: brimonidine tartrate 0.006 g; pyridoxine hydrochloride 0.009 g; sodium hyaluronate 0.015 g; water purified for injetions up to 3 mL. Model solution 2: betaxolol hydrochloride 0.017 g; pyridoxine hydrochloride 0.009 g; sodium hyaluronate 0.015 g; water purified for injetions up to 3 mL. Quantitative determination of brimonidine tartrate in model solutions for the saturation of SCL [22]. To conduct the identification and assay tests on brimonidine tartrate in model solutions, a spectrophotometer SF-104. 1 ml of the model solution was transferred using an automatic pipette into a 200 ml volumetric flask, 5 ml of purified water was added thereto with the same pipette to completely transfer the active pharmaceutical substance. The solution was slightly shaken, after which its volume was led up to 200 ml with the same solvent, followed by shaking. The optical density was measured using the following instrument settings: wavelength range 220-310 nm, optical density axis ranges 0.000-1.000, fast measurement mode. The conclusion about the identification test of brimonidine tartrate was made based on the absorption maximum at 247 ± 1 nm. The optical density at this wavelength was taken to calculate the quantitative content of the substance in the solution according to the specific absorption coefficient, using the below formula.

Where X is concentration of brimonidine tartrate in a sample (%), 200 is dissolution rate, A – optical density of a sample at 247 nm, E1CM is specific absorption coefficient, 588, l is optical path length, cm. Quantitative determination of betaxolol hydrochloride in model solutions for the saturation of SCL. To conduct the identification and assay tests on betaxolol hydrochloride in the model solution, the same sample preparation algorithm and analysis conditions were used as for brimonidine tartrate, but an aliquot volume was dissolved in 50 ml of purified water. The quantitative content of betaxolol hydrochloride was calculated according to formula 1 using the specific absorption coefficient equal to 38 and the actual determined optical density, which was observed at 274 ± 1 nm. Quantitative determination of pyridoxine hydrochloride in model solutions for the saturation of SCL. To conduct the identification and assay tests on pyridoxine hydrochloride in the model solution, the same sample preparation algorithm and analysis conditions were used as for brimonidine tartrate. The quantitative content of pyridoxine hydrochloride was calculated according to formula 1 using the specific absorption coefficient equal to 313 and the actual determined optical density, which was observed at 292 ± 1 nm.

RESULTS AND DISCUSSIONS
In the process of developing the composition and technology of an ophthalmic system based on SCL, special attention should be paid to the duration and completeness of the process of API release from the surface of the SCL to the surface of the affected eye [23]. The results of a study of API release of model ophthalmic solutions from the surface of SCL are presented in Figs. 1-4.
As can be seen from Fig. 1, the release of brimonidine tartrate model solution 1 from SCL occurs within one hour. The amount of drug released into the solution simulating the environment of the eye tissues was 98.13-99.35% of the previously absorbed amount. Moreover, the most complete (99.35%) release of brimonidine tartrate is characteristic of MCLs made from hilafilcon B. The smallest amount (98.13%) of the drug was resolved into the solution from the surface of SCL from nesofilcon A. All SCL materials are characterized by a more intense release of the model solution from the surface during the first 30 minutes of the experiment, after which the process speed was significantly slowed down.
Fig. 2 shows that the release profile of pyridoxine hydrochloride model solution 1 from SCL is absolutely identical to the release profile of brimonidine tartrate. Namely, the release of pyridoxine hydrochloride most fully passed from the surface of SCLs prepared from hilafilcon B and amounted to 99.35% or 0.229 mg. 0.236 mg (98.13%) of the previously absorbed drug transferred from the surface of the SCL from nesofilcon A to the receiver solution.
All MKL materials are characterized by a more intensive release of the model solution from the surface during the first 30 minutes of the experiment, after which the process speed was significantly slowed down.
As can be seen in Fig. 3, the release of betaxolol hydrochloride in model solution 2 from SCL also takes place within one hour. The release profiles differ significantly for each SCL material: the release process is less intensive (0.215 mg; 92.27%) for lotrafilcon B, but most fully (0.285 mg; 95.96%) for hilafilcon B.
All SCL materials are characterized by a more intensive release of the model solution from the surface during the first 30 minutes of the experiment, after which the process speed was significantly slowed down.
From the data shown in Fig. 4, it can be seen that the release profile of pyridoxine hydrochloride of model solution 2 is identical to the release profile of betaxolol hydrochloride. The release of pyridoxine hydrochloride most fully passed from the surface of SCLs prepared from chilafilcon B, and amounted to 95.96% or 0.156 mg. 0.236 mg, or 98.13% of the previously absorbed API, passed from the surface of the SCL from nesofilcon A to the receiver solution. In addition, all SCL materials are characterized by a more intense release of the model solution from the surface during the first 30 minutes of the experiment, after which the process speed was significantly slowed down. An important stage in the study of SCL of various materials as a means of prolonged drug delivery is a comparative assessment of the quantities of released active components from the surface of the SCL. You should also take into account such an indicator of the ophthalmic transport system as the time of drug release from the surface of the SCL. In turn, for eye drops, such performance indicators as the time of presence of a drug on the surface of the eye and the minimum amount of drug needed to provide a therapeutic effect are important.
According to published data, the time of the presence of ophthalmic solutions on the surface of the eye, as a rule, does not exceed 3 minutes [1-4]. Data on the minimum required amounts of anti-glaucoma drugs to provide a therapeutic effect were obtained from official instructions for the use of drugs and the results of a study on the release of drugs from SCL are presented in Table 1.
As can be seen from the data given in Table 1, brimonidine tartrate and pyridoxine hydrochloride model ophthalmic solution 1 after the release of all the studied materials from the surface of the SCL were found in 0.9% NaCl in amounts exceeding the minimum therapeutic. This tentatively suggests that model solution 1 and the studied SCL can be used together as a single ophthalmic therapeutic system. However, for betaxolol hydrochloride and pyridoxine hydrochloride model ophthalmic solution 2, it was found that the process of drug release from the surface of the studied SCL was slightly higher than therapeutic amounts for nelfilcon A alone, amounting to 0.285 and 0.156 mg, respectively. The release of the remaining materials from the SCL surfaces was insufficient. Thus, the use of ophthalmic model solution 2 as part of an ophthalmic therapeutic system is irrational, since it is limited by the possibility of using only with SCL made from nelfilcon A. In addition, the assessment of the processes of saturation and release of SCL is not a predetermining experiment, on the basis of the results of which it can be concluded that the use of one or another composition of the ophthalmic transport system is rational. The final conclusion about the possibility of using a certain composition of a model ophthalmic solution in an ophthalmic transport system can be made only based on the results of biopharmaceutical studies, which involve studying the time and completeness of the passage of active drugs through biological tissue barriers.

CONCLUSION
In the frame of the current study it was feasible to prove that such method of drug loading of SCL as soaking is still relevant. The advantage of studied material of soft contact lenses was demonstrated versus other, highly technological methods such as loading with colloidal particles, binding of molecules of active pharmaceutical substance to the structure of SCL, etc. The main advantage of covering the SCL with mucoadgesive therapeutic solution is its independence on type of surface of soft contact lenses. However, the achieved results are not the finishing point in development of composition of solution for SCL saturation. It’s believed, that composition somehow can be adjusted in certain way, when release of therapeutic molecules will last longer than 60 minutes and, thus, will be more accurately controlled. In addition, the assessment of the processes of saturation and release of SCL is not a predetermining experiment, on the basis of the results of which it can be concluded that the use of one or another composition of the ophthalmic transport system is rational. The final conclusion about the possibility of using a certain composition of a model ophthalmic solution in an ophthalmic transport system can be made only based on the results of biopharmaceutical studies, which involve studying the time and completeness of the passage of active drugs through biological tissue barriers. However, the deeper knowledge can be obtained if more advanced approach is applied to biopharmaceutical study of API release.

CONFLICT OF INTEREST
The authors declare that there is no conflict of interests regarding the publication of this manuscript.