The design of contact lens based ocular drug delivery systems for single-day use: Part (I) Structural factors, surrogate ophthalmic dyes and passive diffusion studies

Abstract

The poor retention and efficacy of instilled drops as a means of delivering drugs to the ophthalmic environment is well-recognised. The potential value of contact lenses as a means of ophthalmic drug delivery and consequent improvement of pre-corneal retention is one obvious route to the development of a more effective ocular delivery system. Furthermore, the increasing availability and clinical use of daily disposable contact lenses provides the platform for the development of viable single-day use drug delivery devices based on existing materials and lenses. In order to provide a basis for the effective design of such devices, a systematic understanding of the factors affecting the interaction of individual drugs with the lens matrix is required. Because a large number of potential structural variables are involved it is necessary to achieve some rationalisation of the parameters and physicochemical properties (such as molecular weight, charge, partition coefficients) that influence drug interactions. Ophthalmic dyes and structurally related compounds based on the same core structure were used to investigate these various factors and the way in which they can be used in concert to design effective release systems for structurally different drugs. Initial studies of passive diffusional release form a necessary precursor to the investigation of the features of the ocular environment that over-ride this simple behaviour. Commercially available contact lenses of differing structural classifications were used to study factors affecting the uptake of the surrogate actives and their release under "passive" conditions. The interaction between active and lens material shows considerable and complex structure dependence which is not simply related to equilibrium water content (EWC). The structure of the polymer matrix itself was found to have the dominant controlling influence on active uptake; hydrophobic interaction with the ophthalmic dye playing a major role.3

Structural design of contact lens-based drug delivery systems; in vitro and in vivo studies of ocular triggering mechanisms

“…Figure 3 shows that the greater interaction of Bromopyrogallol Red with HEMA-NVP results in a higher level of dye uptake coupled with both a greater mass of dye released and a greater quantity of dye retained. Previous experiments [1,29] have shown marked differences in drug uptake with different polymer matrices, but here we see that polymer structure can additionally influence the mass and proportion of dye retained when passive diffusion has reached equilibrium. This is an extremely important point in relation to the exploitation of contact lenses as delivery reservoirs for ophthalmic drugs.…”

“…Details of the materials used and the procedures followed for incorporating an active into a lens, passive release and analysis of the release media have been previously published [1]. The range of ophthalmic dyes and structurally related compounds used in this study are based on the same core structure (Figure 1), which is shared by key ophthalmic dyes such as Rose Bengal, Lissamine Green B and sodium fluorescein.…”

“…The range of substituents, octanol-water partition and distribution coefficients and molecular weights of this family of compounds is shown in Table 1. The shared multi ring core structure is a common feature of many drug systems [1], which have hydrophobicity arising from the aromatic ring systems and hydrophilicity from functional groups. The use of ophthalmic dyes as models indicate the relative influence of the balance of hydrophobicity and hydrophilicity and also relative steric effects which lead to association.…”

“…The inefficiency of direct instillation as a delivery method for ophthalmic drugs is well-recognised, as is the potential value of contact lenses for this application [1,2]. Despite this, there are virtually no commercial examples of this area of technology.…”

“…Although a number of in vitro studies almost exclusively based on uptake and passive release behaviour of ophthalmic drugs from contact lenses have been carried out [1,[28][29][30], there has been little attempt to mimic the particular features of the ocular environment. This paper uses the understanding of drug-lens interactions developed from equilibrium passive release studies and 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 3 retention in the design of effective in-eye delivery systems.…”