Physiological Pharmaceutics

262 Physiological PharmaceuticsEffect of systemically administered drugsTear film dynamics can be affected by systemically administered pharmacological agents andlocally applied adjuvants. Timolol applied topically reduces tear flow whereas pilocarpinestimulates tear flow. The adjuvant benzalkonium chloride disrupts the tear film whereasmethylcellulose increases the stability of the tear film. Certain drugs can influence blink rateas well as tear secretion; for example, general anaesthetics may completely inhibit lidmovements.Drugs that are used to treat common conditions such as hypertension and allergicconditions can also influence tear film dynamics. If a patient presents with a complaintinvolving the tear film, it is important to rule out whether this is a side effect of othermedication. Antihypertensives administered systemically (e.g. reserpine, diazoxide)stimulate tear flow whilst antihistamines reduce tear flow.ROUTES OF DRUG ADMINISTRATIONThere are three main routes commonly used for administering drugs to the eye:1. Topical—drops or ointment2. Systemic—oral or injection3. Intra-ocular injectionTopical administrationDropsThe most common form of topical administration is the eye drop. It is apparently easy touse, relatively inexpensive and does not impair vision. The major problems with these typesof formulation are their inability to sustain high local concentrations of drug and they onlyhave a short contact time with the eye.Most eye-drops consist of an aqueous medium, to which can be added buffers(phosphate, borate, acetate and glucuronate), organic and inorganic excipients, emulsifiers,and wetting agents in order to accommodate a wide range of drugs with varying degrees ofpolarity. Vehicles may include water, aqueous mixtures of lower alkanols, vegetable oils,polyalkylene glycols, or petrolatum based jelly. Other excipients include ethylcellulose, ethyloleate, carboxymethylcellulose and polyvinylpyrrolidone.Contact time between the vehicle and the eye can be increased by the addition ofpolymers such as polyvinyl alcohol and methylcellulose, although generally the effects ondrug absorption are not dramatic. Drainage from the cul-de-sac may also be reduced bypunctual occlusion or simple eyelid closure, which prolongs the contact time of the drugwith the external eye. This serves two purposes- first it maximises the contact of drug withthe periocular tissues increasing absorption through the cornea and second, the systemicabsorption is reduced.PerfusionContinuous and constant perfusion of the eye with drug solutions can be achieved by theuse of ambulatory motor driven syringes that deliver drug solutions through finepolyethylene tubing positioned in the conjunctival sac. The flow rate of the perfusatethrough a minipump can be adjusted to produce continuous irrigation of the eye surface (3–6 ml.min - 1 ) or slow delivery (0.2 ml.min -1 ) to avoid overflow. This system allows the use ofa lower drug concentration than used in conventional eye-drops, yet will produce the samepotency. Side effects are reduced and constant therapeutic action is maintained. This systemis not used very often due to the inconvenience and the cost involved, but may findapplication for irritant drugs or for sight-threatening situations