eye drop

Drop bottle

One-dose ophtiols

Eye drops ( Oculoguttae ) are a dosage form for liquid preparations to be instilled in the conjunctival sac or on the cornea of the eye . It can be aqueous or oily solutions, emulsions or suspensions . Eye drops act locally . Typical areas of application are the treatment of dryness and irritation of the eye, glaucoma ( glaucoma ), as well as conjunctivitis ( conjunctivitis ) and corneal inflammation ( keratitis ).

Eye drops with a medicinal effect are drugs , those with physiological or physical effects are medical products .

In addition to industrial production, eye drops can also be produced according to prescriptions in pharmacies.

application

Typical areas of application are the treatment of dryness and irritation of the eye, in some cases purely moisturizing, physically acting preparations are used which, due to their increased viscosity, form a film that remains in the eye for a relatively long time and reduce mechanical friction and evaporation of tear fluid. Cellulose derivatives, polyvinylpyrrolidone , carbomer , polyvinyl alcohols and combinations with lipids are used as film formers .

Other areas of application are glaucoma , conjunctivides and keratitis. Eye drops have a local effect, which is an advantage since the eye is difficult to reach systemically. Local administration has better selectivity than systemic administration and higher drug concentrations can be achieved.

conditions

Sterility

According to the regulation of the European Pharmacopoeia (Ph. Eur.) , Eye drops must be sterile , as the eye is a sensitive sensory organ that is not well supplied with blood and its possibilities for regeneration are limited.

compatibility

In order to achieve the best possible effectiveness, tolerability and lack of irritation when using eye drops, the pH value , tonicity and viscosity of the eye drops must be adapted as far as possible to the physiological parameters of the tear film . This is especially necessary with aqueous eye drop solutions.

• pH value: Eye drops should ideally have a physiological pH value between 7.1 and 7.5 ( isohydria ). Buffer systems such as sodium acetate / boric acid , phosphate or acetate buffers can be used for setting . If active ingredients are not sufficiently chemically stable under these pH conditions, the pH value of the eye drops is adjusted with acids or alkalis in such a way that optimal stability of the active ingredient is achieved, and the pH value is nevertheless in the physiologically tolerable, euhydric range of 7.1 to 9.7. After introduction into the eye, the pH value is adjusted to the physiological pH value by the buffer effect of the tear fluid. Outside the isohydric pH value, eye drops should not be buffered , as the buffer capacity of the protein / phosphate and bicarbonate buffers present in the tear fluid is only very small and no adjustment to the physiological pH value is possible.
  For active ingredients such as timolol or pilocarpine , which have their maximum stability at non-physiologically acidic pH values, a two-chamber system, the contents of which are mixed before use, can ensure stability and tolerability.

• Tonicity: For irritation-free tolerance, an osmotic pressure ( isotonicity ) corresponding to the corneal epithelium must also be set, corresponding to a sodium chloride concentration of 0.9% or an osmolality of 250 to 300 mosm / kg. 225–430 mosm / kg are considered painlessly tolerated. Hypertonic solutions are better tolerated than hypotonic ones. Some indications require therapeutically effective concentrations of drugs that lead to hypertonic solutions.
  The tonicity is adjusted with isotonic agents such as B. sodium chloride, potassium nitrate , boric acid , sodium acetate or mannitol .

Containers and preservation

Administration with the patient lying down

Eye drops are filled either in eye drop bottles made of special glass (amber glass type I ) or in plastic containers ( ophtiols ). Ophtioles are available for single use (single-dose ophthalmic, EDO) or for multiple use (multi-dose ophthalmic, MDO). Multi-dose containers allow the preparation to be applied dropwise several times and contain a maximum volume of 10 ml.

In order to suppress microbial contamination after opening, aqueous eye drops must be preserved in multi-dose containers, unless the preparation itself already has antimicrobial properties or the container construction prevents the penetration of germs. The aqueous phase of emulsions must also be adequately preserved. Common preservatives are:

• Thiomersal 0.002%
• Organic mercury compounds phenyl mercury
• Benzalkonium chloride 0.002-0.02% (quaternary ammonium compounds / quaternary ammonium salts)
• Chlorhexidine 0.005-0.01%
• Benzyl alcohol 0.5–1%

Eye drops for use before or during surgical procedures must not contain preservatives.

Multi-dose containers that prevent microbial contamination of the preparation after opening so that preservatives are necessary are, for example, the ABAK® primary pack system or the COMOD® system.

Particle

Eye drops in the form of solutions must be free of particles when visually inspected.

Eye drops in the form of suspensions must be easy to disperse and the dispersion must remain stable long enough to ensure that the dose is accurately withdrawn. Suspension eye drops must comply with the particle size test according to the European Pharmacopoeia. The test is carried out microscopically : a suspension corresponding to 10 µg of solid active substance may contain a maximum of 20 particles larger than 25 µm, of which a maximum of two particles larger than 50 µm and no particles larger than 90 µm. Suspensions are a form of administration for poorly soluble substances (e.g. glucocorticoids ).

Disadvantages of ophthalmic therapy

The conjunctival sac has only a small absorption capacity. During or after the application, the medicinal substance can be (partially) washed out, caused by a mechanical stimulus triggered by blinking the eye (also referred to as volume stimulus) or by increased tearfulness triggered by the irritant properties of the preparation. Slow or inadequate penetration of the active ingredient into the cornea can impair the effectiveness in certain areas of application. As the lacrimal system is connected to the nasal mucosa, systemic absorption cannot be ruled out.

Optimizing ophthalmic therapy

Some biopharmaceutical approaches aim to minimize drug loss and to increase the contact time of the preparation with the eye. Micro-drop devices allow z. B. the application of the drug dose in smaller volumes, whereby the volume stimulus is reduced or avoided. To extend the contact time, viscosity-increasing substances such as cellulose derivatives ( hypromellose , methyl cellulose ), hyaluronic acid , cellulose acetate phthalate or poloxamers can be used.

See also

• Pharmaceutical technology

Individual evidence

1. ^ ^{A b c} Alfred Fahr (ed.): Voigt Pharmazeutische Technologie . 12th edition. Deutscher Apotheker Verlag, Chapter 22 "Eye Medicines".
2. ↑ Jens Werner, Jessica Cordes, Christian Enders: Application of eye drops and eye ointments - step by step . In: Clinical monthly sheets for ophthalmology . tape 234 , no. 10 , October 2017, ISSN  0023-2165 , p. 1215-1217 , doi : 10.1055 / s-0043-118758 .
3. ↑ ^{a b c} Bauer, Frömmling, Führer: Textbook of Pharmaceutical Technology . 6th edition. Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart.
4. ↑ ^{a b c d e f} Deutscher Apothekerverlag (ed.): European Pharmacopoeia, 8th edition, basic work . 1163 “Preparations for use on the eye”.
5. ↑ ^{a b} Drug Dosing Systems in Ophthalmology. (PDF) Retrieved January 23, 2017 . 
6. ↑ Glaucoma, eye prescriptions . In: Deutsche Apotheker Zeitung . No. 32 . Deutscher Apotheker Verlag, August 6, 15.

Web links

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