Vincent Baeyens

Chemical and physical parameters of tears relevant for the design of ocular drug delivery formulations.

This paper provides a summary of the most important chemical and physical parameters of tears that can help the formulator in the development of new ocular formulations and in the conception of innovative ophthalmic delivery approaches. For each physiological parameter, the relevance in ocular drug delivery is discussed in detail and the analytical tools that are used for the determination of these parameters are described and summarized. The aim of this review is also to give a description of the main analytical techniques available in ophthalmology that can be used for pharmacokinetic studies of active compounds. The importance of tear sampling techniques used in the determination of the parameters is also discussed.

A poly(ortho ester) designed for combined ocular delivery of dexamethasone sodium phosphate and 5-fluorouracil: subconjunctival tolerance and in vitro release

A viscous hydrophobic poly(ortho ester) (POE) has been developed as a biocompatible, biodegradable sustained release system for selected cases of glaucoma filtering surgery. Dexamethasone and 5-fluorouracil (5-FU) are frequently administered together post-operatively, for their anti-fibroblastic and anti-inflammatory properties, respectively. A combined sustained release of both drugs could be advantageously used. Drug release kinetics were studied using specially designed thermostated cells. Subconjunctival tolerance was evaluated on New Zealand albino rabbits by clinical evaluation. Due to its basicity, the addition of dexamethasone sodium phosphate (DEX-P) stabilized the polymer and prolonged 5-FU in vitro release from 2 to 4 days. Both therapeutic agents were released concomitantly, according to a linear profile. The presence of 5-FU only slightly affected the overall subconjunctival tolerance of POE in rabbits, whereas the addition of DEX-P markedly improved POE tolerance by reducing the hyperemia of the conjunctiva to a minimal grade.

Clinical evaluation of bioadhesive ophthalmic drug inserts (BODI®) for the treatment of external ocular infections in dogs

In the case of external ocular diseases such as conjunctivitis, keratoconjunctivitis sicca (KCS) and superficial corneal ulcers, topical administration of eyedrops containing an antibacterial agent is often prescribed. Numerous daily instillations of eyedrops over several days are required for successful treatment, often leading to bad compliance. In addition, the reflex lachrymation following instillation promotes rapid elimination of the drug from the corneal surface. To overcome the disadvantage of repeated instillations, a soluble bioadhesive ophthalmic drug insert (BODI) to be placed in the lower cul de sac of the eye was developed. The clinical efficacy, after deposition of one insert and a classical eyedrop treatment (Tiacil), Virbac Laboratories), was investigated in dogs presenting conjunctivitis, superficial corneal ulcer or keratoconjunctivitis sicca (KCS). Similar total clinical recovery results were obtained after 3 and 7 days for both treatments. BODI can therefore advantageously be prescribed for the treatment of external ophthalmic diseases, by reducing the treatment to a single application and therefore improving compliance compared to classical eyedrop treatment.

Determination of dexamethasone in tears by capillary electrophoresis

A selective capillary zone electrophoresis (CZE) microassay was developed for the simultaneous determination of dexamethasone phosphate and its major metabolite, dexamethasone, in tears. The calibration was carried out in the biological matrix with indoprofen as an internal standard which allowed the separation of dexamethasone phosphate and dexamethasone from the tear constituents. The limits of detection and quantification of the assay were 0.5 and 2.0 microg ml(-1), respectively. This quantification method is essential for the in vivo determination of dexamethasone concentration-time profiles in tears after application of the antiinflammatory drug.

Optimized release of dexamethasone and gentamicin from a soluble ocular insert for the treatment of external ophthalmic infections

In the case of external ophthalmic infections, repeated instillations of antibiotics are required to reach therapeutic level, above the minimal inhibitory concentration (MIC). An additional administration of a corticosteroid is often needed, in order to limit the precorneal damages caused by the infection. However, repeated administration of a corticosteroid can increase intraocular pressure and thus lead to glaucoma. To overcome the disadvantages of separated and repeated instillations of two products and to avoid the side effects of dexamethasone, a soluble insert containing gentamicin sulfate and dexamethasone phosphate was developed. The new system ensures the concomitant release of the two drugs during the first 10 h of treatment, followed by an adequate concentration of gentamicin sulfate, above the MIC of 4.0 microgram ml-1, during 50 h, due to a combination of gentamicin sulfate with cellulose acetate phthalate, which reduces the solubility of gentamicin.

Ocular drug delivery in veterinary medicine

This paper provides a comprehensive overview of the various approaches currently used in the development of ocular drug delivery systems for the treatment of ocular diseases in animals. It is obvious from the literature that most of the products that are currently available are derived from human medicine without consideration given to the differences which exist between the anatomy and physiology of the eye of various animal species which ultimately affect product design and performance. As a result, many of the products for animal use seem in many circumstances inappropriate for animal care. The article deals with some aspects of eye anatomy and physiology of different animals, and then provides an overview of the most commonly encountered pathologies. The paper then discusses the currently available drug products and finally reviews new delivery concepts. Several hundred references are included in the paper and provide access to further information on the subject.