Review
Vesicular systems in ocular drug delivery: an overview

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Abstract

The main aim of pharmacotherapeutics is the attainment of effective drug concentration at the intended site of action for a sufficient period of time to elicit a response. Poor bioavailability of drugs from ocular dosage form is mainly due to the tear production, non-productive absorption, transient residence time, and impermeability of corneal epithelium. Though the topical and localized application are still an acceptable and preferred way to achieve therapeutic level of drugs used to treat ocular disorders but the primitive ophthalmic solution, suspension, and ointment dosage form are no longer sufficient to combat various ocular diseases. This article reviews the constraints with conventional ocular therapy and explores various novel approaches, in general, to improve ocular bioavailability of the drugs, advantages of vesicular approach over these and the future challenges to render the vesicular system more effective.

Introduction

Drug delivery in ocular therapeutics is a challenging problem and is a subject of interest to scientists working in the multi-disciplinary areas pertaining to the eye, including chemical, biochemical, pharmaceutical, medical, clinical, and toxicological sciences. Recently, increased attention has been focussed on two main objectives:

  • (A)

    To find or tailor make newer, effective, and safe drug molecules for various ocular conditions and diseases that are poorly controlled.

  • (B)

    To improve existing ocular dosage forms and exploit newer delivery systems for improving the ocular bioavailability of existing molecules.

Current trends in ocular therapeutics and drug delivery suggest that the existing dosage forms will be replaced by novel drug delivery systems that offer improved biopharmaceutical properties with the capability to deliver therapeutic agents more precisely to targeted receptors in the eye in a predictable manner (Reddy and Ganesan, 1996).

Drugs are commonly applied to the eye for a localized action on the surface or in the interior of the eye (Davies, 2000). A major problem in ocular therapeutics is the attainment of an optimal drug concentration at the site of action. Poor bioavailability of drugs from ocular dosage form is mainly due to the precorneal loss factors which include tear dynamics, non-productive absorption, transient residence time in the cul-de-sac, and the relative impermeability of the corneal epithelial membrane (Shell and Baker, 1974, Le Bourlais et al., 1998, Kaur and Kanwar, 2002). Due to these physiological and anatomical constraints, only a small fraction of the administered drug, effectively 1% or even less of the instilled dose is ocularly absorbed (Shell, 1984, Burstein and Anderson, 1985). This forces the clinician to recommend a frequent dosing at an extremely high concentration and pulse type dosing results in several side effects of ophthalmic products. In order to overcome the problems of conventional ocular therapy, such as short residence time, drug drainage, and frequent instillation; newer delivery systems are being explored, in general, to improve the ocular bioavailability of the drug.

Various approaches, like viscosity enhancement, use of mucoadhesive, particulate drug delivery, vesicular drug delivery, prodrugs, and other controlled systems, like ocuserts, are being explored (Sirbat et al., 2000, Kaur and Kanwar, 2002, Kaur and Smitha, 2002, Bourlais et al., 1998). In this review, the constraints with conventional topical dosage forms, possible newer approaches, and the need to develop vesicular delivery systems, shall be discussed.

Section snippets

Conventional ocular drug delivery constraints

For the ailments of the eye, topical administration is usually preferred over systemic administration so as to avoid systemic toxicity, for rapid onset of action, and for decreasing the required dose.

Though topical administration offers many advantages to treat disorders of anterior structures of the eye, it suffers from a serious disadvantage of poor bioavailability due to several biological factors (Fig. 1), which exist to protect the eye and consequently limit the entry of ocular drugs. The

Formulation approaches to improve ocular bioavailability

Various approaches that have been attempted to increase the bioavailability and the duration of therapeutic action of ocular drugs can be divided into two categories. The first is based on use of the drug delivery systems, which provide the controlled and continuous delivery of ophthalmic drugs. The second involves, maximizing corneal drug absorption and minimizing precorneal drug loss.

The typical pulse entry type drug release behavior observed with ocular aqueous solutions (eye drops),

Vesicular drug delivery systems

Vesicular systems not only help in providing prolonged and controlled action at the corneal surface but also help in providing controlled ocular delivery by preventing the metabolism of the drug from the enzymes present at the tear/corneal epithelial surface. Moreover, vesicles offer a promising avenue to fulfill the need for an ophthalmic drug delivery system that has the convenience of a drop, but will localize and maintain drug activity at its site of action. The penetration of drug

Further developments to render the vesicular systems more effective

Since, vesicular systems offer a great deal of advantages over the conventional systems, various pharmaceutical approaches can be tried to render their final formulation more effective. The best way to achieve this would be to enhance the precorneal retention. One such approach is combinatorial drug delivery. Combinatorial drug delivery systems are a new trend in ophthalmic research, with the great potential of combining the advantages of various systems and overcoming their limitations.

  • •

    Use of

Conclusion

Although eye drops represent 90% of all ophthalmic dosage forms, there is a significant effort directed towards new drug delivery systems for ophthalmic administration. It is the consensus of most clinicians that the patient prefers a solution form of ocular drug delivery system provided that extended duration can be accomplished by these forms. Most of the formulation efforts aim at maximizing ocular drug absorption through prolongation of the drug residence time in the cornea and conjunctival

Acknowledgements

The authors wish to acknowledge the financial support provided by Council of Scientific and Industrial Research (CSIR), New Delhi, India.

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