Ocular Preparations: The Formulation Approach

Abstract

The main aim of pharmacotherapeutics is the attainment of an effective drug concentration at the intended site of action for a sufficient period of time to elicit the response. A major problem being faced in ocular therapeutics is the attainment of an optimal concentration at the site of action. Poor bioavailability of drugs from ocular dosage forms is mainly due to the tear production, non-productive absorption, transient residence time, and impermeability of corneal epithelium. This article reviews: (1) the barriers that decrease the bioavailability of an ophthalmic drug; (2) the objectives to be considered in producing optimal formulations; and (3) the approaches being used to improve the corneal penetration of a drug molecule and delay its elimination from the eye. The focus of this review is on the recent developments in topical ocular drug delivery systems, the rationale for their use, their drug release mechanism, and the characteristic advantages and limitations of each system. In addition, the review attempts to give various analytical procedures including the animal models and other models required for bioavailability and pharmacokinetic studies. The latter can aid in the design and predictive evaluation of newer delivery systems. The dosage forms are divided into the ones which affect the precorneal parameters, and those that provide a controlled and continuous delivery to the pre- and intraocular tissues. The systems discussed include: (a) the commonly used dosage forms such as gels, viscosity imparting agents, ointments, and aqueous suspensions; (b) the newer concept of penetration enhancers, phase transition systems, use of cyclodextrins to increase solubility of various drugs, vesicular systems, and chemical delivery systems such as the prodrugs; (c) the developed and under-development controlled/continuous drug delivery systems including ocular inserts, collagen shields, ocular films, disposable contact lenses, and other new ophthalmic drug delivery systems; and (d) the newer trends directed towards a combination of drug delivery technologies for improving the therapeutic response of a non-efficacious drug. The fruitful resolution of the above-mentioned technological suggestions can result in a superior dosage form for both topical and intraocular ophthalmic application.

Ocular delivery of natamycin based on monoolein/span 80/poloxamer 407 nanocarriers for the effectual treatment of fungal keratitis

“…Natamycin is BCS class II drug and due to its high molecular weight, corneal permeation is low. The conventional therapy for natamycin surfaces some notable drawbacks such as high dosing frequency, longer time period treatment cycles (4-6 weeks) and due to fast removal by nasopharyngeal drainage residence time at the ocular mucosa is short [3]. Extensive efforts have been directed towards the enhancement of ophthalmic drug bioavailability by exploring novel drug delivery strategies [3].…”

“…The conventional therapy for natamycin surfaces some notable drawbacks such as high dosing frequency, longer time period treatment cycles (4-6 weeks) and due to fast removal by nasopharyngeal drainage residence time at the ocular mucosa is short [3]. Extensive efforts have been directed towards the enhancement of ophthalmic drug bioavailability by exploring novel drug delivery strategies [3]. The delivery alternatives aim at improving both the precorneal residence time and in boosting the trans-corneal permeation of the drug [4,5].…”

Preparation and Evaluation of Thermosensitive Liposomal Hydrogel for Enhanced Transcorneal Permeation of Ofloxacin

“…The bioavailability of traditional ocular drug delivery systems, such as eye drops, is very poor (1); this is due to the fact that most of the instilled drug is lost within the first 15-30 s after instillation, and less than 5% of the applied drug penetrates the cornea and reaches intraocular tissues (2,3). Many efforts in ophthalmic drug delivery have been devoted not only to prolong the contact time of the vehicle at ocular surface but also slow down the elimination of the drug and increase its corneal penetration (4).…”

Recent Perspectives in Ocular Drug Delivery

“…This formulation exhibited excellent stability when compared to commercially available formulation. Though microemulsions have excellent advantages limitations in selection of surfactant/co-surfactant system and potential toxicity associated with higher concentrations of surfactant/co-surfactant often restricts its use (76). …”