Ocular dosage forms

The first stmeture encoimtered by an ocular dosage form is the precorneal tear film, consisting of three layers ... 

Typically less than 3% of topically applied drugs in ocular dosage forms—solutions. 

FIGURE 25.1 Factors affecting the poor bioavailability from ocular dosage forms. 

Tear production can be divided into basal, reflex, and emotional tearing [9]. Reflex tearing can be induced by many pharmaceutical/formulation factors, including the drug itself as well as pH and tonicity of the ocular dosage form. 

Ocular Inserts Solid ocular dosage forms such as films, erodible and nonerodible inserts, rods, and shields have been developed to overcome the typical pulse-entry-type drug release associated with conventional ocular dosage forms. This pulse entry... 

Albasini, M., and Ludwig, A. (1995), Evaluation of polysaccharides intended for ophthalmic use in ocular dosage forms, Farmaco, 50(Sept.), 633-642. 

Topical ocular application of controlled drug delivery systems is a relatively new science compared to earlier ocular dosage form, with roots beginning in the late 1960s to early 1970s. 

Pilocarpine is a drug commonly used in glaucoma therapy to relieve intraocular pressure (lOP), which is a cause of great discomfort to the patient. Piloplex is a sustained-release product based on an emulsion system of pilocarpine bound to a polymeric carrier [87,88]. Piloplex was shown to prolong a reduction in lOP as compared to standard pilocarpine hydrochloride drops. This is attributed to its bioadhesive properties, which keep the drug in the precorneal area longer than do conventional ocular dosage forms. 

In this chapter several aspects of ocular dosage forms are discussed with emphasis on eye drops, eye lotions and eye ointments prepared in pharmacies. Their formulation, method of preparation, packaging, storage and methods of administration are also discussed. 

The availability of medicines in ocular dosage forms is low due to the efficient barrier function of the cornea, lachrymation, tear turn over and drainage. Formulations should take into account these constraints. The vehicle and excipients selected should improve the permeation of the active substances in the eye or the residence in the conjunctival sac and consequently the therapeutic effects, but also minimise irritation. Tolerance of the preparation is of utmost importance. 

In as much as products for the diagnosis and treatment of ocular disease cover the spectrum of practically all dosage forms and, thus, require the same pharmaceutical sciences for their development, in this chapter we discuss the entire scope of considerations involved in the development of ophthalmic products, ranging from regulatory and compendial requirements, through physicochemical, safety, and efficacy considerations, to a discussion of types of dosage forms currently used by the medical practitioner. 

In-depth discussions of the anatomy of the eye and adnexa have been adequately covered elsewhere in the pharmaceutical literature [13-17] and in recent texts on ocular anatomy. Here a brief overview is presented of the critical anatomical features that influence the nature and administration of ophthalmic preparations. In this discussion, consideration will be given primarily to drugs applied topically, that is, onto the cornea or conjunctiva or into the palpebral fornices. Increasingly, drugs are being developed for administration by parenteral-type dosage forms subconjunctivally, into the anterior and posterior chambers, the vitreous chamber, Tenon s capsule, or by retrobulbar injection. 

The choice of a particular inactive ingredient and its concentration is based not only on physical and chemical compatibility, but also on biocompatibility with the sensitive and delicate ocular tissues. Because of the latter requirement, the use of inactive ingredients is greatly restricted in ophthalmic dosage forms. 

The Ocusert Pilo-20 and Pilo-40 Ocular Therapeutic System is an elliptical membrane that is soft and flexible and designed to be placed in the inferior cul-de-sac between the sclera and the eyelid and to release pilocarpine continuously at a steady rate for 7 days. The design of the dosage form is described by Alza in terms of an open-looped therapeutic system, having three major components (a) the drug, (b) a... 

Dosage Forms for Oral, Ocular, and Nasal Applications... 

Chloramphenicol also is widely used for the topical treatment of eye infections. It is a very effective agent because of its extremely broad spectrum of activity and its ability to penetrate ocular tissue. The availability of safer, less irritating instilled ophthalmic antibiotics and the increase in fatal aplastic anemia associated with the use of this dosage form suggest that this agent might best be withdrawn. 

Topical delivery systems are self-contained, discrete dosage forms that are designed to deliver drug via intact skin or body surface. There are three types of topical delivery systems transdermal, ocular, and intrauterine. 

Certain kinds of improvements are possible in almost every dosage form. Besides oral and injectable formulations, CD inclusion has been shown to improve bioavailability of compounds administered by other routes, including ocular, topical, nasal, and rectal routes (Uekama et al., 1994 Marttin et al., 1998 Bary et al., 2001 Loftsson and Masson, 2001 Rode et al., 2003). Some important applications particularly applicable for insoluble compounds are summarized below. 

Bochot, A., et al. 1998. Comparison of the ocular distribution of a model oligonucleotide after topical instillation in rabbits of conventional and new dosage forms. J Drug Target 6 309. 

Carbopol resins also have been used in controlled-release dosage forms. Especially, the resins Noven AA-1 USP and Carbopol 934P NF are being extensively developed in bioadhesive drug delivery systems for topical, bucal or nasal, ocular, and rectal applications (e.g., Fentanyl ). Noven CA-1 USP and CA-2 USP are used as oral laxative and antidiarrheal products in swallowable and chewable tablets. 

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