Administration, drugs ophthalmic

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. 

Topical application is the most common route of administration for ophthalmic drugs. Advantages include convenience, simplicity, noninvasive nature, and the ability of the patient to self-administer. Because of blood and aqueous losses of drug, topical medications typically do not penetrate in useful concentrations to posterior ocular structures and therefore are of no therapeutic benefit for diseases of the retina, optic nerve, and other posterior segment structures. 

Due to the accessibility of the eye surface, topical administration of ophthalmic medications is the most common method for treating conditions affecting the exterior eye surface. However, the unique anatomy and physiology of the eye renders it difficult to achieve an effective drug concentration at the target site. Therefore, efficient delivery of a drug past the protective ocular barriers accompanied with minimization of its systemic side effects remains a major challenge. 

One of the main problems encountered in ophthalmic drug delivery is the rapid and extensive elimination of conventional eye drops from the eye. Only a small amount (1-6 %) actually penetrates the cornea and reaches the intra ocular tissues [100]. The administration of ophthalmic drugs in hydrogels has been shown to increase the contact time of the drugs with cornea, thereby increasing ocular bioavailability. 

The incidence of adverse reactions associated with the ophthalmic drags is usually small. Because small amounts of the ophthalmic preparation may be absorbed systemically, some of the adverse effects associated with systemic administration of the particular drug may be observed. Some ophthalmic preparations produce momentary stinging or burning on instillation. 

Co-administration of ofloxacin and chitosan in eyedrops increased the bioavailabUity of the antibiotic [290]. Trimethyl chitosan was more effective because of its solubility (plain chitosan precipitates at the pH of the tear fluid). On the other hand, N-carboxymethyl chitosan did not enhance the corneal permeability nevertheless it mediated zero-order ofloxacin absorption, leading to a time-constant effective antibiotic concentration [291]. Also W,0-carboxymethyl chitosan is suitable as an excipient in ophthalmic formulations to improve the retention and the bioavailability of drugs such as pilocarpine, timolol maleate, neomycin sulfate, and ephedrine. Most of the drugs are sensitive to pH, and the composition should have an acidic pH, to enhance stability of the drug. The delivery should be made through an anion exchange resin that adjusts the pH at around 7 [292]. Chitosan solutions do not lend themselves to thermal sterilization. A chitosan suspension, however. 

Counsel patients about glaucoma, drug therapy options, ophthalmic administration techniques, and the importance of adherence to the prescribed regimen. 

Develop a patient-specific care plan for this patient. Be sure to address the patient s drug-related needs, goals of therapy, risks and benefits of potential therapies, and plan for follow-up of therapy. List the monitoring parameters for effectiveness and safety for the chosen therapy. Explain how you would counsel the patient on the chosen therapy, including the administration of an ophthalmic preparation. 

The significance of the barrier function of membranes has been the topic of considerable research. The blood-brain barrier and the blood-retinal barrier are well understood, and the microscopic structures imparting and controlling barrier properties have been quite thoroughly investigated and the science reviewed [15, 154-155], The structures and functions of ocular membranes specific to transport associated with ophthalmic drug administration also have been topics of extensive research [15, 157-158],... 

The US Food and Drug Administration (FDA) allows PVA for use as an indirect food additive in products which are in contact with food [11], For example, under 21 CFR 73.1, PVA is approved as a diluent in color additive mixtures for coloring shell eggs and under 21 CFR 349.12, PVA is approved as an ophthalmic demulcent at 0.1-4.0 %. 

The provision of optimal drug action from topical administration sites (such as ointments, creams, transdermal patches, ophthalmic, ear, and nasal preparations)... 

General considerations in topical ophthalmic drug therapy Proper administration is essential to optimal therapeutic response. In many instances, health professionals may be too casual when instructing patients on proper use of ophthalmics. The administration technique used often determines drug safety and efficacy. 

Table 3 indicates the preclinical safety studies for CAPTISOL (25) conducted as of 2005. The strategic safety plan for CAPTISOL was designed based on the guidelines discussed in the 1990s by the International Pharmaceutical Excipients Council which resulted in the May 2005 issuance of the FDA Guidance (26) Nonclinical Studies for the Safety Evaluation of Pharmaceutical Excipients. These studies and others in the CAPTISOL Drug Master File have delineated the safety of CAPTISOL (SBE7-P-CD) for parenteral, ophthalmic, oral, nasal, and inhalation administration. 

A 34-year-old woman with primary open-angle glaucoma began topical application of travoprost ophthalmic solution (0.004%, 1 drop/day) and 30 minutes later developed abdominal cramp that lasted for 2 hours. The same symptoms appeared on 3 days after drug administration. The pain disappeared after travoprost withdrawal. 

Ophthalmic, transmucosal, and transdermal products will be the most sensitive to the strength of binding. These routes of administration experience minimal dilution. However, this may not be a signiLcant concern because the drug typically can also be displaced from the CD cavity at the delivery site by competing lipophiles at the delivery site, such as triglycerides, cholesterol, bile salts, and other hydrophobic compounds, which are often in much higher concentrations (Thompson, 1997). 

After topical administration of an ophthalmic drug solution, the drug has to cross a succession of anatomical barriers before reaching the systemic circulation. These barriers (as shown in Figure 25.1) can be commonly classified as precorneal and corneal barriers [3]. 

The most common drug delivery method for treating ocular disorders is topical administration, due to its convenience and safety. However, the anterior segment of the eye also has various protective mechanisms for maintaining visual functions. After instillation of an ophthalmic drug, most of it is rapidly eliminated from the precorneal area due to drainage by the nasolacrimal duct and dilution by the tear turnover (approximately 1 pL/min) [17,18]. In addition, there is a finite limit to the size of the dose that can be applied and tolerated by... 

A 0.1% ophthalmic preparation is recommended for prevention of postoperative ophthalmic inflammation and can be used after intraocular lens implantation and strabismus surgery. A topical gel containing 3% diclofenac is effective for solar keratoses. Diclofenac in rectal suppository form can be considered a drug of choice for preemptive analgesia and postoperative nausea. In Europe, diclofenac is also available as an oral mouthwash and for intramuscular administration. 

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