Formulations ophthalmic

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. 

Figure 14 SEC chromatogram of carboxymethylcellulose in an ophthalmic formulation. The horizontal axis is elution time in minutes and the vertical axis is DRI response in arbitrary units.

Current guidelines for toxicity evaluation of ophthalmic formulations involve both single and multiple applications, dependent on the proposed clinical use [39]. The multiple applications may extend over a 9-month period and incorporate evaluations of ocular irritation and toxicity, systemic toxicity, and determinations of systemic exposure (toxicokinetics). In many cases the systemic exposure from an ocular route is less than by parenteral administration, information that will assist in determining whether additional studies may be needed to establish systemic safety of the ophthalmic preparation. U.S. and international guidance documents are available [71,72], and regulations and tests have been summarized for ophthalmic preparations [39,73,74],... 

This preservative is also comparatively new to ophthalmic formulations and has been used as a disinfectant in contact lens solutions. Polyaminopropyl biguanide (polyhexamethyl biguanide) also is a polymeric compound that has a low toxicity potential at the concentrations generally used in these solutions [141, 149, 150]. 

Although usually considered to be inactive ingredients in ophthalmic formulations added because they impart viscosity, many of these polymers function as ocular lubricants. They are marketed as the active ingredients in OTC ocular lubricants used to provide relief from dry eye conditions. The regulatory requirements for these OTC products are found in the FDA Code of Federal Regulations (21CFR349.12), and their formulations are presented in the Twelfth Edition of the APhA Handbook of Nonprescription Drugs. 

The pH dependence of dorzolamide solubility was also determined between pH 4.0 and 7.0, using acetate, citrate, and phosphate buffer solutions to set the desired pH. These data are collected in Table 2 (also plotted in Figure 4), and show a maximum solubility of approximately 40 mg/mL at pH 5.6. The equilibrium solubility decreases to approximately 13 mg/mL at pH 6 and 4 mg/mL at pH 7.0. These data indicate that in order to have a stable 2% solution for an ophthalmic formulation, the solution pH should be maintained below 5.8. At pH values exceeding 5.8, precipitation of the free base could occur. 

Flurbiprofen is also available in a topical ophthalmic formulation for inhibition of intraoperative miosis. Flurbiprofen intravenously is effective for perioperative analgesia in minor ear, neck, and nose surgery and in lozenge form for sore throat. 

The efficacy of flurbiprofen at dosages of 200-400 mg/d is comparable to that of aspirin and other NSAIDs in clinical trials for patients with rheumatoid arthritis, ankylosing spondylitis, gout, and osteoarthritis. It is also available in a topical ophthalmic formulation for inhibition of intraoperative miosis. Flurbiprofen intravenously has been found to be effective for perioperative analgesia in minor ear, neck, and nose surgery and in lozenge form for sore throat. 

Presoaked lenses are considered a more efficient and reliable delivery system. However, the soaking of lenses in ophthalmic formulations to incorporate the drag into the lens may cause toxicity to corneal epithelium because preservatives, such as benzalkonium chloride, have a great affinity for the hydrophilic contact lens material and are concentrated in the contact lens. Contact lens for sensitive wearers may also cause foreign-body sensation, blurring and decreased oxygen tension on the corneal surface resulting from occlusion by contact lens. 

Conventional eye drops currently account for more than 90% of the marketed ophthalmic formulations [1], However, after instillation of an eye drop, typically less than 5% of the applied drug penetrates the cornea and reaches the intraocular... 

Ocular inserts probably represent one of the oldest ophthalmic formulation approaches. In 1948 the British Pharmacopoeia described an atropine-in-gelatin wafer and ever since then numerous systems have been developed applying various polymers and different release principals. However, the difficulty of insertion by the patient, foreign-body sensation, and inadvertent loss of inserts from the eye make these systems less popular, especially among the elderly. Furthermore, the high cost involved in manufacture prevented the insert market from taking off [197],... 

Nijhawan, R., and Agarwal, S. P. (2003), Development of an ophthalmic formulation containing ciprofloxacin-hydroxypropyl-P-cyclodextrin complex, Boll. Chim. Farm,., 142(5), 214-219. 

Dipivefrin Ophthalmic formulations HPLC for cyclizine) No treatment Cm, Bondapak... 

---