Ophthalmic drug sterile

It is quite rare that the composition or the packaging of an ophthalmic pharmaceutical will lend itself to terminal sterilization, the simplest form of manufacture of sterile products. Only a few ophthalmic drugs formulated in simple aqueous vehicles are stable to normal autoclaving temperatures and times (121°C for 20-30 min). Such heat-resistant drugs may be packaged in glass or other heat-de-formation-resistant packaging and thus can be sterilized in this manner. The convenience of plastic... 

Although ophthalmic drug products can be considered topical products, they have been grouped here with inject-ables because they are required to be sterile (21 CFR 200.50(a)(2)) and the descriptive, suitability, and quality control information is typically the same as that for an injectable drug product. Because ophthalmic drug products are applied to the eye, compatibility and safety should also address the container closure system s potential to form substances which irritate the eye or introduce particulate matter into the product (see USP <771> Ophthalmic Ointments). 

Although ophthalmic drug products can be considered topical products, they have been grouped here with injectables because they are required to be sterile and the descriptive, suitability, and quality control information is typically the same as that for an injectable drug product. 

Topical dosage forms such as unpressurized sprays, lotions, ointments, solutions, and suspensions may be considered for marketing in glass bottles with appropriate dispenser. Some topical drug products, especially ophthalmic, are sterile or may be subject to microbial limits. In these cases, packaging material and handling should be done as those for injectables. 

It is noteworthy that, at least presently, sterilization is not required for all drugs. It depends on the type of administration. Hence, it concerns mostly ophthalmic preparations, sterile topical products and injectable solutions, including intramuscular, intravenous and sub-cutaneous ways. 

The following conclusions can be offered at the end of this brief review. Emulsion systems, particularly, mtcroemulsions, seem to be developing rapidly toward commercial applications and possibly will become the vehicles of choice for lipid-soluble ophthalmic drugs. Traditional suspensions, used for ocular administration of drugs both water- and lipid-insoluble, after some initial uncertainties have apparently reached a stale of technical perfection. However, both emulsions and suspensions are not exempt of drawbacks and problems such as stability, sterilization, bioavailability. etc., which may limit their practical usefulness. 

A new field of radiation application is the radiation sterilization of drugs. The requirement for sterility of drugs depends on type of administration. It concerns mostly ophthalmic preparations, sterile topical products, and injectable solutions. In some cases, radiation sterilization appears to be an attractive alternative to other types of sterilization, e.g., heat sterilization. For drugs the usual requirement (six orders of magnitude decrease in the microorganism level) is achieved by applying an absorbed dose of 25 kGy. 

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. 

An erodible insert developed as a potential ocular drug-delivery system is marketed as a prescription drug for the lubricant properties of the polymer base. Lacrisert is a sterile ophthalmic insert used in the treatment of moderate to severe dry eye syndrome and is usually recommended for patients unable to obtain symptomatic relief with artificial tear solutions. The insert is composed of 5 mg of hydroxypropylcellulose in a rod-shaped form about 1.27 mm diameter by about 3.5 mm long. No preservative is used, since it is essentially anhydrous. The quite rigid cellulose rod is placed in the lower conjunctival sac and first imbibes water from the tears and after several hours forms a... 

Lee [73] studied the stability of miconazole on dry heating in vegetable oils. Miconazole was stable when subjected to dry heat (160 °C for 90 min) in either peanut or castor oil as determined by high performance liquid chromatography analysis. Thus, ophthalmic preparations of miconazole can be prepared in peanut or castor oil with dry heat sterilization without the loss of the drug due to degradation. The procedure also facilitates quick and easy dissolution of the drug in the oil base. 

Ophthalmic Dosage Forms. Ophthalmic preparations can be solutions, e.g. eye drops, eyewashes, ointments, or aqueous suspensions. They must be sterile and any suspended drug particles must be of a very fine particle size. Solutions must be particle free and isotonic with (cars. Thus, the osmotic pressure must equal that of normal saline (0.9% sodium chloride) solution. Hypotonic solutions are adjusted to be isotonic by addition of calculated amounts of tonicity adjusters, e.g., sodium chloride, boric add, or sodium nitrate. 

In conclusion, the approval of Restasis by the FDA is an important milestone in lipid emulsion research for ophthalmic application. This approval reflects the achievements of the last decade in terms of the availability of better ingredients, improved manufacturing processes, feasibility of sterilization, and better understanding of the optimization process. In all of the comparative studies done so far, positively charged SME achieved better ocular bioavailability regardless of the studied drug. Research efforts are underway to further explore the mechanism of interaction of positively charged SMEs with ocular tissues and to translate the results of this research into enhanced clinical performance. 

Ointments are semisolid preparations intended for topical application. They are used to provide protective and emollient effects on the skin or carry medicaments for treating certain topical ailments. They are also used to deliver drugs into eye, nose, vagina, and rectum. Ointments intended for ophthalmic purposes are required to be sterile. When applied to the eyes, they reside in the conjunctival sac for prolonged periods compared to solutions and suspensions and improve the fraction of drug absorbed across ocular tissues. Ophthalmic ointments are preferred for nighttime applications as they spread over the entire corneal and conjunctival surface and cause blurred vision. 

According to Davies [174], topical ophthalmic suspensions have a number of limitations compared to solutions. They need to be adequately shaken before use to ensure correct dosing, a process which can result in poor patient compliance. In addition, they need to be sterilized, which may cause physical instability of the formulation. Furthermore, the amount of drug required to achieve only a moderate increase in bioavailability is very high, rendering suspensions expensive in terms of their production costs [175],... 

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