Packaging ophthalmic formulations

PVA is biocompatible, easy to process, hydrophilic, and has good physical and chemical properties. PVA exhibits excellent barrier properties against oils and fats, aromas, and small gas molecules [48]. In addition to its biocompatibility, PVA is also an environment-friendly polymer as it can be biodegraded into CO2 and water by the action of microorganisms. PVA is widely used in pharmaceutical and ophthalmic formulations, food, adhesive, textile, paper and packaging industries. PVA is used as an industrial polymer maiidy because of its low environmental impact due to its aqueous solubUily, high chemical resistance, and biodegradability (Baker et al. 2012). 

This aromatic alcohol has been an effective preservative and still is used in several ophthalmic products. Over the years it has proved to be a relatively safe preservative for ophthalmic products [138] and has produced minimal effects in various tests [99,136,139]. In addition to its relatively slower rate of activity, it imposes a number of limitations on the formulation and packaging. It possesses adequate stability when stored at room temperature in an acidic solution, usually about pH 5 or below. If autoclaved for 20-30 minutes at a pH of 5, it will decompose about 30%. The hydrolytic decomposition of chlorobutanol produces hydrochloric acid (HC1), resulting in a decreasing pH as a function of time. As a result, the hydrolysis rate also decreases. Chlorobutanol is generally used at a concentration of 0.5%. Its maximum water solubility is only about 0.7% at room temperature, which may be lowered by active or excipients, and is slow to dissolve. Heat can be used to increase dissolution rate but will also cause some decomposition and loss from sublimation. Concentrations as low as 0.125% have shown antimicrobial activity under the proper conditions. 

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... 

Due to the safety and regulatory concerns raised by preservatives used in ophthalmic products, there have been efforts to develop new eye-drop packaging systems which can remove the preservative from the formulation during administration. BKC is the most common preservative used in commercial eye-drops, and yet there are reports of side-effects such as allergic reactions, irritation, decreased lacrimation and damage to the corneal endothelium caused by its multiple use in eye products (Fraunfelder and Meyer 1989). Also, BKC can... 

For solid products the risk of migration is low and therefore interaction studies are not required over and above the normal stability test results. For semi-solid products it is necessary to look particularly at the migration of additives, vapour permeation and the effects of the product on the physical parameters of the pack. For liquid products the migration potential for the specific formulation is required, and the determination of active ingredient content under simulated use, along with extractives data is required for parenteral and ophthalmic products. Moisture permeation is important, particularly for solid products packaged in blister packs. 

It is preferable to formulate ophthalmic nanoemulsions devoid of preservative agents and fill them in sterile single dose packaging units to prevent potential contamination due to repeated use of multi-dose packaging. ... 

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