Novel method of compounding preservative-free triamcinolone simple, reproducible

A new direct suspending technique appears simple and reproducible for producing preservative-free triamcinolone acetonide suspensions suitable for intravitreal injection, according to a study by researchers in Switzerland and Austria.

"The simple method of direct suspending has a low risk for microbiologic contamination and is practical for batch production," the study authors said.

Christian Pruente, MD, and colleagues evaluated three different methods of compounding triamcinolone suspensions. The methods included the membrane-filter method, centrifugation and a direct suspending method developed by the authors' research group, according to the study.

"Our aim was to find a technique to compound a completely preservative-free [triamcinolone acetonide] suspension, adapted to the intraocular physiology, and with consistent quality," they said.

The direct suspending method involves mixing micronized triamcinolone with saline in a 250 mL injection vial containing a magnetic stir bar. The triamcinolone-saline mixture is then autoclaved for 20 minutes and mixed with a hyaluronic acid product under aseptic conditions to regulate viscosity, according to the study.

For each compounding method, investigators examined the resulting triamcinolone content, particle size, sterility and bacterial endotoxin content. They also evaluated each suspension's stability at room temperature and at 40° C, according to the study.

The direct suspending method produced uniform doses between 3.8 mg and 4 mg for each 0.1 mL injection vial that fulfilled all quality requirements, including a shelf life of 2 years, the authors reported.

The centrifugation method also yielded uniform doses, with uniformities between 3.7 mg and 4.5 mg. However, some benzyl alcohol concentrations were detectable, and some particles were as large as 100 µm, "which does not comply with the requirements of [British Pharmacopoeia 2007]," the authors said.

Investigators deemed the membrane filter method as not capable of producing triamcinolone suspensions adequate for batch production.

"The membrane-filter method is an ad hoc production technique only suitable for sporadic preparation, but not to satisfy a great demand of [triamcinolone acetonide] suspensions. Standardization of the multiple-step procedure is not possible," they said.

The study is published in the January issue of Journal of Ocular Pharmacology and Therapeutics.