[Triamcinolone acetonide without solvents]. / Acetónido de triamcinolona sin conservantes.

OBJECTIVE: The purification of commercially prepared triamcinolone acetonide is important in order to avoid the potential toxic side-effects of the solvent benzyl alcohol. We present a new technique for preparation of pure triamcinolone acetonide by dissolving the powder in sterile distilled water with no additional solvents. As the triamcinolone powder is relatively insoluble in water, we describe the sterile method used for the preparation and control of this suspension. MATERIALS AND METHODS: The triamcinolone acetonide is prepared in our hospital pharmacy, under optimum sterile conditions, and then packaged in a primary vial, sealed and sterilized in an autoclave at 121°C. This vial contains an individual dose of 4mg/0.1ml. RESULTS: A final dose for an intravitreal administration of 3.77mg/0.1ml triamcinolone acetonide was obtained using high pressure liquid chromatography (HPLC). The chemical, physical and microbiological stability allows the solution to be kept at a temperature of 2-8°C for 6 months. CONCLUSIONS: A rapid method is presented for preparing triamcinolone acetonide in pure state without preservatives in a concentration near the standard dose and under optimum sterile conditions.

Influence of different purification techniques on triamcinolone yield and particle size spectrum.

BACKGROUND: To systematically investigate the common purification techniques for commercially available triamcinolone acetonide preparations and the influence of different filter parameters on final yield, reproducibility and particle size spectrum. METHODS: Two non-filter techniques using either sedimentation or centrifugation, and two different filter techniques were tested. Filters with different characteristics were investigated with the pore size ranging from 0.1 to 5.0 microm, and the filter diameter ranging from 4 to 30 mm. Only sterile standard syringe filters with low adsorptive characteristics (hydrophilic cellulose filter membranes) for pharmaceutical use were employed. For quantification, triamcinolone acetonide was dissolved in 60% methanol and measured spectrophotometrically at 239 nm. The crystal size spectrum was determined using a particle size analyzer that combines electronic pulse area analysis and resistance measurement. RESULTS: Depending on the purification technique used the resulting triamcinolone doses differed significantly. While the centrifugation method achieved purification without relevant loss, the sedimentation method yielded only 28.7% compared to the original commercial suspension, and in addition, the predictability was low (range 8.1-17.2 mg). With filter techniques high and consistent doses with a good reproducibility were achieved, but results were highly dependent on the filter characteristics. The final triamcinolone amount inversely correlated with the filter diameter due to a uniform loss of crystalline particles. In contrast, enlarging the pore size caused a substantial shift in the particle size spectrum due to a selective loss of small crystalline particles. CONCLUSIONS: The most common purification techniques vary notably in regard to final triamcinolone doses, reproducibility and particle size spectrum. The appropriate choice of the filter parameters seems to be more important than assumed, as pore size and filter diameter substantially influence both the final TA doses and the particle size of the TA crystals.

Examination of purification methods and development of intravitreal injection of triamcinolone acetonide.

PURPOSE: Intravitreal injection of triamcinolone acetonide (TA) is used in ophthalmic treatment, but the reliability of commercially available TA preparations has still not been established. We evaluated two previously reported purification methods, and developed a more reliable TA injection which can be prepared in a hospital pharmacy. METHODS: We tested the two methods previously reported for purifying commercial TA preparations, the sedimentation and the filtration and backflushing methods. We developed a new TA injection made of pure TA suspended in 0.5% sodium hyaluronate. We measured the TA content in each preparation by high-performance liquid chromatography to evaluate the three methods. RESULTS: In the sedimentation purification method, the TA content of a nominal 4-mg preparation varied from 1.43 to 7.37 mg, and the average recovery rate was 91.6%. In the filtration and backflushing method, TA content was 0.10-10.33 mg and recovery was 59.5%. In the TA injection we developed, the mean TA content was 102.5% (SD, 0.24; CV, 2.9%). The stability of this preparation was 99% after sterilization, and 97% after 3 months of storage. CONCLUSIONS: The results of our investigation showed that the purification methods used for commercial preparations are simple and easy but not precise enough for an intravitreal injection. In contrast, the TA injection prepared by our method is reliable, stable, and safe enough for clinical use.

Comparison of different techniques for purification of triamcinolone acetonide suspension for intravitreal use.

BACKGROUND: Intravitreal triamcinolone has increasingly been used for the treatment of oedematous and neovascular diseases and purification of triamcinolone suspension may be important in order to avoid the potential toxic effects of the vehicle. The aim was to evaluate different techniques used to reduce the solvent agent benzyl alcohol (9.9 mg/ml) from a commercially prepared triamcinolone acetonide suspension. METHODS: Different techniques were used to reduce the solvent agent benzyl alcohol: filter techniques using 0.22 mum or 5 mum pore size, and non-filter techniques using sedimentation or centrifugation. Quantification of triamcinolone acetonide and benzyl alcohol was performed by high pressure liquid chromatography (HPLC). RESULTS: Benzyl alcohol concentration was decreased significantly in all the techniques used compared with the original commercial suspension (p<0.05), with no significant differences among them. The reduction was approximately one tenth of its original concentration. However, triamcinolone acetonide concentration differed significantly depending on the method used. Centrifugation method showed no differences versus the original commercial solution; sedimentation technique reduced the expected dose only 25%; the filter technique using a 5 mum pore size membrane reduced the expected dose to one fourth, while the filter technique using a 0.22 mum pore size membrane reduced the expected dose to 45%. CONCLUSIONS: All the different techniques employed effectively reduced the concentration of benzyl alcohol. However, the final concentration of triamcinolone was much lower than expected using the filter techniques. The pore size membrane inversely influenced the final concentration, with part of the triamcinolone crystals probably being entrapped in the filter. Centrifugation is recommended as the best way of administering the drug.

A simple and rapid method for purification of triamcinolone acetonide suspension for intravitreal injection.

Purification of triamcinolone acetonide suspension is important to avoid the potential toxic effects of the vehicle. The aim of this article is to describe a simple and rapid technique to remove the vehicle, instead of the long procedure described in the literature. Triamcinolone acetonide suspension was sedimented by density gradient centrifugation. In a few minutes, this new technique yielded a clear supernatant that was easily replaced by a nontoxic sterile solution. More prolonged procedures may not be convenient for unplanned treatments and may also contribute to a greater chance for contamination of the triamcinolone acetonide suspension.

Isolating triamcinolone acetonide particles for intravitreal use with a porous membrane filter.

PURPOSE: To report a new, simple, rapid method to isolate triamcinolone acetonide particles and to remove additives from its commercially available suspension (Kenacort-A) for intravitreal use. METHODS: The contents of a Kenacort-A vial (40 mg triamcinolone acetonide suspended in 1.0 mL vehicle) were loaded into a syringe and passed through a porous membrane filter with 0.45-microm pores. The filter was then backflushed with distilled water to yield a vehicle-poor suspension of triamcinolone acetonide in the initial syringe. This filtration and backflush procedure was repeated four times, and each waste filtrate was subjected to high-performance liquid chromatography to identify benzyl alcohol, a preservative in the vehicle. Gel permeation chromatography was also used to determine the degree to which carboxymethylcellulose, one of the two suspending agents in the vehicle, permeated the membrane filter. Although 7.5 mg/mL high-viscosity carboxymethylcellulose hardly passed through the 0.45-microm pore filter, it passed through the 5.0-microm pore filter easily. Therefore, a 5.0-microm pore filter was used in this study. RESULTS: By using a 0.45-microm porous membrane filter, 99.7% of the benzyl alcohol can be eliminated. By using a 5.0-microm porous membrane filter, but not by using a 0.45-microm porous membrane filter, 88.1% of the high-viscosity carboxymethylcellulose can be eliminated. CONCLUSIONS: The filtration and backflush procedure using the 5.0-microm porous membrane filters is useful during vitrectomy to reduce the preparation time of triamcinolone acetonide suspension. Also, this method of reducing additives may be more helpful when using triamcinolone as a therapeutic agent for intravitreal depot use, because there is no washout effect when it is used in this manner.