Physical and Chemical Compatibility of Extended-Release Triamcinolone Acetonide (TA-ER) with Common Local Anesthetics.

INTRODUCTION: Intra-articular (IA) corticosteroids are used extensively for the treatment of patients with knee osteoarthritis pain. In clinical practice, local anesthetics are frequently combined with corticosteroids prior to IA injection to provide rapid-onset analgesia. From this common practice there is no evidence to suggest that the addition of local anesthetics to corticosteroid preparations, including triamcinolone acetonide (TA), alters the physical properties or efficacy of the corticosteroid. Triamcinolone acetonide extended-release (TA-ER, formerly FX006) is a novel, microsphere-based TA formulation that demonstrated analgesic efficacy in phase 2 and 3 randomized controlled trials. METHODS: The current study assessed the compatibility of TA-ER and lidocaine, ropivacaine, and/or bupivacaine in vitro. The TA-ER and local anesthetic mixtures were assayed for changes in syringeability, pH, particle size, percentage free drug, purity, and appearance compared with TA-ER alone. RESULTS: By these measures, the combination of local anesthetics with TA-ER did not negatively impact the chemical or physical properties of TA-ER when compared to TA-ER controls. CONCLUSION: These results demonstrate that lidocaine, bupivacaine, and ropivacaine are physically and chemically compatible with TA-ER, suggesting that local anesthetic solutions can be added to TA-ER preparations in clinical practice without adversely affecting TA-ER in vitro product characteristics. FUNDING: Flexion Therapeutics, Inc.

Stability and recovery of DIFICID(®) (Fidaxomicin) 200-mg crushed tablet preparations from three delivery vehicles, and administration of an aqueous dispersion via nasogastric tube.

Fidaxomicin is approved for the treatment of adults with Clostridium difficile-associated diarrhea, many of whom have difficulty swallowing an intact tablet. The study objective was to evaluate the stability and recovery of crushed DIFICID(®) (fidaxomicin) 200-mg tablets dispersed in water, applesauce, or Ensure(®) brand liquid nutritional supplement, and to determine the recovery of fidaxomicin from the administration of an aqueous dispersion of a crushed DIFICID(®) tablet through a nasogastric (NG) tube. DIFICID(®) tablets were crushed and dispersed in water, applesauce, or Ensure(®). The stability and recovery of fidaxomicin were evaluated over 24 h in these vehicles. In a separate experiment, the ability to recover a full dose of fidaxomicin when administering as an aqueous dispersion through an NG tube was assessed. When DIFICID(®) tablets were crushed and dispersed in water, the active ingredient, fidaxomicin, was stable for up to 2 h at room temperature. Additionally, it was stable for up to 24 h in dispersions with applesauce or Ensure(®). Recovery of fidaxomicin after crushing and dispersing in any of the three vehicles studied ranged from 95 to 108 %, which is within the normal range of individual tablet variability. When crushed, dispersed in water, and administered through an NG tube, the average recovery of fidaxomicin was 96 %. Stability and recovery of fidaxomicin were confirmed when DIFICID(®) tablets were crushed and dispersed in water, applesauce, or Ensure(®). In addition, administration of an aqueous dispersion of a crushed tablet through an NG tube is supported by acceptable recovery of fidaxomicin.

Plate number requirements for establishing method suitability.

Establishing the suitability of an analytical system has become a routine requirement in the testing of modern pharmaceuticals. Acceptable parameters that illustrate the system is performing as intended and in an equivalent manner to the original validation are often set at the time of method validation and transferred with the method to the production laboratory. For chromatographic methods, these parameters include--but are not limited to--resolution, tailing, and plate number specifications. Transferring methods is often a seamless transition from research to quality control. However, far too often the quality group receives arguably "overzealous" and strict requirements for the method. More specifically, chromatographic methods get issued with plate number specifications that far exceed the minimum number required to achieve sufficient resolution of the analytes. Presented here is a discussion of the setting of realistic plate number specifications that still maintain the minimum resolution of the chromatographic critical pair.