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Tuesday, 04 March 2014 11:24

Technical Report: Antimicrobial Effectiveness Testing of Antihistamine and Corticosteroid in LoxaSperse™ Dispersion

Introduction:

illus-loxasperse 30-4701 capsule-sm

LoxaSperse is a powder excipient base used for nebulization and irrigation. LoxaSperse is a blend of specially micronized xylitol with an optimized ratio of micronized poloxamers, designed to improve the dispersibility and solubility of active pharmaceutical ingredients (APIs) (PCCA, 2013). The use of xylitol and poloxamers in nebulization and irrigation is thoroughly referenced in the literature and there is ample evidence of their safety and efficacy (Durairaj et al., 2006; Jagannath et al., 1995; Plataki et al., 2011; Zabner et al., 2000).

Fluticasone propionate is one of the most prescribed inhaled corticosteroids in the United States, being the preferred therapy for persistent asthma by acting directly on the pulmonary airways through topical anti-inflammatory effects (Colice et al., 2013). Levocetirizine dihydrochloride is a second-generation antihistamine for the relief of symptoms associated with allergic rhinitis and uncomplicated skin manifestations of chronic idiopathic urticaria. It is known that current treatment options for allergic rhinitis include antihistamines and corticosteroids (Singh-Franco et al., 2009).

In order to verify the effectiveness of LoxaSperse formulations against microbial activity, capsules containing LoxaSperse with fluticasone propionate alone and in combination with levocetirizine dihydrochloride were mixed with sterile water. The final suspensions designed for nasal administration and local effect were assayed by AET methodology for 7 days.

Abstract:

LoxaSperse™ is a powder excipient base used for nebulization and irrigation designed to improve dispersibility and solubility of Active Pharmaceutical Ingredients (APIs). PCCA tested the performance of LoxaSperse formulations containing fluticasone propionate alone and in combination with levocetirizine dihydrochloride, and measured its efficacy against microbial activity when mixed with sterile water. The intent was not to determine clinical efficacy of the API(s) used as antimicrobials but to determine the ability of the dry powder preparation to resist microbial growth. The Antimicrobial Effectiveness Test (AET) was performed at 0.5h, 6h, 28h and 168h – serially diluted, and plated for colony counts. LoxaSperse formulations required 0.5h to significantly reduce and completely eliminate viable S. aureus and P. aeruginosa. The same effect against viable E. coli and C. albicans required 168h. LoxaSperse formulations prevented A. niger proliferation over 7 days of testing. The results of this study demonstrate that accidental or intentional contamination of the finished or reconstituted preparation did not result in microbial growth.

Conclusions:

Both formulations containing LoxaSperse required 0.5h to significantly reduce and completely eliminate viable S. aureus and P. aeruginosa and no bacterial growth was observed in the solutions up to 7 days. This behavior characterizes a 2-Log to 3-Log reduction in viable bacterial cells. E. coli counts were reduced over time and completely killed in 7 days while C. albicans was killed at 7 days. A. niger remained viable throughout the test. The chosen formulas when intentionally contaminated with microorganisms specified in USP <51> resisted microbial growth. Further, this study demonstrated these formulations after reconstitution were not at risk or did not support microbial growth.

Download the complete PDF detailing the results of this study.

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