COMPARATIVE ANALYSIS OF THE IN VITRO EQUIVALENCE OF METERED AEROSOL INHALERS CONDUCTED BY THE NEW GENERATION IMPACTOR
https://doi.org/10.15690/pf.v9i5.458
Abstract
Aim. To compare in vitro the aerodynamic particle size distributions of original and generic inhalers, which contain both fluticasone (FP) and salmeterol (SM).Material and methods. The Next Generation Impactor (NGI; Copley Ltd., UK) was used to assess the particle size distribution and aerosol quality of two products to determine the equivalence in the aerosol released from the device. The first formulation was Seretide (SM/FP) 25/250 μg, an original SM/FP fixed combination developed by GlaxoSmithKline. The second formulation tested was Tevacomb 25/250 μg (SM/FP), the generic SM/FP fixed combination produced by Cipla. The mass of FP and SM recovered from each stage of impactor was quantified via high performance liquid chromatography (HPLC). The impactor results were statistically evaluated by log transformation of the single data NGI. Results. Statistically significant differences were seen between the deposition profile of Seretide and Tevacomb obtained using the NGI. Evaluating the single stages results in estimation of nonequivalence for all stages except stage 5 (FP) since their confidence intervals (CI) were out of the range of the tight conventional bioequivalence limits of Ѓ} 15 % (0,85–1,18). Also differences were observed by number of parameters, including the fine particle dose (FPD), emitted dose (ED), mass median aerodynamic diameter (MMAD), and geometric standard deviation (GSD) of SM and FP. Conclusion. These in vitro findings suggest that the particle size distributions of the generic formulation Tevacomb is not equivalent to that of the original product Seretide.
About the Authors
L. A. Trukhacheva
Sechenov First Moscow State Medical University, Russian Federation
Russian Federation
Russian Federation
N. V. Gorpinchenko
Sechenov First Moscow State Medical University, Russian Federation
Russian Federation
Russian Federation
S. P. Dementyev
Sechenov First Moscow State Medical University, Russian Federation
Russian Federation
Russian Federation
References
1. Федеральный закон Российской Федерации от 12 апреля 2010 г. № 61-ФЗ «Об обращении лекарственных средств».
2. ЕМЕА, The rules governing medicinal products in the European Union. Investigation of Bioavailability and Bioequivalence. 1998; 3С: 231–244.
3. WorldHealth Organization, 1996, WHO Expert Expert Committee on Specifications for Pharmaceutical Preparations: thirty-fourth report. WHO Technical Report Series No. 863, Geneva. 1996. Р. 114–154.
4. European Medicines Agency (EMA), Committee for Medicinal Products for Human Use (CHMP): Guideline on the requirements for clinical documentation for orally inhaled products (OIP) including the requirements for demonstration of therapeutic equivalence between two inhaled products for use in the treatment of asthma and chronic obstructive pulmonary disease (COPD) in adults and for treatment of asthma in children and adolescents. January 22, 2009. Available at: http://www.emea.europa.eu/pdfs/human/ewp/415100enfin.pdf
5. Health Canada: Guidance to establish equivalent or relative potency of safety and efficacy of a second entry short-acting eta2-ago nist metered dose inhaler (April 1999). Available at: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applicdemande/guide-ld/inhal-aerosol/mdi_bad-eng.php (Accessed August 3, 2011).
6. Derendorf H. Pharmacokinetic and pharmacodynamic properties of inhaled corticosteroids in relation to efficacy and safety. Respir. Med. 1997; 91: 22–28.
7. Johnson M. The pharmacology of salmeterol. Life Sciences. 1993; 52: 2131–2143.
8. Elkout H. A retrospective observational study comparing rescue medication use in children on combined versus separate long-acting beta-agonists and corticosteroids. Arch. Dis. Child. 2010; 95 (10): 817–821.
9. Marple V., Roberts D., Romay F. Design of the next generation pharmaceutical impactor. Drug Delivery to the Lungs. 2000, 11, 127–130.
10. European Pharmacopoeia 5.0: Chapter 2.9.18. Preparations for inhalation: Aerodynamic assessment of fine particles. 11. United States Pharmacopiea: General Chapter < 601 > Aerosols, nasal sprays, metered dose inhalers and dry powder inhalers. USP. 34: 218.
11. Weda M., Geuns E., Vermeer R., Buiten N. et al. Equivalence testing and equivalence limits of metered dose inhalers and dry powder inhalers measured by in vitro impaction. Eur. J. Pharm. Biopharm. 2000; 49: 295–302.
12. Smyth H., Beck V., Williams D., Hickey A. The Influence of formulation and spacer device on the in vitro performance of solution chlorofluorocarbon-free propellant-driven metered dose inhalers. AAPS PharmSciTech. 2004; 5 (1): 235–241.
Review
For citations:
Trukhacheva L.A., Gorpinchenko N.V., Dementyev S.P. COMPARATIVE ANALYSIS OF THE IN VITRO EQUIVALENCE OF METERED AEROSOL INHALERS CONDUCTED BY THE NEW GENERATION IMPACTOR. Pediatric pharmacology. 2012;9(5):70-74. (In Russ.) https://doi.org/10.15690/pf.v9i5.458
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