COMPARATIVE ASSESSMENT OF AERODYNAMIC PROPERTIES OF SALBUTAMOL PRESSURIZED METERED DOSE INHALERS

The aerodynamic properties of the developed generic product Salbutamol metered dose inhaler 100 μg/dose and Salbutamol-Teva metered dose inhaler 100 μg/dose using apparatuses A, C, D and E in accordance with the general article 2.9.18 of the European Pharmacopoeia have been studied. In vitro equivalence of the generic product and the comparator with regard to such aerodynamic characteristics as the fine particle dose, the particle size distribution, the relative amount of salbutamol passed through the apparatus stages, the mass median aerodynamic diameter (MMAD), and the geometric standard deviation (GSD) has been shown. It is shown that the device A is useful for testing of the respirable fraction, and the apparatuses D and E are suitable for the assessment of the particle size distribution, MMAD and GSD

QUALITY RISK MANAGEMENT FOR SALBUTAMOL PRESSURIZED METERED DOSE INHALERS

The risks for the functional characteristics of Salbutamol pressurized metered dose inhaler (pMDI), such as the uniformity of delivered dose, the distribution of salbutamol particles at the stages of the Andersen impactor (apparatus D), and the respirable fraction, were studied and identified. It is shown that these risks can be associated with the solubility of salbutamol sulfate (SS), the formulation of pMDI, the water content in the SS and ethanol, as well as the particle size distribution of SS. A relationship is shown between the particle size distribution of the SS, the rate of their sedimentation and the performance characteristics of the preparation. The properties of SS crystals are investigated and the possibility of enantiomers presence is shown. The risks associated with the production process, the materials of the primary packaging and the correctness of the quality control procedures are discussed. It is shown that the use of containers made of aluminum alloy EN AW-5052-0 without internal coating does not pose the risk of the release of elemental impurities into the preparation. Unjustified replacement of actuators may pose a risk to the performance characteristics of Salbutamol pMDI and in vitro equivalence as compared with the reference medicinal product

LABORATORY EQUIPMENT DURING PHARMACEUTICAL DEVELOPMENT OF SEMI-SOLID PREPARATIONS

Introduction. When developing drugs it is necessary to use laboratory equipment that simulates pilot and industrial equipment. For the production of semi-solid preparations the key equipment are rotor-stator dispersers and vacuum reactors-homogenizers.Aim. Investigation of the functional characteristics of laboratory equipment: Megatron® MT 1-50 dispersant SHS F/2 (Kinematica AG, Switzerland) and the RP-5 vacuum homogenizer reactor (Promvit, Ukraine).Materials and methods. During development a generic product Penciclovir cream 1% the initial particle size in suspension of penciclovir and particle size after grinding were studied by optical microscopy and laser diffraction methods. In a cream made in the reactor, the particle size of the dispersed phase of the o/w emulsion and suspension, as well as the absence of air bubbles, were determined by optical microscopy. The assay of penciclovir in 9 samples of the cream taken from the reactor-homogenizer was performed by liquid chromatography. By the of rotational viscometry method the rheological properties of the cream were studied. By the inductively coupled plasma atomic emission spectroscopy the getting of metal impurities from the disperser and the reactor-homogenizer into the suspension and cream were investigated.Results and discussion. With an increase in the rotor speed, the particle size of penciclovir in suspension decreases. The disperser effectively performs its function at a rotor speed of 25,000 rpm. In a cream made in the reactor, the deviations in the quantitative content of penciclovir from the average value in each sample are within the uncertainty of the analytical procedure, which indicates its uniform distribution. The reactor provides effective dispersion and uniform distribution of the oil phase, prevents the formation of a gas emulsion and allows getting a cream that, according to its rheological properties, corresponds to the reference preparation Fenistil® Pencivir cream 1%. In the production process metal impurities were not emitted into the suspension and the cream from the equipment.Conclusion. The disperser and the reactor during the production of cream with penciclovir are suitable for their intended use. It is rational to combine these two types of equipment at the sites for the production of semi-solid preparations. The disperser can also be used to produce emulsions with a very small particle size of the dispersed phase