T&E - Analítica






INHALATION (MDI-DPI-NASAL SPRAY)

ABOUT INHALERS

 

The name itself defines as substance to be inhaled in the product administration process. The USP Pharmacopoeia classifies these products as follows:

 

Aerosol: pressurized for topical use;

Nasal spray: aerosol or manual pressure;

Inhalation: may be suspensions, solutions or powders that are released to the pulmonary absorption (pressure of a gas / manual pressure / aspiration);

 

SPRAYs: liquid droplets dispersed in air manually or pressurized

MDI’s: (Metered Dose Inhaler), pressurized solution or suspension

DPI’s: (Dry Powder Inhaler) Dry Powder Inhaler (IPS)

 

Measuring Units for Dispersions

·         1mm = 1.000 mm           

·         1 mm =1.000nm = 1.000mm

·         1m = 10-3 mm

·         1mm = 10-6 mm = 1 nm     

·         1mm = 1 nm = 10Å (Angstron )

 

·         True solutions: the particles are smaller than 1 millimicron (1 nanometer)

·         Colloidal solutions: particles between 1 and 100 millimicrons (100 nanometers)

·         Suspensions: particles larger than 100 millimicrons (0.1 microns)

 

Considering to be a product to be inhaled through the airways, one of the factors or perhaps the main one is the particle size. The mean diameters are relative to the small particles dispersed in gaseous medium or vapor medium that remain for a certain period of time suspended in the atmosphere. The formation of the particle can be obtained as follows:

 

     I.        Breakdown of larger particles (common dust);

   II.        Pressure reduction (fine solids, solids / liquids of medium volatility);

 III.        Volatilization by heating (inhalants) or high volatility (pendants);

 IV.        Mechanical drag of small solid or liquid particles-Aerosols (insecticides / deodorants / sprays);

        Drag:

                     I.        By means of propellant gas (pressurized);

                   II.        By means of mechanical pressurizing through atomizers;

 

Some known forms of particles in the aerodispersóides can be observed below:

 

 

 

 

The objective of the small mean diameter is to reach distant lung areas and penetration via the nasal via capillaries. The figure below shows the distant regions to be reached by the drug.

 

 

The aerodynamic distribution of the particles can be observed in the figure and the graph corresponding to this distribution.

 

 

 

 

The Analytical T&E Center is authorized by ANVISA and INMETRO in all tests on the pharmaceutical forms Sprays-MDIs and DPIs, as well as in the tests described in the Technical Note:

No. 001/2013 / CEFAR / GTFAR / GGMED / ANVISA.

 

POPULATION BIOEQUIVALENCE:

 

This is a statistical study obtained on the analytical results of the different inhalation measuring equipment. Population Bioequivalence is a decisive factor for the referral of the Pharmaceutical Bioequivalence study, and the number of measurements on determined quantity of samples are values directed by ANVISA. In the case of an approval of the Pharmaceutical Equivalence of Concomitant Inhalation in approval in the study of Population Bioequivalence the results can be presented before the in vivo study to evaluate the ANVISA.

 

The T&E Analytical Center offers the following studies:

 

     I.        PHARMACEUTICAL EQUIVALENCE,

   II.        POPULATION BIOEQUIVALENCE,

 III.        QUALITY CONTROL ISO 17025 (Reblas)

 IV.        BIOEQUIVALENCE/BIOAVAILABILITY PHARMACEUTICAL.

 

 

ANALYTICAL TECHNIQUES

 

IDENTIFICATION AND QUANTIFICATION:

  

Every study begins with a protocol and ends with a Report and Certificate as standardized by ANVISA. The methodologies adopted are preferably pharmacopoeial (Brazilian Farm, American Farm, British Farm, European Farm, Japanese Farm), and when none of these compendia is available, we can propose the development of a methodology for the products or use of the methodology provided by the contracting company, performing prior to the conduct of the study a full or partial validation according to RE 899/2003. Any amount of sample required for the execution of the studies is carefully accounted for in accordance with the definition of current legislation (RDC 31/2010, article 27) and other legislation, regarding the acquisition, control of substances present in Administrative Rule 344/98, area for manipulation, retention, etc. The documentation: is archived at the center for a period of 5 years and the provision for consultation at any time by the contractor or regulatory agency. The drugs remain in our retention for a period of one (01) year after the date of the drug that has the highest expiration date used in the study and previously decharacterized when performing the discard.

 

The analytical techniques used for identification and quantification use methods indicative of stability, that is, methodologies validated according to the current norm. The main techniques are:

 

·         Gas-phase chromatography (GC-FID-ECD-TCD-MS);

·         Liquid phase chromatography - UPLC e or HPLC and different detection systems (detectors);

·         LC-MS / MS: Mass Spectrometry coupled to HPLC or UPLC;

·         ICP-OES (Induced-Simultaneous and Sequential Plasma);

·         AA - (Atomic Absorption)

·         FC (flame photometry).

·         Ultraviolet and / or Visible Light Absorption

·         Determination of peak purity using DAD.

·         Microbiological assays

·         Wet testing

·         INHALATION

·         NGI - Generation Pharmaceutical Impactor

·         ACI - Andersen Cascade Impactor

·         MSLI- Multi-Stage Liquid Impinger

·         DUSA- Dosage Unit Sampling Apparatus

·         ACI GLASS IMPINGER - ACI spray balloon test

·         SPRAY PATTERN - Spray-Pen Pattern

·         SPRAYTEC - Laser Particle Analyzer

·         INTERNAL PRESSURE MEASUREMENT

·         AUTOMATIC ACTUATORS

·         Other specific;

 

Note: Other techniques can be used, always depending on the structure of the molecule. Such methodologies shall be accompanied by scientific explanation and validated in accordance with the resolution in force.