ABOUT THE DISSOLUTION DOSE
The analytical study for obtaining the DISSOLUTION DOSSIER is based on Resolution DRC 31 of August 11, 2010, in this specific case in Chapter II, of the PHARMACEUTICAL EQUIVALENCE Study.
Art. 14: In the absence of dissolution method described in official compendium, specific norms or regulations approved / endorsed by Anvisa, it is the responsibility of the Sponsor of the Study the report of development and validation of the method of dissolution that must be realized as recommended in guides and contain data demonstrating that the method is discriminative.
I. The Center Responsible for the Study shall file a copy of the dissolution method development report provided by the Study Sponsor;
II. The Center Responsible for the Study must proceed to the partial validation of the method of dissolution developed and transferred by the Sponsor of the Study; and
III. The dissolution development report shall contain at least the following information:
a) Quantitative evaluation of the solubility of the active substance in the range of physiological pH (1.2 to 6.8), considering the temperature of 37 ° C ± 1 ° C, according to, for example, the phase diagram method for analysis of solubility. The evaluation requires that increasing amounts of the active substance be tested in fixed volume of at least three different media such as, for example, at pH 1.2; 4.5 and 6.8;
b) Demonstration that the dissolution medium is most suitable for the active substance in the pharmaceutical form under study. The demonstration requires the investigation of dissolution curves in the range of physiological pH (1.2 to 6.8), as, for example, at pH 1.2; 4,5 and 6,8, considering the temperature of 37 ° C ± 1 ° C;
c) Demonstration that the apparatus, rotation and filters used in the sampling procedure are most appropriate to the active substance and to the pharmaceutical form under study;
d) Justification of the need to use anchors, when applicable;
e) Proof of the need to use surfactants, as well as the quantity used, when applicable;
f) Demonstration and justification of the choice of the value of Q (quantity of dissolved active substance expressed as a percentage of the labeled value of the unit dose); and
g) Justification for the need to apply the deaeration method, when applicable.
§1º The report of development of the method of dissolution may also be adopted when the method of dissolution described in official compendium, norms or specific regulations approved / endorsed by Anvisa, is not suitable for the product, provided duly proven.
§2º The pH of the dissolution medium should be in the physiological range (1.2 to 6.8). If it is necessary to use another pH range, this must be justified in the development report of the dissolution method.
§3º The Study Sponsor may contract Anvisa Pharmaceutical Equivalence Center for the development and validation of the dissolution method.
In general, when the dissolution dossier is necessary: In the absence of scientific definition of the dissolution medium, the Dissolution Dossier should be studied to obtain the ideal or representative dissolution medium. Thus, the main steps to obtain the Dissolution Dossier can be summarized in:
· Determination of the solubility of the active and formulated input;
· Filter choice test;
· Apparatus search test;
· Anchor test;
· Surfactant assay;
· Aeration test;
· Determination of the value of Q;
· Challenge of Q according to USP;
· Validation of the methodology of content;
The dissolution systems offered by the T&E Analytical Center have the following devices:
· USP Apparatus 1 - Rotary Basket;
· USP Apparatus 2 - Blades;
· USP Apparatus 5 - Shovel on disc;
· USP Apparatus 6 - Rotary Cylinder;
Note: Apparatuses 5 and 6 are used for transdermal, adhesive, etc.
Conventional vats are glass or polymeric, transparent or amber. The volume and shape of the vats are important for obtaining the results.
The normal tank of a dissolutor has a volume of 900mL, cylindrical open containers with hemispherical bottom.
· Cube of 900mL – hemispheric fund;
· Cube of 900mL (Peek Vessel) - internal pre-drilling bottom;
· Cube of 500mL – hemispheric fund;
· Set of mini vats and mini spades - 250 mL;
Note: change of tank, such as Peek Vessel, ANVISA should be consulted to conduct the tests, since it has a higher intensity vortex.
The analytical techniques used, are for determination of the content, in this way it becomes necessary, validated methodologies indicative of stability. The main techniques are:
· Gas-phase Chromatography (GC-FID-ECD-TCD-MS-Head Space);
· 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;
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.