Solkane® 227 pharma and 134a pharma (NEW) - Datasheet

Quality Control and Specifications To date, no monographs have been established for either HFA 227 or HFA 134a in the USA or Europe, so that the specifications are still supplier-related. This is expected to be the status for the next years, although working groups are forming, and a first USP proposal for an HFA 134a monograph has been published [39]. In the case of HFA 134a, two quality standards have already been published: one by the CPMP as mentioned before [1], and one proposed by the FDA in a draft guideline [5]; accordingly, the quality shall comply with these standards. As seen from the table which lists all impurities mentioned in these standards, sophisticated analytical methods are required to identify and detect all impurities without interference from the others. Solvay has developed a GC-MS method especially for this purpose which allows the control of each of the listed impurities at limits of detection LODs) below 1 ppm (v/ v). Solkane® pharma –      Impurities of HFA 134a Proposed by CPMP/FDA   in Comparison to Solvay Quality         Norflurane Norflurane LOD      Pilot Production Production    Limit (ppm) Batches Batches Batches    FDA CPMP Mean results Mean results Limit of Volatile Related Substance (October 98 (July 94 A0150N0001-03 A0150N0013-18 detection   draft guidance) press release) (ppm (v/v)) (ppm (v/v)) (ppm (v/v)) CFC 114a  = 25 = 1000 (1) n.d. n.d. 0.2 HCC 40  = 5 = 50 n.d. n.d. 0.1 HCFC 1122  = 5 – < 1 < 0.5 0.2 HCFC 124  = 100 = 1000 (1) n.d. n.d. 0.3 HCFC 133a  = 5 = 5 n.d. n.d. 0.2 HCFC 22  = 50 = 1000 (1) n.d. n.d. 0.4 HCFC 31  = 5 = 5 n.d. n.d. 0.3 HFC 125  = 5 = 1000 (1) n.d. n.d. 0.2 HFC 134  = 1000 = 1000 (1) 1 14 0.3 HFC 143a  = 10 = 1000 (1) n.d. n.d. 0.2 HFC 152a  = 300 = 1000 (1) n.d. n.d. 0.3 CFC 114  = 5 = 1000 (1) n.d. n.d. 0.2 HFC 134a (assay) = 99.9 = 99.8 > 99.99 > 99.99 – CFC 115  = 5 = 1000 (1) n.d. n.d. 0.1 CFC 12  = 100 = 1000 (1) n.d. n.d. 0.2 HCFC 1122a  = 5 – n.d. n.d. 0.2 HFC 1225ye  = 5 – n.d. n.d. 0.1 HFC 1234yf  = 5 – n.d. n.d. 0.1 HFC 1243zf  = 5 – < 2 n.d. 0.2 HFC 245cb  = 5 = 1000 (1) n.d. n.d. 0.2 HFC 23  = 5 – n.d. n.d. 0.2 HFC 32  = 5 – n.d. n.d. 0.1 HFC 152  = 5 = 5 n.d. n.d. 0.3 HFC 1123  = 5 – n.d. n.d. 0.1 FC 1318my-cis  = 5 – < 2 n.d. 0.1 FC 1318my-trans = 5 – < 2 n.d. 0.1 HFC 1132  = 5 – n.d. n.d. 0.4 HFC 1336mzz  = 5 – n.d. n.d. 0.2 HCFC 123  = 5 = 1000 (1) n.d. n.d. 0.3 HCFC 123a  = 5 = 1000 (1) n.d. n.d. 0.4 HCFC 124a  = 5 = 1000 (1) n.d. n.d. 0.3 HCFC 132b  = 5 = 5 n.d. n.d. 0.4 HCFC 161  = 30 – n.d. n.d. 0.2 HCFC 1121  = 5 – n.d. n.d. 0.1 CFC 11  = 5 = 1000 (1) n.d. n.d. 0.1 CFC 12B1  = 5 – n.d. n.d. 0.3 CFC 13  = 5 – n.d. n.d. 0.1 CFC 113  = 5 – n.d. n.d. 0.3 CFC 1112a  = 5 – n.d. n.d. 0.1 Total unsaturates = 5 = 5 < 2 < 1 – Sum of others  = 50 = 50 n.d. n.d. – Individual unidentified impurities = 5 – n.d. n.d. – Total unidentified impurities = 10 – n.d. n.d. – Any other identified saturated impurity = 5 – n.d. n.d. – Total impurities = 1000 – < 2 14 – (1) Not more than 1000 ppm alone or in combination; n.d.: not detected   Comparison of the FDA draft proposal for impurity limits in pharmaceutical HFA 134a and CPMP specifications with the Solvay Solkane® 134a pharma quality from three pilot and six production batches (mean values)   The Solvay specifications for Solkane® 227 pharma and Solkane® 134a pharma are listed as follows: Solvay Fluor Specifications Solkane® 227 pharma Solkane® 134a pharma Contents ≥ 99.9% vol. ≥ 99.99% vol. Identification Complies with MS library Complies with MS library Water ≤ 10 µg/g ≤ 10 µg/g Non-volatile Matter ≤ 20 ppm (m/m) ≤ 50 ppm (m/m) Volatile Related Substances (Impurity Profile) Described in the Solvay DMF for norflurane (HFA 227) Described in the Solvay DMF for apaflurane (HFA 134a) Acidity ≤ 0.1 µg/g (as HF) ≤ 0.1 µg/g (as HCl)     ASHRAE Nomenclature The American Society of Heating, Refrigerating, and Air Conditioning Engineers (ASHRAE) has created a standard for a Halocarbon Numbering System. In the Halocarbon Numbering System, the first number gives the number of carbon atoms minus one, followed by (in order) the number of hydrogen atoms plus one and the number of fluorine atoms: First number: number of carbon atoms – 1 Second number: number of hydrogen atoms + 1 Third number: number of fluorine atoms All remaining atoms are assumed to be chlorine atoms. An initial zero (indicating a onecarbon compound) is omitted. For example: 1,1,1,2,3,3,3-heptafluoropropane (INN = apaflurane) has: three carbon atoms (3–1=2), one hydrogen atom (1+1=2), seven fluorine atoms (7=7) and no chlorine atoms therefore it is named as HFA 227. When there are two (or more) carbon atoms present, isomers are possible, and these may have identical halocarbon numbers. To distinguish these isomers for ethane derivatives, a lower case letter is added based on the difference in the sum of the atomic masses of the carbon substituents. The designation for the isomer with the smallest difference in the sum of the masses on the two carbon atoms has no letter; the designation corresponding to the next smallest difference has an “a”, the next “b”, etc. Some examples are given below for the isomers of tetrafluoroethane (INN = norflurane). HFA 134 CHF2-CHF2 HFA 134a CH2 F-CF3 The Halocarbon Numbering System for linear three-carbon compounds (propane) is similar to that for two-carbon compounds; however, two letters are required to specify the isomer. The first letter refers to the central methylene) carbon atom of the propane. To assign this letter, one calculates the combined atomic mass of the substituents on this carbon atom in the parent compound containing only H, F and/or Cl). The letter “a” represents the largest mass possible, the letter “b” the next largest, etc. First Suffix           Chemical Group of Central Carbon Atom a – CCl2 – b – CClF – c – CF2 – d – CHCl – e – CHF – f – CH2 – For example: CF3 – CHF – CF3 = HFA 227ea CF2H – CF2 – CF3 = HFA 227ca     Physical Properties Nomenclature   Description Physical Data [SI Units] Thermal Stability Refractive Index   Physical Data [US/UK Units] Thermal Stability Refractive Index   Vapour Table Wet Vapour Range Solkane® 227 pharma[11] [SI Units] Density in g/l Fig. 14: Density of liquid of Solkane® 227 pharma and Solkane® 134a pharma [11] including a 50:50 blend depending on temperature in comparison to CFC blends (CFC 11/12 as 40:60 and CFC 11/12/114 as 18:22:60) [16]   Vapour Table Wet Vapour Range Solkane® 134a pharma[11] [SI Units] Vapour Pressure in bar Fig. 15: Vapour pressure of Solkane® 227 pharma and Solkane® 134a pharma [11] including a 50:50 blend depending on temperature in comparison to CFC blends (CFC 11/12 as 40:60 and CFC 11/12/114 as 18:22:60) [16]   Vapour Table Wet Vapour Range Solkane® 227 pharma[11] [US/UK Units] Density in lb/ft3 Fig. 16: Density of liquid Solkane® 227 pharma and Solkane® 134a pharma [11] including a 50:50 blend depending on temperature in comparison to CFC blends (CFC 11/12 as 40:60 and CFC 11/12/114 as 18:22:60) [16]   Vapour Table Wet Vapour Range Solkane® 134a pharma[11] [US/UK Units] Vapour Pressure in psia Fig. 17: Vapour pressure of Solkane® 227 pharma and Solkane® 134a pharma [11] including a 50:50 blend depending on temperature in comparison to CFC blends (CFC 11/12 as 40:60 and CFC11/12/114 as 18:22:60) [16]   Viscosity in mPa·s Fig. 18: Dynamic viscosity of liquid Solkane® 227 pharma and Solkane® 134a pharma depending on temperature [11]   Surface Tension in mN/m2 Fig. 19: Surface tension of Solkane® 227 pharma and Solkane® 134a pharma depending on temperature [11]     Back