Lecture 3(29-09-16) learning objectives • Explain how alkalinity develops in the glass? • Describe the factors affecting alkalinity. • Determine the effects of alkalinity on Pharmaceutical dosage forms. • "The capacity of water for neutralizing an acid solution." - U.S. Geological Survey, 2010
• Alkalinity is a measure of the ability of a
solution to neutralize acids to the equivalence point of carbonate or bicarbonate. • Units: mEq/L (milliequivalent per liter). • Commercially, ppm or parts per million. • In all glass, the sodium and potassium oxides are hygroscopic; the surface of glass absorbs moisture from the air. • Moisture and carbon dioxide in air causes the Na2O or NaOH and K2O or KOH to convert to sodium (Na2CO3) or potassium carbonate (K2CO3) which are extremely hygroscopic. • In salt water, the Na+ and K+ carbonates in unstable glass may leach out, leaving only fragile, porous hydrated silica (SiO2 ) network. This causes the glass to fade, crack, pit and gives surface of glass a frosty appear. • Large surface areas • Long contact times with the atmosphere Effect of Glass Alkalinity on Pharmaceutical Products • Use of buffered solution (stability retained) • Use of unbuffered solution (stability lost) • Borosilicate glass (stability retained) • Soda lime glass (stability lost) • Alkalinity of a solution is the capacity of it to react with a strong acid (usually H2SO4) to a predetermined PH. • The alkalinity of a solution is usually made up of carbonate, bicarbonate, and hydroxides. • Similar to acidity, the higher the alkalinity is, the more neutralizing agent is needed to counteract it. •The scanning electron micrographs showed surprising differences in the appearance of the surface region.
Sulfur treatment of ampoules was associated with
a pitting (abrasions) of the surface and the presence of sodium sulfate crystals. The sulfur treatment of vials altered the glass surface in a characteristically different way Test of alkalinity of glass Alkalinity testing(chemical test) 1.Alkalinity test for whole glass • Apparatus used: Autoclave Equipped with a thermometer, a pressure gauge, a vent and a rack. • Hardened-steel mortar and pestle. o 8 Inch-sieves No. 20, 40 and 50 along with the pan and cover o 250ml conical flask and volumetric flask made of resistant glass • Special distilled water: having a specific conductivity of 0.5 to1 Siemens. • Methyl red solution: Dissolve 24 mg of methyl red sodium in sufficient purified water to make 100ml. if necessary, neutralize the solution with 0.02 N NaOH. • Take not less than 3 from each batch. • Rinse twice the containers thoroughly with distilled water. • Fill each container to 90% of its overflow capacity with the redistilled water. • Cover the unsealed containers with crimped pieces of new tin foil wash thoroughly with acetone. • Place the containers on in autoclave, close the door, leaving the vent open. • Heat until steam release vigorously from the vent and continue heating for 10 min. • Close the vent adjust the heating so that the temperature rises 1°C/min until it reaches 121°C, for 20- 25 min. • Keep the temperature 121°C ± 0.5 °C for 1 hour. • At the end decrease the supply of heat and cool at the rate of 0.5 °C/min, until the internal pressure is equal to the atmospheric pressure. • Open the autoclave and allow the containers to cool at 25 °C. • Titration:
Transfer 100 ml of water from each container add 5
drops of methyl red solution, and titrate with 0.01 N sulphuric acid. • The time elapsing between opening the autoclave and titrating should not exceed 60 minutes. • Carry out Blank Test on 100 ml of water from the same lot, and make the necessary correction.
• The quantity of 0.01N sulphuric acid used for
containers with a capacity of up to 100 ml should be, not more than 0.5 ml and for containers of capacity greater than 100ml, not more than 1.5 ml. 2.Powdered glass test • Take a clean dry empty glass containers 6 or more. • crush it in mortar-pestle. • Crushing and sieving. • Excess of 10g, stored in closed container in desiccator. • Spread the sample on butter paper. • Remove the iron particles from sample. • Transfer sample in a 250ml conical flask • wash it with 30 ml acetone, • swirling 30sec,and decant the acetone. • Dry the contents in flask in oven at 1400C for 20 minutes. • Transfer this powder in another dried conical flask and cool in desiccator. • add 50ml of distilled water. (sample preparation) • In another conical flask (100ml) add 50ml of distilled water. (for blank reading) • Cover both flasks with paper and place in oven at 1210C for 30minutes. • Cool them in desiccators. • Transfer distilled water from sample containing flask in another flask. • Wash glass powder residues with 15 ml special distilled water 4times and • transfer this water in a flask contain main portion • add 5 drops of methyl red. • Titrate against 0.02N H2SO4 until color changes to light pink.
• Titrate the distilled water for blank
determination in the same way.
• Note: Blank reading should be 0.1-0.2ml and
sample reading should be 0.7-0.8ml. 3.Water attack test • Rinse thoroughly 3 or more containers, twice with special distilled water. • Fill each container 90% capacity with distilled water. • Follow procedure of powered glass test except the time of autoclaving =1hour • In a 250ml conical flask, transfer 100ml water from each container, small container combine contents will be use. • 5drops methyl red indicator will be used • Titrate with 0.02N H2SO4.(0.2ml-0.7ml) • Titrate 100ml of special dis. water for blank titration. • Wash the glass thoroughly in running tap water and then soak it in distilled water. • Dry the glass in two baths of alcohol. This treatment will retard the disintegration and also improves the appearance of the glass. • It does not however, always stop the breakdown of the glass. • If applicable, apply an organic lacquer (PVA or Acryloid B-72) to impede disintegration. • For assurance, store the glass in a dry environment with the relative humidity not higher than 40 %. • Parentral glass container: Sulphur treatment