Waterless A/B extraction of pseudoephedrine from tablets Abstract of procedure: reduce pills to powder form soak 12 hours in non-polar solvent rinse with acetone boil in acetone dry thoroughly add base add basing medium (OH, acetone) mix thoroughly extract with non-polar solvent gas or extract with aqueous HCl rinse or acetone flash recrystalize with ISO OH Standard Procedure: 1)If using 30 mg pills with red coating, remove the red coating. Grind pills to powder form. Use a morter and pestle after coffee grinder; texture should be a f ine powder and few coffee grinders get the pills fine enough by themselves. 2) The powdered pill mass should first be soaked in a non-polar solvent. Choice of solvent is dictated by the presence of povidone and/or polyethylene glycol. I f povidone is present, mineral turpentine is the solvent of choice; alternatives include xylene, tolulene, mineral spirits. Suggested time: twelve hours. If pov idone is not present but polyethylene glycol is present, soak in non-polar solve nt for at least six hours. Recommended solvent: xylene, tolulene, mineral spirit s. Decant non-polar solvent. 3) Rinse pill mass with dried acetone, discard acetone. If the pills contain an antihistamine, place pill mass in pyex dish, cover with two to three times its v olume in dried acetone, bring temperature up slowly with hotplate to a steady ge ntle boil with constant ventilation. No open flame or ignition source may be use d. Stir boiling acetone continuously for five minutes, remove from heat, decant acetone. Spread pill mass and allow to dry to complete dryness. 4) Weigh out one gram of NaOH for each gram of available pseudoephedrine in the pill mass. Weigh out one gram of NaCl for each gram of available pseudoephedrine (rock salt is recommended). Combine and grind in coffee grinder to fine powder. Take care to avoid inhalation of powdered NaOH! Mix the combined salt and sodiu m hydroxide with the dry pill mass and stir with a glass rod until the mixture i s evenly and thoroughly mixed. 5)With the pill mass/ sodium hydroxide/ salt mixture in a pyrex beaker of suffic ient depth to allow the addition of three times the pill mass volume of non-pola r solvent, add very dry isopropyl alcohol in small quantities while mixing the m ass with a glass rod; continue adding alcohol and stirring until the pill mass h as the consistency of a thin paste. The pill mass should heat slowly during this step. At no time should the mass become too hot to hold comfortably. If the hea t rises quickly and beyond comfortable temperature to hold, add non-polar solven t immediately. As long as the temperature does not make a quick surge, work the pill mass for at least ten minutes to insure all portions of the pill mass have been exposed to the base. You will observe the color change of the pill mass, mo st usually to a medium yellow or light tan/brown shade. This is expected. Dark b rown indicates the presence of excess water but will not impede the process. 6) Add three times the volume of the pill mass with non-polar solvent. Xylene is recommended. Mix this with the paste very thoroughly, recommended for at least fifteen minutes. Allow to settle, decant the non-polar solvent. Repeat this step
twice. The amount of mixing and the time period may be shortened for the last t wo non-polar soaks. Combine the three volumes of non-polar solvent used to extra ct the freebase pseudoephedrine. 7) Wash the non-polar solvent with warm distilled water wash, cool distilled wat er wash, and a third warm water wash. Continue washing until the washes are clea n. After the third wash, monitor the pH and do not allow it to fall below pH 9. If necessary to remove excess sodium ions, do a NaOH wash of the nonpolar with a 20% NaOH solution. 8) Extract the pseudoephedrine from the non-polar solvent by gassing or by aqueo us HCl addition and evaporation to near dryness, followed with an acetone "flash ." 9) Rinse the collected pseudoephedrine in dry acetone. Dissolve in hot dry isopr opyl alcohol and recrystalize with dry acetone as a second solvent. Repeat the r ecrystalization. Notes and comments: 1) Pill selection: this process was developed with generic antihistamine tablets with 60 mg pseudoephedrine and 2.5 mg tripolidine. It also is effective with ps eudoephedrine sulphate antihistamine tablets with cloropheneramine maleate, and changes the form to the salt form for the reaction. Name brand and generic 120 m g and 240 mg time release pseudoephedrine tablets may be extracted with the proc ess. Yields for the above average 60- 66 percent of available pseudoephedrine hy drochloride by weight. Extraction process yields very clean pseudoephedrine HCl. If the pills are dry matrix formulation such as the time release 120 mg caplets , it is very important that every solvent used be as dry as possible and that th e pill mass not be exposed to excess moisture or allowed to remain exposed and u ncovered. 2) The presoak in non-polar solvent is to remove povidone and mineral turpentine is recommended. Alternatives are soaks in xylene, tolulene, mineral spirits. Mi nimum twelve hour soak for any solvent but mineral turpentine. If povidone is no t listed and you are familiar with the pills and have not encountered povidone i n them even though unlisted, a soak in any of the other suggested non-polar solv ents is done to remove polyethylene glycol. Six hours is sufficient; shorter tim es may be effective but have not been tested by the author. PEG should be solubl e in any of the nonpolar solvents, but if the pills are the 120 time release for mulation (or the "dry matrix" formulation) the author strongly suggests xylene b e used. 3) The acetone rinse is to rid the pill mass of the non-polar solvent. The follo wing acetone boil is to remove tripolidine or chloropheneramine maleate. If ther e are no antihistamines present in the formula, the acetone boil is unnecessary and should not be done. Do not boil the pill mass with the solvent, or with the solvent and acetone combined. Rinse the solvent and then use fresh acetone to bo il. Yield seems to be better is the entire pill mass is allowed to dry thoroughl y before the addition of base. Drying in the microwave on less than full power i s effective, although not particularly recommended. Drying in an electric oven a t low temperature, not to exceed 150 degrees F if also effective to dry the pill mass. 4) If the pill mass is in the least clumpy or hard, grind it to powder again bef ore proceeding. NaOH may be used to base. Gram per gram is probably an excess of NaOH, but it does effect the basing. Sodium carbonate has been used with good s uccess and it provides fewer contaminants to the non-polar solvent that need to be washed out. Baking soda baked completely dry-- 350 degrees for thirty minutes in a shallow dish should be sufficient, yields sodium carbonate. pH Down at the
pool store is sodium carbonate and may also be used for the process. Salt is re commended as an addition to the lye as it provides a moisture absorbing substanc e to help prevent the lye from absorbing moisture immediately on powdering. Lye can be used without grinding it; powdered NaOH seems to give better performance. 5) The selection of solvents to mobilize the HCl is one of choice. On the antihi stamine type pills, MeOH may be used, but is not recommended. Very dry ISO alcoh ol is one recommendation, although dry acetone seems to work very well. If the p ills are time release or dry matrix formulation, dryness is essential to yield. Dry acetone is highly recommended. The addition of the solvent should be a littl e at a time, working the pill mass until a slightly thin paste is achieved. Wate r, including moisture in alcohol or acetone, will tend to speed the basing proce ss up and if NaOH is used it can become hot too quickly and damage the pseudoeph edrine. Care should be taken to select dry solvents. Working the mass thoroughly is thought to be important to yield. Too much alcohol can impede the a/b proces s, and the amount used should be carefully tailored to avoid making the pill mas s runny and diluting the non-polar solvent with alcohol. 6) Xylene is the author's preferred non-polar solvent for extracting the freebas e pseudoephedrine as it is unlikely to contain any significant amount of water s traight from the can, or even after having been used. It is considered to be the solvent of choice for dry matrix formulations. Tolulene and Mineral Spirits hav e been used with equivalent success. Naptha is not a recommended solvent for thi s purpose. 7) The washes will rid the non-polar solvent of any color they aquire from the p ill mass and excess sodium ions. Wash until clean. Save the water washes to chec k for pseudo freebase that may hitch a ride in the water. It can happen. Advantages: works with most pills; safer than solvent boiling techniques; fewer solvents used; less odor; pseudoephedrine HCl obtained is very clean and has few er impurities that affect the reaction, contaminate the red phosphorous, or cont ribute to yield loss. Disadvantages: complex for those unfamiliar with a/b process; risk of damage to the pseudoephedrine during the basing process; low yields if done improperly or too much alcohol used; may allow polyethylene glycol or povidone to be extracted with the pseudoephedrine if proper soaking is not done; some report limited yie lds with the process. Known to be effective with pills containg the following ingredients: Pseudoephedrine HCl 60 mg Tripolidine 2.5 mg corn starch Flavor Hydroxypropyl Methylcellulose lactose Magnesium Stearate Polyethylene glycol potato starch povidone sucrose titanium dioxide patent no. 5098715 210CA01 __________________________
Pseudoephedrine HCl 60 mg Tripolidine 2.5 mg Hydroxypropyl Methylcellulose Magnesium Stearate Polyethylene glycol starch titanium dioxide may also contain: cellulose Dioctyl Sodium Sulfosuccinate Hydroxypropyl cellulose lactose Polysorbate 80 povidone powdered cellulose pregelatinized starch silica gel silicon dioxide sodium starch glycolate stearic acid _______________________________ Pseudoephedrine HCl 60 mg Tripolidine 2.5 mg carnuba wax corn starch flavor Hydroxypropyl Methylcellulose lactose Magnesium Stearate Polyethylene glycol povidone sucrose _________________________________ Pseudoephedrine Hcl 120 mg Candellia Wax Hydroxypropyl Methylcellulose Magnesium Stearate Microcrystalline Cellulose Polyethylene glycol povidone titanium dioxide Pseudoephedrine Hcl 240 mg Candellia Wax Hydroxypropyl Methylcellulose Magnesium Stearate Microcrystalline Cellulose Polyethylene glycol povidone titanium dioxide
