Focus on: Lactic Acid in Pharmaceuticals

How is lactic acid used in the pharmaceutical industry? Let us count the ways.

As a chemist I can think of one that stands out (as a chiral synthon), but in fact there are at least four other important applications for lactate and derivatives, which we will examine individually.

• Hemofiltration and peritoneal dialysis for kidney failure

Kidney patients on standard dialysis need to have fluids replaced with something (between 20 and 30 liters of fluid are removed from patients during a 5-hour dialysis session), and that something is a pharmaceutical-grade lactate solution.

Parenteral dialysis replaces machine-based dialysis in some instances.

A second option for kidney failure, continuous ambulant peritoneal dialysis (CAPD), uses the lining of and organs residing in the peritoneal cavity as the "dialysis membrane." CAPD works quite well for patients who can tolerate it. Until recently, sodium acetate was used as the dialysate fluid, i.e. it was infused into the patient through a permanent catheter inserted through the navel; waste material emptied into a drainage bag. Today L(+) lactate, a normal constituent of the blood, is used instead of acetate due to a lower incidence of side effects.

• Biopolymers for advanced drug delivery

Biodegradable polymers are not only changing the way drugs are delivered, they are also making it possible to administer pharmaceuticals which are too toxic or too unstable to be ingested or injected (for more information see: "Gel Implants: Novel Delivery for Hydrophobic Drugs" and "Fuisz Technologies Adds Ceform, Shearform Manufacturing").

Lactate copolymer microspheres are vehicles for sustained-release drug delivery.

For implantable drug delivery, the materials of choice are lactide-glycolide copolymers, which dissolve in the skin and are absorbed into the body.

• Ammonium lactate for dry skin disorders

Another important group of lactate applications involves using the material directly or indirectly in pharmaceutical preparations. Topically applied lactic acid salts, particularly ammonium lactate, are used to treat severe dry skin or to mitigate the drying or irritating effects of topical corticosteroids.

• Mineral lactate formulations for diseases as such as anemia, hypertension, and osteoporosis

Since lactic acid and its salts are readily accepted by the body, lactate is an ideal vehicle for introducing therapeutic minerals. In general these preparations have advantages of good tolerance and pleasant or neutral taste (when ingested or applied topically). Some of the more important mineral lactates are calcium lactate (for osteoporosis, hypertension, tooth decay), ferrous lactate (anemia), magnesium lactate (hypertension, muscle weakness), manganese lactate (glucose intolerance), and zinc lactate (skin disorders).

• Chiral Synthesis

The importance of chiral chemistry has been stressed in these pages countless times. Pharmaceutical processes will continue to rely on natural product chiral building blocks, among which lactic acid is one of the most important. Both (R) and (S) isomers are now available in optical purities approaching 100%. Pharmaceutical manufacturers love chiral synthons like lactic acid because they are inexpensive, nontoxic, synthetically versatile, and lead to products with any desired stereochemistry.

Chemical structure of lactate, the anion of lactic acid

Some examples of chemical transformations that transform lactic acid into pharmaceutical building blocks:

• Halogenation of lactic acid esters yields 2-halo-propanoic acid esters
• Acylation of the secondary hydroxyl group creates more reactive lactate derivatives
• Reducing the acid group yields optically active propanediol derivatives
• Mesylation or tosylation of the hydroxyl group leads to novel substitution products, e.g. halides, sulfides, and amino acids
• Alkylation or arylation of the hydroxyl group leads to chiral ethers
• Conversion to amides by reaction with amines gives rise to chiral hydroxyamides and hydroxyamines

For more information: Hans van der Pol, Market Development Manager, Purac America, Inc., 111 Barclay Blvd., Lincolnshire Corporate Center, Lincolnshire, IL 60069. Tel: 847-634-6330.

By Angelo DePalma