Glycine

Basic Information

Name: Glycine

CAS No: Aminoethanoic acid [56-40-6]

Functional Categories

Buffering agent Bulking agent Dietary supplement Freeze-drying agent Tablet disintegrant Wetting agent

1. Nonproprietary Names

BP: Glycine JP: Glycine PhEur: Glycine USP-NF: Glycine

2. Synonyms

Aminoacetic acid; 2-aminoacetic acid; E640; G; Gly; glycinum; glycoamin; glycocoll; glycoll; glycolixir; glycinium; Hampshire glycine; padil; sucre de ge´latine.

3. Chemical Name & CAS Registry

Aminoethanoic acid [56-40-6]

4. Empirical Formula & Molecular Weight

C2H5NO2 , 75.07

5. Structural Formula

6. Applications

Glycine is routinely used as a cofreeze-dried excipient in protein formulations owing to its ability to form a strong, porous, and elegant cake structure in the final lyophilized product.(1–3) It is one of the most frequently utilized excipients in freeze-dried injectable formulations(4) owing to its advantageous freeze-drying properties. Glycine has been investigated as a disintegration accelerant in fast-disintegrating formulations owing to its excellent wetting nature.(5,6) It is also used as a buffering agent and conditioner in cosmetics. Glycine may be used along with antacids in the treatment of gastric hyperacidity, and it may also be included in aspirin preparations to aid the reduction of gastric irritation.(7)

7. Description

Glycine occurs as a white, odorless, crystalline powder, and has a sweet taste.

8. Pharmacopeial Specifications

See Table I.

9. Typical Properties

Acidity/alkalinity pH = 4 (0.2 M solution in water) Density 1.1607 g/cm3 Melting point 232–2368C Solubility see Table II.

10. Stability & Storage

Glycine starts to decompose at 2338C. Store in well-closed containers. Glycine irrigation solutions (95–105% glycine) should be stored in single dose containers, preferably type I or type II glass

11. Incompatibilities

Glycine may undergo Maillard reactions with amino acids to produce yellowing or browning. Reducing sugars will also interact with secondary amines to form an imine, but without any accompanying yellow-brown discoloration.

12. Method of Manufacture

Chemical synthesis is the most suitable method of preparation of glycine. Amination of chloroacetic acid and the hydrolysis of aminoacetonitrile are the favored methods of production.(

13. Safety

Glycine is used as a sweetener, buffering agent, and dietary supplement. The pure form of glycine is moderately toxic by the IV route and mildly toxic by ingestion. Systemic absorption of glycine irrigation solutions can lead to disturbances of fluid and electrolyte balance and cardiovascular and pulmonary disorders.(7) LD50 (mouse, IP): 4.45 g/kg(9) LD50 (mouse, IV): 2.37 g/kg LD50 (mouse, oral): 4.92 g/kg LD50 (mouse, SC): 5.06 g/kg LD50 (rat, IV): 2.6 g/kg LD50 (rat, oral): 7.93 g/kg LD50 (rat, SC): 5.2 g/kg

14. Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of the material handled. When heated to decomposition, glycine emits toxic fumes of nitrogen oxides.

15. Regulatory Status

GRAS listed. Accepted for use as a food additive in Europe. Included in the FDA Inactive Ingredients Database (IM, IV, SC injections; oral; rectal) and approved for irrigant solutions. Included in parenteral (powders for injection; solutions for injection; vaccines; kits for implant) and nonparenteral (orodispersible tablets/oral lyophilizate; powders for inhalation; powders for oral solution; tablets) formulations licensed in the UK.

16. Related Substances

Glycine hydrochloride; sodium glycinate. Glycine hydrochloride Empirical formula C2H5NO2HCl Molecular weight 111.5 CAS number [6000-43-7] Melting point 1828C Comments Hygroscopic prisms from hydrochloride. The EINECS number for glycine hydrochloride is 227-841-8. Sodium glycinate Empirical formula C2H4NO2Na Molecular weight 97.1 CAS number [6000-44-8] Melting point 197–2018C Comments The EINECS number for sodium glycinate is 227-842-3.

17. Comments

Anhydrous glycine exists in three polymorphic forms a, b, and g, (10) which can have implications for product stability in lyophilized systems. The b form is generally produced during freeze-drying.