Formulations of injections

Industrial pharmacy assignment
Formulation of injections

1. Formulation of Injections

2. INTRODUCTION Injection are the sterile solution or suspensions of drugs in aqueous or oily vehicle meant for introduction into the body by means of an injectable needle under or through one or more layers of the skin or mucous membrane. Injections should be sterile, isotonic and free from foreign particles, such as dust, fibres etc.

3. Formulation of injections (Solution and suspension) : Solution : A range of excipients may be included in parenteral solutions, including antioxidants, antimicrobial agents, buffers, chelating agents, inert gases, and substances for adjusting tonicity. Antioxidants maintain product stability by being preferentially oxidized over the shelf life of the product. Antimicrobial preservatives inhibit the growth of any microbes that are accidentally introduced while doses are being withdrawn from multiple-dose bottles and act as adjuncts in aseptic processing of products

4. Suspension : A suspension for injection consists of insoluble solid particles dispersed in a liquid medium, with the solid particles accounting for0.5-30% of the suspension. The vehicle may be aqueous, oil, or both. Caking of injectable suspensions is minimized through the production of flocculated systems, comprising clusters of particles ( flocs ) held together in a loose open structure.

5. Excipients in injectable suspensions include antimicrobial preservatives, surfactants, dispersing or suspending agents, and buffers. Surfactants wet the suspended powders and provide acceptable syringe ability while suspending agents modify the viscosity of the formulation.

6. Ingredients : Example : Diazepam 5mg/ml injection .

7. Method of Preparation: This formulation should be prepared according to strict aseptic compounding technique in a laminar airflow hood in a clean room or via isolation barrier technology by a compounding pharmacist validated in aseptic compounding. This is a high-risk preparation.

8. Diazepam injection USP is a sterile solution of diazepam in a suitable medium. It has a pH between 6.2 and 6.9, contains not more than 11.6 USP Endotoxin Units per mg of diazepam, and has an osmolality of about 7,775 mOsm/kg. 1  Because of the cosolvent system used to solubilize the diazepam, care should be taken when diluting this injection.

9. Propylene glycol : Propylene glycol (C 3 H 8 O 2 ) occurs as a clear, colorless, viscous, practically odorless liquid with a sweet taste, somewhat resembling glycerin. It has a specific gravity of 1.038 g/mL, and it is miscible with 95% ethanol, glycerin, and water. 5

10. Ethyl alcohol : Ethyl alcohol, ethanol, grain alcohol, C 2 H 5 OH, MW 46.07) is a clear, colorless, mobile, volatile liquid with a slight, characteristic odor and a burning taste. Alcohol USP refers to 95% ethanol, and dehydrated alcohol refers to 99.5% alcohol. Its specific gravity is between 0.812 and 0.816, and its boiling point is 78.15°C. Alcohol is miscible with glycerin and water.

11. Sodium benzoate : Sodium benzoate (C 7 H 5 NaO 2 , MW 144.11) occurs as a white granular or crystalline, slightly hygroscopic powder. It is generally odorless and has an unpleasant sweet and salty taste. Sodium benzoate is soluble 1 g in 1.8 mL of water and 75 mL of 95% ethanol. It is used as an antimicrobial preservative.

12. Benzoic acid : Benzoic acid (C 7 H 6 O 2 , MW 122.12) occurs as white crystals, scales, or needles with a slight odor. It is somewhat volatile at warmer temperatures, slightly soluble in water, and freely soluble in alcohol.

13. Benzyl alcohol  : Benzyl alcohol (C 7 H 8 O, MW 108.14) is an antimicrobial preservative, disinfectant, and solvent that occurs as a clear, colorless, oily liquid that has a faint, aromatic odor and a sharp, burning taste. Benzyl alcohol has a specific gravity of about 1.045. It is soluble 1 g in 25 mL of water at 25°C and is miscible with ethanol.

14. Uses : Diazepam injection is used to treat  anxiety disorders , alcohol withdrawal symptoms, or muscle spasms. Diazepam injection is also used to treat a seizure emergency called status epilepticus . Diazepam injection is sometimes used as a sedative to help you relax before having surgery or other medical procedure.

15. Common side effects of diazepam injection include: drowsiness, dizziness, nausea, poor coordination, unsteadiness, headache, sleep disturbances, low blood pressure,

16. Example Example : Amikacin for 250 mg/ml injection

17. Method of Preparation: This formulation should be prepared according to strict aseptic compounding technique in a laminar airflow hood in a clean room or via isolation barrier technology by a compounding pharmacist validated in aseptic compounding. This is a high-risk preparation.

18. Amikacin sulfate (Amikin, C 22 H 43 N 5 O 13 .2H 2 SO 4 , MW 781.76) occurs as a white, crystalline powder that is freely soluble in water. It contains the equivalent of not less than 674 mcg and not more than 786 mcg amikacin per mg, calculated on the dried basis. On drying, it loses not more than 13.0% of its weight. It is important to check the label of the bulk amikacin sulfate powder to determine the equivalent amount to be used. Amikacin sulfate should be preserved in a tight container. The injection is colorless to light straw-colored and has a pH ranging from 3.5 to 5.5.

19. Sodium citrate : Sodium citrate (trisodium citrate, C 6 H 5 Na 3 O 7 , MW 258.07, anhydrous; dihydrate, MW 294.10) occurs as colorless crystals or as a white, crystalline powder. The hydrous form is freely soluble in water (1 g in 1.5 mL), highly soluble in boiling water (1 g in 0.6 mL), and insoluble in alcohol. Sodium citrate is stable and can be sterilized by autoclaving. When sodium citrate is stored in a glass container for a period of time, separation of small, solid particles may occur. The bulk material should be stored in an airtight container in a cool, dry place. Each gram of dihydrate represents approximately 10.2 mmol sodium and 3.4 mmol citrate; each gram of anhydrous represents about 11.6 mmol sodium and 3.9 mmol citrate.

20. Sodium bisulfite : Sodium bisulfite (sodium hydrogen sulfite, NaHSO 3 , MW 104.07) occurs as a white, crystalline powder. It is soluble 1 in 3.5 parts of water and in 70 parts of 95% alcohol. Most substances sold as sodium bisulfite contain significant but variable amounts of sodium metabisulfite; sodium metabisulfite is less hygroscopic and more stable during storage and shipment. Sodium bisulfite generally is used as an antioxidant in solutions of intermediate pH

21. Sulfuric acid : Sulfuric acid (oil of vitriol, H 2 SO 4 , MW 98.08) occurs as a clear, colorless, oily liquid that is miscible with water and alcohol with the generation of heat. It is highly caustic and corrosive. Sulfuric acid has an SG of about 1.84 and is used as an acidifying agent. It is hygroscopic and contains not less than 95% and not more than 98% of H 2 SO 4  by weight, the remainder being water. Sulfuric acid is a powerful oxidizer; it may ignite or explode upon contact with numerous materials.

22. Uses : Amikacin 250mg Injection is an antibiotic used to  prevent or treat a wide variety of bacterial infections . These may include infections of the urinary tract, bones, and joints, lungs ( eg . pneumonia), brain, blood, among others. It is also used in hospitalized patients to prevent infections.

23. Side effects of Amikacin Injection : Increased blood urea. Injection site reactions (pain, swelling, redness).

24. Reference : 1.)   U.S. Pharmacopeia 34/NF 29 . Rockville, MD: U.S. Pharmacopeial Convention, Inc; 2011:330-336,336-373,1009,2533-2536. 2.) McEvoy GK, ed.  ASHP Drug Information 2011 . Bethesda, MD: American Society of Health-Systems Pharmacists; 2011:2620-2623. 3.) Niazi SK.  Handbook of Pharmaceutical Manufacturing Formulations, Volume 6—Sterile Products . Boca Raton, FL: CRC Press; 2004:73. 4.) USP Pharmacists’ Pharmacopeia . 2nd ed. Rockville, MD: US Pharmacopeial Convention, Inc; 2008:775-779,779-831,1463.