Types of Parenteral Formulation

Parenterals

1. TYPES OF PARENTERAL FORMULATIONS PRESENTED BY - NIDHI BANSAL M.PHARMACY

2. PARENTERAL PRODUCTS . Parenteral products are intended for use by injection under or through one or more layers of the skin or mucous membranes. They must be free from microbial contamination and from toxic components as well as possess an exceptionally high level of purity. All components and all processes involved in the preparation of these products must be selected and designed to eliminate contamination of all types, whether of physical,chemical or microbiological origin.

3. PRODUCT DEVELOPMENT The final sterile product must give a therapeutic effect in a patient. The effect of physical and chemical factors on preparation be minimum. The preferred preparation for neural use are solution preparation for intramuscular, subcutaneous, intradermal use can be solutions,suspensions or emulsions. The chemical and physical properties of a drug must be analyzed for knowledge about onset of action,interaction with excipients and stability. The solvent system should produce no tissue irritation thus be free from any traces.

4. GENERAL REQUIREMENTS STABILITY STERILITY FREE FROM PYROGENS AND TOXINS ISOTONIC TO BLOOD CHEMICAL PURITY FREE FORM FOREIGN PARTICLES

5. TYPES OF PARENTERAL ROUTES INTRAVENOUS INTRAMUSCULAR SUBCUTANEOUS INTRA-ARTERIAL INJECTION INTRACARDIAC INJECTION INTRATHECAL INJECTION PERIDUAL INJECTION INTRA-ARTICULAR INJECTION INTRACEREBRAL INJECTION INTRAOCULAR INTRA-ABDOMINAL

6. Fast- acting route because the drug goes directly into the bloodstream. Often used in the emergency department and in critical care areas. Commonly used - for fluid and electrolyte replacement - to provide necessary nutrition to the patient who is critically ill Intravenous injections are administered at a 15 to 20 degree angle. Volume NMT 1 litre. Example - Dextrose, Mannitol INTRAVENOUS INJECTIONS .

7. INTRAMUSCULAR INJECTIONS In adults, IM injections are given into upper, outer portion of the gluteus maximus. For children and some adults IM injections are given into the deltoid muscles of the shoulders. Typical needle is 22-25 gauge 1/2 to 1 inch needle. IM injections are administered at a 90 degree angle. - volume limited to less than 2 ml Example- Cephalosporin, Morphine, Haloperidol . .

8. SUBCUTANEOUS Administer medications below the skin into the subcutaneous fat. Often have a longer onset of action and a longer duration of action compared with IM or IV injection. Given at a 45-degree angle - 25-or 26 gauge needle , 3/8 to 5/8 inch length Not more than 1 ml should be injected into the site to avoid pressure on sensory nerves causing pain and discomfort. Example - Insulin, Morphine

9. . INTRA-ARTERIAL INJECTION Drug administered within or into the artery or arteries. Example- Anticancer agent for drug targeting to a particular organ. INTRACARDIAC INJECTION These are given directly into the heart muscle or ventricles at the time of emergency only. Example- Antiarrthymatic drugs, Quinidine,Propanolol.

10. . INTRATHECAL INJECTION These are given into the subachonoid space that surround the spinal cord.This route is used for spinal anesthesia. PERIDUAL INJECTION These are given between the dura matter and inner aspect of vertebra. Used for given spinal anesthesia.

11. . INTRA-ARTICULAR INJECTION These are given into the articulating ends of bones in the joints. Injections of antibiotics and corticosteriods are administered in inflammed jointed cavities by experts. INTRACEREBRAL INJECTION Drugs are introduced or administered into the cerebrum. Example- Adrenaline, Amphetamine

12. . INTRAOCULAR Drugs are administered by entering the eyeball and around the eyes. Example- Avastin, Carbacol INTRA-ABDOMINAL Drugs are admininstered through the cavity of the abdomen. And this is one given to intraperitoneal. Example- Dialysis soltion. Heparin

13. COMPONENTS OF PARENTERAL PREPARATION VEHICLE Aqueous Vehicle - water for injection bacteriostatic water for injection water miscible vehicles tested for solid content, pyrogens and ions 2. Non- Aqueous Vehicle- used in combination with water: dioxolanes, dimethyl acetamide N- (2-hydroxyethyl) - lactamide, butylene glycol, glycerin and ethyl alcohol. water immmicible solvents: fixed oils (peanut oil, cotton seed oil)ethyl oleate, isopropyl myristate, benzyl benzoate.

14. ADDED SUBSTANCES ANTIBACTERIAL AGENTS : added to multiple doses injection to prevent microbial growth. For eg-phenol and cresol (0.05%) BUFFERS : it maintains the pH of the solution and prevents chemical degradation. For eg- Acetate and citrate buffer ANTI-OXIDANTS : to protect the formulation for oxidation. Two types of anti oxidants. Reducing Agents : eg - ascorbic acid, thiourea Blocking Agents : eg- tocopherol SURFACTANTS : added to solubilise the active ingredient.For eg- sorbitol, monooleate TONOCITY AGENTS : it is needed to maintain the formulation to be isotonic with the body fluids to avoid the destruction of ed blood cells, irritation and tissue damage. For eg- NaCl, KCl, Dextrose CHELATING AGENTS : to trace elements that catalyse oxidative degeneration. For eg- EDTA

15. CLASSIFICATION OF PREPARATION Small Volume Parenteral Large Volume Parenteral An injection that is packed in containers labelled as containing 100 ml or less An injection that is packed in containers labelled as containing 101ml - 1000ml Single or multiple use Single use Preservatives are used. Preservatives are not used Administered through various parenteral routes. Administered through IV infusion technique

16. Small Volume Parenteral Large Volume Parenteral

17. TYPES OF LARGE VOLUME PARENTERALS Hyper alimentation solution Administration of nutrients to the patient who is unable to take them orally. Eg mixture of dextrose, amino acids, lipids, vitamins etc. Cardioplegic solution Used in heart surgery to prevent injury in myocardium. Peritoneal Dialysis Infused into abdominal cavity Remove toxic substances from the body Irrigation solution To irrigate flush and aid body cavities and wounds. Eg- saline solution

18. TYPES OF PARENTERAL PREPARATIONS BASED ON MODE OF DELIVERY INJECTIONS- Injections are sterile,pyrogen freesolutions or dispersions (emulsions or susensions) of one or more active ingredients in a suitable vehicle. Single- dose injections : They should not contain antimicrobials preservatives unless justified and authorized. Injections with antimicrobial preservative must not be administered intracisternally, intrathecally, epidurally or by any route giing access to the cerebrospinal fluid, or intraocularly. Multi-dose preparations : Multidose preparations contain a suitable antimicrobial preservative in appropriate concentrations except in cases where the preparations themselves have adequate antimicrobial properites. Multidose preparation should normally not exceed 30 mL.

19. INTRAVENOUS INFUSIONS Intravenous infusions are sterile, pyrogen-free aqueous solutions or emulsions with water as continous phase, usually prepared to be isotonic. They are intended for administerd in large volumes (usually more than 100 mL) and od not contain any antimicrobial preservatives. On visual inspection emusions for intravenous injection should show no evidence of phase separation.

20. POWDERS FOR INJECTIONS Powders for injections are sterile, pyrogen-free solid substances (including freeze-dried materials), distributed in their final containers and which, when the prescribed volume of the appropriate sterile liquid is added, rapidly form either clear and practically particle - free solutions or uniform suspensions. After dissolution or suspension,comply with the requirements for injections or intravenous infusions, as appropriate .

21. IMPLANTS Implants are sterile solid preparations containing one or more active ingredients. They are of a size and shape suitable of parenteral implantation and provide release of the active ingredients over an extended period of time. They are presented in individual sterile containers. All requirements for these specialized dosage forms are given in the individual monographs.

22. CLASSIFICATION BASED ON TYPE OF FORMULATION SOLUTION SUSPENSIONS INJECTABLE EMULSIONS FREEZE DRY POWDERS

23. SOLUTIONS A solution is a liquid preparation that contains one or more soluble chemical substances dissolved in a specified solvent. Large quantity component- solvent , small quantity component- solute . Aqueous system: Compound dissolved - ionisable electrolytesand organic substances like aldehydes, alcohols, ketones and amines. Compound undissolved- Non Polar compounds Non - Aqueous system: These are anhydrous, nonpolar vehicleslike fixed oils.

24. IDEAL PROPERTIES OF SOLVENTS SOLUBILITY- Therapeutically active compounds of parenteral route range in properties frompolar to non polar thus solvents with complementary properties are employed. Example- Digitalis glycosided solubilize in 40% ethanol in water solution. TOXICITY- solvent be of minimum toxicity to body tissue. Example - Testosterone is soluble in ether but cannot be used alone due to its high irritant nature. pH- Stability is markedly affected by pH of solution. Example- Epinephrine in parenteral solution - stable at pH < 3 Atropine sulphate is stable at pH 3-4. DEGRADATION REACTION - water is prone to degradative reactions such as hydrolysis, oxidation etc. thus appropriate measures can be employed.

25. SUSPENSIONS Solid content- 0.5% to 5.0% (30% for antibiotic preparations) Administered usually by subcutaneous or intramuscular route Partcile size less than 5 micrometre (uniform particle size is necessary) Formulation of Suspensions: Sterile vehicle and powder - aseptic combination Stabilizing Agents- Surface Active Agents- Polysorbate 80,Lecithin Protective Colloid - Sodium CMC, Acacia ,Gelatin Electrolytes- Mono sodium citrate

26. EMULSIONS An emulsion is a heterogeneous dispersion of immiscible liquid in another,droplet size (1-5 microns) The density difference of the two phases is kept as low as possible. Emulsifiers like lecithin, oxyethylene-oxypropylene polymer, gelatin, methyl cellulose have been employed. Parenteral emulsion are rare because it is necessary and difficult to achieve stable droplet of less than 1micron to prevent emboli in blood vessels, which is difficult to prepare for such a preparation. Very limited selection of emulsifier and stabilizers is there to choose from. Administered through : IV, IM route Example- Emulsion of natural vitamin K1 has been stabilized with lecithin.

27. DRY POWDERS It is formulation of lypophilized or freeze- dried powders that must be reconstituted with some suitable solvent to make a liquid formulation before being withdrawn form the vial. To overcome the instrinsic instability of the drug in the aqueous medium this formulation is employed. The solid residue after freeze drying must have following characteristics: Uniform color and texture, solid matrix to maintain original volume , sufficient strength to prevent crumbling during storage. The nature and amount of solids in solution determine: Eutectic Temperature, Sub zero temperature (at which frozen material will melt- determines storage temperature.), rate of thermal and vapour transfer during drying. Salts used as solids: mono and dibasic sodium phosphates, NaCl, mannitol, sorbitol, sucrose and gelatin.

28. CONCLUSION The parenteral formulations are one of the most essential drugs systems in pharmaceutical industry. Due to their direct administration in body cavities their sterlity and formulation stablity is must follow criterion. Depending upon their administeration, they can be of varous types like injections, implants infusions, etc. All the parenteral products must be prepared in aseptic conditions. The physical and chemical properties of all components of parenteral preparations are thoroughly studied for any incompatibilities if possible.

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