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Parenteral preparations

lvp, svp, formulation of parenterals,water for injection,etc

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Parenteral preparations

  1. 1. 1
  3. 3. 3 The term derived from Greek word ‛Para’ outside & ‛Enterone’ intestine. Parenterals are sterile solutions or suspension of drug in aqueous or oily vehicle. Parenteral drugs are administered directly in to the veins, muscles or under the skin , or more specialized tissues such as spinal cord. Term parenteral used for any drug/fluid whose delivery doesn’t utilize the alimentary canal for entering in to the body tissues.
  4. 4. 4 • Stability • Sterility • Free from pyrogens & toxins • Free from foreign particles • Isotonic • Chemical purity
  5. 5. 5 PARENTERAL ROUTES The term parenteral literally means to avoid the gut (gastrointestinal tract) and refers to any route of administration outside of or beside the alimentary tract. Thus, parenterals are injectable drugs that enter the body directly and are not required to be absorbed in the gastrointestinal tract before they show their effect. Parenteral routes of administration usually have a more rapid onset of action than other routes of administration.
  6. 6. 6 1. Intravenous 2. Intramuscular 3. Subcutaneous 4. intradermal 5. Intra-arterial 6. Intracardiac 7. Intrathecal 8. Intracisternal 9. Peridural 10.Intraarticular 11.Intracerebral PARENTERAL ROUTES
  7. 7. Intravenous • The injection of a drug directly into the patient's veins, resulting in the most rapid onset of action. 7
  8. 8. 8 Intradermal The drug is injected into the top few layers of the skin. Ideally, the drug is placed within the dermis. Used for diagnostic agents. Subcutaneous The injection of the drug under the skin into the fatty layer, but not into the muscle. Absorption of the drug is rapid. Eg; insulin
  9. 9. 9 Intramuscular Drugs are injected deeply into muscle tissue. If the drug is in aqueous (water) solution, absorption is rapid. However, if the drug is in an oily liquid or in the form of a suspension, it can prolong the release of the drug.
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  12. 12. 12 Useful for patients who cannot take drugs orally Rapid onset of action Useful for emergency situations Providing sustained drug delivery (implants, im depot inj) Avoid first pass metabolism Can inject drug directly in to a tissue (target drug delivery) Useful for delivering fluids, electrolytes, or nutrients (TPN) Can be done in hospitals, ambulatory infusion centers and home health care centers Complete bioavailability.
  13. 13. 13 Pain on injection Difficult to reverse an administered drug’s effect. Sensitivity or allergic reaction at the site of injection. Requires strict control of sterility & non pyrogenicity than other formulation. Trained person is required. Require specialized equipment, devices, and techniques to prepare and administer drugs. More expensive and costly to produce.
  14. 14. 14 1. Small volume parenterals (SVP) 2. Large volume parenterals (LVP)
  15. 15. 15 USP defn: An injection that is packed in containers labeled as containing 100 ml or less. Defn: LVP are parenterals designed to provide :- Fluid Calories (dextrose solution ) Electrolytes Combenation of these Volume 101- 1000 ml
  16. 16. 16 parameter SVP LVP volume 100 ml or less 101-1000 ml Routes IV, IM & SC IV- LVP & non IV- LVP Dosage unit Single or multiple Single preservative Used Not used Buffers Used Not used Formulation Soln, emulsion,suspension. Soln & o/w nutrient emulsion Isotonicity Not essential must Pyrogenicity Not essential must use Therapeutic & diagnostic Nutrition,detoxification, And during surgery
  17. 17. 17 AQUEOUS VEHICLE : WATER FOR INJECTION (WFI) USP : Highly purified water used as a vehicle for injective preparations which will be subsequently sterilized. USP requirement include not more than 10 parts per million of total solids. pH of 5.0 – 7.0 . WFI may be prepared by either distillation or reverse osmosis.  Stored in chemically resistant tank.
  18. 18. 18 BACTERIOSTATIC WATER FOR INJECTION This type of water used for making parenteral solutions prepared under aseptic conditions and not terminally sterilized. Need to meet USP sterility test. It can contain an added bacteriostatic agent when in containers of 30 ml or less.
  19. 19. 19 STERILE WATER FOR INJECTION SWFI containing one or more suitable bacteriostatic agent.  multiple – dose containers not exceeding 30 ml. They are permitted to contain higher levels of solid than WFI because of possible leaching. Used for washing wounds , surgical incisions, or body tissues.
  20. 20. 20 WATER MISCIBLE VEHICLES The number of solvents that are miscible with water has been used as a portion of a vehicle. Primarily to affect solubility of drugs and to reduce hydrolysis. Example: Ethyl alcohol, Liquid propelene glycol Glycerine Ethyl alcohol used in the case of cardiac glycoside.
  21. 21. 21 NON – AQUEOUS VEHICLES Fixed oils (vegitable origin, liquid, and rancid resistance ,unsaturated, free fatty acid content ) Peanut oil Corn oil Cotton seed oil (depo-testosterone) Sesame oil Soyabean oil Ethyl oleate Isopropyl myristate.
  22. 22. 22 ANTIBACTERIAL AGENTS These are added in multiple dose containers. To prevent microorganism growth Limitted concenteration of agents are used. Phenyl mercuric nitrate and thiomersol 0.01%. Benzethonium chloride & benzalkonium chloride 0.01%. Phenol & cresol 0.05%. Chlorobutanol 0.05%.
  23. 23. 23 BUFFERS Added to maintain pH. To stabilize a solution from chemical degradation. Citrate and acetate buffer. Sodium benzoate and benzoic acid Sodium tartarate and tartaric acid Phosphate buffer.
  24. 24. 24 ANTIOXIDENT To protect the formulation from oxidation Two types 1. Reducing agents Ascorbic acid Sodium bisulfite 0.01% Thiourea 2.Blocking agents Tocopherol
  25. 25. 25 SURFACTANTS  Solubilise the active ingredient Polyoxythylene sorbitan monooleate & Sorbitan monooleate TONICITY AGENTS Need isotonic solution to avoid destruction of red blood cells, irritation, and tissue damage  More important for large volumes, rapidly administered, and extravascular injections  Reduces the pain on injection NaCl & KCl Dextrose Mannitol & Sorbitol Effect of different solutions on blood cells
  26. 26. CHELATING AGENTS  To remove trace elements that catalyse oxidative degeneration Ethelene diamine tetra acetic acid 26 CO-SOLVENT  Improve solubility  Prevent potential for hydrolysis
  27. 27. 27 BULKING AGENTS  For freeze dried preparations(solids) Mannitol Lactose ,sucrose Dextran . SUSPENDING AGENTS CMC, Methyl cellulose, Gelatin Sorbitol . EMULSIFYING AGENTS Lecithin Polysorbate 80
  28. 28.  A clear and colorless liquid; odorless.  Water for injections is pyrogen -free.  It contains no added substance.  Water for injections is obtained from potable or Purified water by distillation in an apparatus.  The distillate is collected and stored in conditions designed to prevent growth of microorganisms and to avoid any other contamination. 28
  29. 29. • The source water usually must be pretreated by one or a combination of following treatment: • Chemical softening, filtration, deionization, carbon absorption, or reverse osmosis purification. • There are three types of distillation still to produce water for injection. 1. Compression distillation 2. Multiple-effect still 3. Reverse osmosis 29
  30. 30. • Vapor compression still is primarily designed for the production of large volumes of high purity distillate with low consumption of energy and water. • Vapor compression processes produce water 5 to 10 times more cost effectively than multiple effect distillers. • PROCEDURE: • Step 1: In a Vapor Compression still, the boiling process begins with both heating elements turned on. As the water in the boiling chamber reaches near boiling temperatures, the compressor turns on. 30
  31. 31. • Step 2: In the compressor, the steam is pressurized, which raises the steam's temperature before it is routed through a special heat exchanger located inside the boiling chamber. • Step 3: The pressurized steam gives off its heat to the tap water inside the boiling chamber, causing this water to boil, which creates more steam. 31
  32. 32. • Step 4: While the pressurized steam is giving up its latent heat, the steam will condense. One of the heating elements will cycle on and off periodically as needed. • Step 5: At this stage, the condensed steam is considered distilled water but is still very hot--only slightly cooler than boiling temperature. 32
  34. 34. • It is also designed to conserve energy and water usage. • In principle, a series of single effect stills running at different pressures. • A series up to seven effect may be used, with the first effect operated at a highest pressure and the last effect at atmospheric pressure. • The capacity of still can be increased by adding effects. The quantity of distillate will also be affected by inlet steam pressure 34
  35. 35. PRODEDURE:  Steam from the external source is used in the first effect to generate steam under pressure from feed water, it is used as a power source for second effect.  The steam used to drive the second effect condenses as it gives up its heat of vaporization and forms a distillate.  The process continues until the last effect, when the steam is at atmospheric pressure and must be condensed in a heat exchanger. 35
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  37. 37. REVERSE OSMOSIS: • The natural process of selective permeation of molecule through a semi-permeable membrane separate two aqueous solutions of different concentration is reversed. • Pressure, usually between 200 to 400 psig, is applied to overcome osmotic pressure and force pure water to penetrate through the membrane. • Membrane composed of cellulose esters or polyamides. 37
  38. 38. 38 •. It provide effective rejection of contaminant molecules in raw water. •Sodium chloride is most difficult to remove. •Passage through two membranes in series is sometimes used to increase the efficiency of removal of small molecules. • ex. Aqua chem , Finn-aqua, Meco , Milipore etc.
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  40. 40. STORAGE AND DISTRIBUTION • Distillate is collected in holding tanks for subsequent use. • USP permit the storage of WFI at room temp. maximum for only about 24hr. • When the water can not be used at 80º c , heat exchangers must be installed to reduce the temperature at the point of use. 40
  41. 41. 41 LARGE VOLUME PARENTERALS REQUIREMENTS Sterile, non pyrogenic, free from particulate matter Volume 101- 1000ml Single dose unit No preservative Clear solution except fat emulsion Isotonic, but hypertonic also administered in TPN
  43. 43. 43 HYPERALIMENTATION SOLUTION Admin. Of large amount of nutrients to patients who unable to take food orally. Formulation: mix. Of dextrose, amino acids , lipids, electrolytes,& vitamines.
  44. 44. 44 TOTAL PARENTERAL NUTRITION Def. :A method of feeding patients by infusing a mixture of all necessary nutrients into the circulatory system, thus bypassing the GIT. CONTENT SOURCES 1. calories Dextrose 2. Nitrogen Crystalline amino acids 3. Electrlyte Na , K, Cl , Po4, 4. Vitamines Water soluble & Fat soluble 5. Elements Traces of Zn, Cu, Mn, Cr
  45. 45. 45 2. CARDIOLPLEGIC SOLUTIONS Are LVP used in heart surgery to prevent injury to myocardium during reperfusion, as well as to maintain bloodless operating field. Maintains the diastolic arrest. Administerd in cold form. Slightly alkaline to compensate metabolic acidosis, Hypertonic USE: To minimize reperfusion injury resulting from tissue edema.
  46. 46. 46 3. PERITONEAL DIALYSIS SOLUTION  Infused continuously into abdominal cavity, bathing peritonium & are then continously withdrawn. USE Removal of toxic substances from body. To aid & accelerate excretion normal. To treat acute renal insufficiency.
  47. 47. 47 4. IRRIGATING SOLUTIONS To irrigate ,flush, & aid in cleaning body activities & wounds. Certain IV solution ( normal saline ) may be used as irrigating solution , but solution designed as irrigating soln should not be used parenterally. Use: Treatment of serious wounds infused in to blood stream.
  48. 48. 4848 EXAMPLES OF LVP
  49. 49. 49 Small volume parenterals • Small volume intravenous injection is applied to an injection that is packaged in containers labelled as containing 100 ml or less. 49 1. Solution: 2. Suspension: 3. Emulsion: 4. Dry powders:
  50. 50. solutions • Typically used for delivering medications at a controlled infusion rate • Most commonly solutions of 5% dextrose, normal saline, 45% normal saline, or 5% dextrose with normal saline. • Dextrose contributes glucose to meet energy needs and saline contributes sodium, an electrolyte that maintains fluid balance and cellular functions.
  51. 51. SUSPENSION • They should be sterile, pyrogen free, stable, re‐suspendable, syringeable, injectable, isotonic & non‐irritating. • They are usually administered by either subcutaneous (S.C.) or intramuscular (I.M.) route. • These suspensions usually contain between 0.5% and 5.0% solids & should have particle size less than 5 micrometer for I.M. or S.C. administration. • Certain antibiotic preparations (For example procaine Penicillin G) may contain up to 30% solids 51
  52. 52. • Advantages of Parental suspension • It is better for the therapeutic use of drugs that are insoluble in convention solvents. • In this dosage from there is increased resistance to hydrolysis & oxidation as drug is present in the solid from. • Formulation of controlled released drug is possible in this dosage form. • There is elimination of hepatic first pass effect. 52
  53. 53. Injectable Emulsion- • An emulsion is a heterogenous dispersion of one immiscible liquid in another. • This inherently unstable system is made possible through the use of an emulsifying agent, which prevent coalescence of the dispersed droplet. • Parenteral emulsion are rare because it is necessary (and difficult) to achieve stable droplet of less than 1 micron meter to prevent emboli in blood vessels and it is not usually necessary to achieve an emulsion for drug administration. 53
  54. 54. 54 Dry Powders Purpose: To overcome the intrinsic instability of the drug, be reconstitute before use. • Production Method: – Freeze-drying –Aseptic crystallization and dry powder filling – Spray-drying
  55. 55. • Pharmaceutical product development by N K Jain. • Theory and practice of industrial pharmacy by Lachman and Leiberman. • www. 55 REFERENCE
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