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Parentrals

A detailed description about parentrals, route of administration, preformulation, sterilization, preparation and evaluation.

Parentrals

  1. 1. PARENTERALS PRESENTED BY P.KALYANI (11AB1R0075) UNDER THE GUIDANCE OF Mrs K. PALLAVI M.Pharm Asst . Professor VIGNAN PHARMACY COLLEGE Affiliated to JNTU Kakinada Approved by AICTE, PCI Vadlamudi, Guntvuigrna nD phisartm. aAcy ncodllehgerapradesh-522213. 1
  2. 2. CONTENTS • INTRODUCTION • ROUTE OF ADMINISTRATION • GENERAL REQUIRMENTS • PRE-FORMULATION • ADJUSTMENT OF TONICITY METHODS • STERILIZATION • FORMULATION OF PARENTERALS • PACKAGING • EVALUATION OF PARENTERALS. vignan pharmacy college 2
  3. 3. INTRODUCTION • The term of parenteral is derived from Greek word para meaning beside and enteron meaning the intestine. • Thus parenterals administration should include the administration of drug by any route other than intestine. • Parenteral products are considered to be those sterile drugs, solutions, emulsions, suspensions. vignan pharmacy college 3
  4. 4. DEFINITION Parenterals are sterile preparations intended for administration under or through one or more layers of skin or mucous membranes. vignan pharmacy college 4
  5. 5. ADVANTAGES • The parenterals are administration of unconscious patients. • Who can not take oral administration. • They are free from pyrogen. • Low toxicity as compared to solid dosage forms. • 100% bioavailability. • No chance of missing dose. vignan pharmacy college 5
  6. 6. DISADVANTAGES • Requirement of aseptic technique in production compounding and handling of products. • Requirement of trained personnel for administration. • Real or psychological pain associated with the injection. • Highly risky if any mistake at happens any point. • High cost as compared to solid dosage forms. vignan pharmacy college 6
  7. 7. ROUTE OF ADMINISTRATION Intravenous Intramuscular Subcutaneous Intradermal Other routes vignan pharmacy college 7
  8. 8. VARIOUS TYPES OF ROUTE OF ADMINISTRATION vignan pharmacy college 8
  9. 9. vignan pharmacy college 9
  10. 10. vignan pharmacy college 10
  11. 11. vignan pharmacy college 11 Not more than
  12. 12. Intra arterial injection vignan pharmacy college 12
  13. 13. vignan pharmacy college 13 Intra cisternal injection
  14. 14. GENERAL REQUIRMENTS Vehicle General requirements Additives Containers and emulsifying agents Tonicity contributors vignan pharmacy college 14
  15. 15. VEHICLE • Water for injection is the vehicle of first choice. It should be free from ions and carbohydrates. • No bacterial contamination. • Bacteriostatic water for injection is sterile water for injection containing one or more bacteriostatic agents. • Some co-solvents are used from preparation. • Water missible co solvent include in ethyalcohol,glycerin and propylenglycol,polyethyleneglycol. vignan pharmacy college 15
  16. 16. • In addition of solutes should be free from microbial contamination. • Using additives various types. VEHICLE • Stabilizers ensure the stability of the drug compound in the preparation. • Eg: chelating agent like EDTA. STABILIZERS WETTING, SUSPENDING AND EMULSIFYING AGENT vignan pharmacy college 16 • Wetting agent to maintain the particle size. • Eg: Tween80,sorbital,trioleate,etc… • Suspending agent is acacia, gelatin etc….
  17. 17. •Formulations must be maintain the intended Ph. •Eg:Acetone,citrates,phosphates etc… BUFFERING AGENTS • Oxygen sensitive drugs so as to avoid oxidative degradation. • Eg:Sodiumbisulphate,formaldehyde, acetone,thiourea and EDTA. ANTIOXIDANTS • It is used for prevention of microbes in multiple packaging. • Eg:phenol or chlorobutanol, etc… ANTIMICROBIAL AGENTS vignan pharmacy college 17
  18. 18. TONICITY CONTRIBUTORS Eg: sodium chloride, and borax etc… Determining the freezing point of the solutions. Parenteral solutions are required to be isotonic with blood serum or other body fluids. vignan pharmacy college 18
  19. 19. CONTAINERS AND CLOSURES • Any container for parenteral products should maintain the integrity of the product. • Sterile and pyrogen free. • Should also attractive. • Should not react with the products. • Glass, plastic, rubber materials used type-1 glass mainly used. • Plastic used in polyethylene, polypropylene. vignan pharmacy college 19
  20. 20. PREFORMULATION vignan pharmacy college 20
  21. 21. PREFORMULATION • Preformulation involves the determination of both physical and chemical properties of drug with the goal producing a new drug which is safe stable and efficacious. • The establish the physicochemical properties of new drug moiety. • Determine the kinetic profile of new drug. • Preformulation studies are of various types: Physicochemical properties of new drug substance. Stability testing. Mechanism of drug degradation. Testing for packaging material vignan pharmacy college 21
  22. 22. Physicochemical properties of new drugs PRE-FORMULATION Mechanism of drug degradation Test for packaging material Stability test vignan pharmacy college 22
  23. 23. • The first and most important step in preformulation is determine the molecule structure and weight. MOLECULAR STRUCTURE AND WEIGHT • Appearance of colourchange is indicative of physicochemical instability which may decrease the shelf life of the product. COLOUR • The drug may undergo physical or chemical changes due to variations of temperature which may be associate with loss or gain. The change analyzed by DTA and DSC. THERMAL ANALYSIS vignan pharmacy college 23
  24. 24. SOLUBILITY • A clear solution for injectable that are to be administered either infusion or via i.m route mainly depends on solubility. • Solubility of drug substances can be determined by spectrophotometric method or from Ph profile. • Non aqueous solvents like ethyl alcohol, glycerin, polyethylene glycol. PARTITION CO-EFFICIENT • It is used to determine the rate and extent of drug absorption. • They are explained by equation: P=Co/Cw vignan pharmacy college 24
  25. 25. TEST FOR STABILITY LIGHT STABILITY • Drug solution placed in the petriplate and glass ampoules respectively. • Drug substance placed in light resistant container such as carbon box which act as controller. • The samples are placed and maintain lighting condition such as 500 foot candles for a period of 4 weeks. • consider light extremely any changes discolouration, precipitation, decomposition observe in the sample to consider light sensitive and require light protection in both solid and liquid form. vignan pharmacy college 25
  26. 26. MECHANISM OF DRUG DEGRADATION • It is the most common reaction which responsible for the degradation of compounds.Eg:sodium Phenobarbital etc. HYDROLYSIS • Oxidation may lead to discolouration of the parenteral solution. • Eg:ascorbic acid, adrenaline etc. OXIDATION REACTION • This reaction is commonly observed in compounds containing carboxylic acid functional group DECORBOXYLATION vignan pharmacy college 26
  27. 27. TESTING FOR PACKAGING COMPONENTS GLASS • Powdered glass test. • Water attack test. PLASTIC • Leakage test • Collapsibility test • Clarity of aqueous test • transparency RUBBER • Penetrability • Fragmentation • Self sealbility test • Extractive test vignan pharmacy college 27
  28. 28. ADJUSTMENT OF TONICITY METHODS CRYSCOPIC METHOD TONICITY METHODS WHITE-VINCET METHOD MOLECULAR CONCENTRATION NACL EQUIVALENT METHOD vignan pharmacy college 28
  29. 29. PRECAUTIONS FOR ASEPTIC WORK • The parenteral products are free from microbial contamination following precautions should be observed in aseptic work. • Whenever possible a non-touch technique should be used. • Air disturbance should be maintained. • Only trained person should be perform aseptic work. • Whenever contamination is detected the sources should be removed. vignan pharmacy college 29
  30. 30. Solutions sterilized by filtration are to be filled under aseptic conditions. Filling consist of a quantity of the product measuring by precision. Modern days automatic high speed filling can fill up to 300 or more container per min. FILLING vignan pharmacy college 30
  31. 31. Prevent the contamination. Vials and bottles are sealed by close and open with a closures. Variety of automated sealing devices are available today. SEALING vignan pharmacy college 31
  32. 32. vignan pharmacy college 32 STERILIZATION Heat Sterilization Filtration Sterilization Radiation Sterilization Gaseous Sterilization Moist heat Dry heat Non ionizing radiations Ionization radiation Hot air oven Incineration
  33. 33. STERILIZATION STERILIZATION PROCESS BIOLOGICAL INDICATION Moist heat sterilization Spores of bacillus stearothermophillus are killed. Dry heat sterilization Spores of bacillus purmilus. Ionization radiation sterilization Spores of bacillus pumilus bacillus subtilis. Gaseous sterilization Spores of bacillus subtilis. Filtration sterilization Spores of serratia marcescens Spores of brevundimonas diminuta vignan pharmacy college 33
  34. 34. PARENTERAL PREPARATION AREA vignan pharmacy college 34
  35. 35. vignan pharmacy college 35
  36. 36. PRODUCTION OF PARENTERALS  They are various types of parenterals:  Powder parenterals for injection :-Eg-cefuroxine for injection  Colloidal solution :-Eg-irondextran  Injectable suspension :-Eg-methyl prednisolone acetate  Oily injectable solutions :-dimercaprol injection vignan pharmacy college 36
  37. 37. PRODUCTION OF PARENTERALS 37 vignan pharmacy college  General steps involved Cleaning Preparation of bulk production Filtration Filling of solution in ampoules or vials sealing Sterilization and test quality control.
  38. 38. SMALL VOLUME PARENTRALS PREPARATION  Small volume of parenterals include ampoules of 1ml, 2ml,3ml up to 20ml and vials of 1ml up to 3oml.  They are administered by various routes  They most widely used small volume parenterals are various insulin preparations used for treatment of diabetes mellitus.  EXAMPLES:-DIGOXIN-Solution it is administered i.v it is used for cardiotonic.  Procaine pencilinG :- it is used for treatment of bacterial infection. vignan pharmacy college 38
  39. 39. LARGE VOLUME PARENTRALS PREPARATION • Large volume of parenterals contain 100ml and more of injection solution they are general administered i.v route. ELECTROLYTES • Sodium chloride and potassium chloride solutions NON-ELECTROLYTES • Dextrose,mannitol solution. • Large volume of parenterals are provides nutrition. • Loss of water diarrhea or vomiting in case used. • When they are unable to consume oral nutrition for longer periods (3-6days). vignan pharmacy college 39
  40. 40. POWDER PARENTERALS • Dry powders are available in the market they are soluble in water for injection or in other sterile solvent just prior to use. • Powder Parenterals are suitable for certain formulations which degrade by hydrolysis. EXAMPLES • Penicillin,ampicillin,amoxycillin,etc…. vignan pharmacy college 40
  41. 41. VOLUME OF INJECTION VOLUMES(ML) EXCESS VOLUMES (MOBILE PHASE) EXCESS VOLUME(VISCOUS PHASE) 0.5 0.10 0.12 1.0 0.10 0.15 2.0 0.15 0.25 5.0 0.30 0.50 10.0 0.50 0.70 20.0 0.60 0.90 50.01 2% 3% vignan pharmacy college 41
  42. 42. vignan pharmacy college 42
  43. 43. Air control FACILITIES Environmental control Surface disinfection Personnel traffic control vignan pharmacy college 43
  44. 44. HEPA FILTER ◊ Hepa filters can remove at least 99.97% of air bone particals 0.3 mm in diameter. ◊ These are composed of a mat of randomly arranged fibers. ◊ The air space between hepa filter fibers is much greater than 0.3mm. ◊ Smaller pollutants and particles are mainly trapped by one of the following…. - Interception - Impaction - Diffusion vignan pharmacy college 44
  45. 45. TYPES OF AIR CONTROL SYSTEMS S.NO CLASS DESCRIPTION PREPARATION AREA A Class 100 Particle count in air is not more than 100 per cubic foot of 0.5 μ and particle size. Sterile and aseptic area. B Class 1000 Particle count in air is Not more than 1000 per cubic foot of 0.5μ. Manufacturing area. C Class10,000 Particle count in air is not more than 10,000 per cubic foot of 0.5μ and particle size Package and storage area vignan pharmacy college 45
  46. 46. PACKAGING GLASS PLASTIC RUBBER vignan pharmacy college 46
  47. 47. GLASS • Glass materials are no water permeation and glass permeation not react with products. • Physical property is optically clear rigid so mainly glass material used. PLASTIC • Plastic closures are used for packaging of parenterals • Examples:-ampoules(single dose) ,vials(multiple dose) cartridges , automatic index. RUBBER • Rubber closures are used for secondary seal that holds the primary seal in place. • Aluminum caps are used for parenterals packaging. vignan pharmacy college 47
  48. 48. QUALITY CONTROL OF PARENTERAL PREPARATIONS vignan pharmacy college 48
  49. 49. LEAKAGE TEST QUALITY CONTROL TEST CLARITY TEST STERILITY TEST PYROGEN TEST vignan pharmacy college 49
  50. 50. LEAKAGE TEST Take the ampoules or vials containing sample Invert the ampoules in 1% methylene blue solution Observe colour of the sample before and after test If colour change occur leakage present. If colour change does not occur leakage absent. vignan pharmacy college 50
  51. 51. MICROSCOPIC COUNT METHOD CLARITY TEST COULTER COUNTER METHOD LIGHT OBSTRUCTION METHOD VISUAL METHOD vignan pharmacy college 51
  52. 52. • The ampoules are placed in dark back - ground observe light particles. • Light back ground observe dark particles. VISUAL METHOD • A measure sample solution is filtered through membrane filters. • Particles observe in the microscope under 100x magnification. MICROSCOPIC COUNT METHOD • The particles observe in the solution cross the light beam by using light beam instrument. • The particles measured and counted. LIGHT OBSTRUCTIVE METHOD vignan pharmacy college 52
  53. 53. Visual inspection light beam vignan pharmacy college 53
  54. 54. Permissible limits for particulate matter according to I.P PARTICAL SIZE MAXIMUM NUMBER OF PARTICALS(ML) 10 50 25 5 50 Nill vignan pharmacy college 54
  55. 55. • 2 vignan pharmacy college 55
  56. 56. vignan pharmacy college 56
  57. 57. vignan pharmacy college 57  RESULT  The test is positive when each rabbit show increase in the temperature it only 2 of the three rabbits show increase in temperature.  The test using group of five and test will be positive if the four of the rabbits show increase the temperature.  DISADVANTAGES  Biological variation  Expensive  Laborious  Dose dependent  Not for antipyretic drugs
  58. 58. LAL BACTERIAL ENDOTOXIN TEST  The LAL (limulus amebolyte lysate) assay is an vitro assay used to detect the presence and concentration of bacterial endotoxins in drugs one biological product.  Endotoxins which are a type of pyrogen are lipopolysaccharides present in the cell walls of gram negative bacteria.  Pyrogens as a class are fever-inducing substances that can be harmful or even fatel if administered to humans above certain concentrations.  Water can be a source of pyrogen so it may be important to routinely monitor water systems using to bacterial endotoxins test. vignan pharmacy college 58
  59. 59. CRITERIA FOR LIMULUS TEST RESULT LAL TUBE TEST SAMPLE/CONTROL RESULT 1 Negative control (pyrogen free saline) Should be -ve 2 Positive control(pyrogen) Should be +ve 3 Positive internal control (test sample tainted with exdotoxines) Should be +ve 4 Test for sample May be +ve or -ve vignan pharmacy college 59
  60. 60. 1. Membrane Filtration vignan pharmacy college 60 Method
  61. 61.  Parenterals are the most reliable and promising formulation which avoid first pass metabolism and provide 100% bioavailability. vignan pharmacy college 61 6-9 2014
  62. 62. References 1. Sandeep Nema, John D.Ludwing pharmaceutical dosage forms volume-I (pg:1-358) and volume-II (pg:-1-56,221-353). 2. Jain Gupta modern dispensing pharmacy (pg:-357-375). 3. Loyd V.Allen, Jr Nicholas G.popovich Howandc.Ansel- ANSEL’S Pharmaceutical dosage forms and drug delivery system (pg:-443-540). vignan pharmacy college 62
  63. 63. References 4. Leon Lachman,Herbert A.lieberman The theory and practice of industrial pharmacy (pg:-619-6390). 5. Martin’s Physical pharmacy and pharmaceutical sciences (pg:-634-635). 6. Umang H.Shah,Ashok H.Arabari,Amitkumar baser GPAT and other competitive examination in pharmacy (pg:-1.65-1.70) vignan pharmacy college 63
  64. 64. ACKNOWLEDGEMENT  Thank you for paying attention.  I also sincerely thank my guide Mrs.K.PALLAVI madam for the valuable guidance and support.  I sincerely thank our principal Dr. P. Srinivasa babu sir for the constant encouragement.  A special thanks to seminar committee for giving me this opportunity. vignan pharmacy college 64
  65. 65. vignan pharmacy college 65

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