logging in or signing up PARENTERALS vicky_5593 Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 2729 Category: Science & Tech.. License: All Rights Reserved Like it (6) Dislike it (0) Added: April 10, 2011 This Presentation is Public Favorites: 4 Presentation Description No description available. Comments Posting comment... By: vicky_5593 (4 days ago) Pls give me your mail id , i will surely mail you this ppt. sorry for late reply. Saving..... Post Reply Close Saving..... Edit Comment Close By: sriiintegrity (9 month(s) ago) hi please send this presentation to me. my email: sriintegrity@gmail.com Saving..... Post Reply Close Saving..... 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See all Premium member Presentation Transcript Slide 1: PARENTERALS Submitted By- Vikramjit Singh Submitted To- Dr. Nawazish Alam S.B.S College Of Pharmacy Patti (T.T) 1 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011PARENTERAL: The term parenteral derived from the Greek words: para (outside) and enteron, (intestine) denotes routes of administration other than oral route. refers to the injectable routes administration. sterile PARENTERAL INJECTIONS pyrogen free preparations intended to be administered parenterally. 2 Vikramjit Singh,"Dr,Nawazish Alam" PARENTERAL 4/10/2011Based on the route of administration, sterile products are classified into:: 1. Parenteral preparations 2. Ophthalmic preparations - for the eye 3. Otic preparations - for the ear 4. Nasal preparations - for the nose & throat 5. Irrigating solutions - for washing wounds or abraded mucous membrane 3 Vikramjit Singh,"Dr,Nawazish Alam" Based on the route of administration, sterile products are classified into: 4/10/2011Routes of administration: Intra Muscular (IM) Intra dermal (ID) Intravenous (IV) Subcutaneous / Hypodermic (SC) Intra articular Intra synovial Intra spinal Intrathecal Intrarterial Intra cardiac Intra cisternal Intra peritonial Intraplueral 4 Vikramjit Singh,"Dr,Nawazish Alam" Routes of administration 4/10/2011Parenteral Routes of Administration: Vikramjit Singh,"Dr,Nawazish Alam" 5 Parenteral Routes of Administration 1. Intra-articular –joints 2. Intraspinal –spinal column 3. Intra-arterial –arteries 4. Intravenous –veins 5. Intradermal –shin 6. Intrasynovial –joint fluid 7. Intrathecal –spinal fluid 8. Intracardiac –heart 9. Intramuscular –muscles 10. Subcutaneous –under the skin 4/10/2011TYPES OF PARENTERALS : Powder for injection -Eg. Cefuroxime for injection Colloidal solution - Eg. Iron dextran Injectable emulsion-Eg. Propofol USP Injectable suspension –Eg. Methylprednisolone acetate Oily injection (solution)-Eg. Dimercaprol injection. Infusion fluid 6 Vikramjit Singh,"Dr,Nawazish Alam" TYPES OF PARENTERALS 4/10/2011Slide 7: Oral Benefit Injectable Less expensive Administrable to nonresponsive patients Patient convenience and comfort Administrable directly to site of action Retrievable, if necessary Better absorption Description Rapid onset of action 7 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011Slide 8: Bulk Procurement Form/Fill Finish Affiliate Distribution Wholesaler Retail Consumer Parenteral Manufacturing Supply Chain & Production Planning 8 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011PREFORMULATION FACTORS:: It is study about physical & chemical properties of drug substance prior formulation is called as preformulation. They are pH Solubilty pka Dissociation constant Compatabilty studies- FTIR / DSC Oxidation & reduction particle size 9 Vikramjit Singh,"Dr,Nawazish Alam" PREFORMULATION FACTORS : 4/10/2011FORMULATION OF PARENTERALS: 1. Solutes 2.Added substance Antimicrobial agent Buffers Antioxidants Tonicity agent Cryoprotectant Suspending agent Emulsifying agent 3.Vehicle Aqueous -WFI Non- aqueous Eg. arachis oil 10 Vikramjit Singh,"Dr,Nawazish Alam" FORMULATION OF PARENTERALS 4/10/2011Such substances include:: 1. Solubilizers 2. Chelating agents 3. Anti-microbial agents 4. Hydrolysis Inhibitors 5. Antioxidants 6. Buffers 7. Tonicity contributors 8. Antifoaming agents 11 Vikramjit Singh,"Dr,Nawazish Alam" Such substances include: 4/10/2011GENERAL PROCEDURE: Cleaning & washing of container ,closures Preparation of solutions Sterilizaation (Filteration) Filling Packaging 12 Vikramjit Singh,"Dr,Nawazish Alam" GENERAL PROCEDURE 4/10/2011Lyophilization techniques: It is a process of removal of solvent from the product or substances is called as lyophilization. It consist of three steps Freezing Primary drying Secondary drying 13 Vikramjit Singh,"Dr,Nawazish Alam" Lyophilization techniques 4/10/2011Creteria for parenterals: Sterility Pyrogen Isotonicity Stability Ph Osmotic pressure 14 Vikramjit Singh,"Dr,Nawazish Alam" Creteria for parenterals 4/10/2011Containers & closures: 1.Glass 2.Plastic Ampoules( single dose ) Vials( multiple dose) Cartridges Automatic injector 3.Rubber closure with aluminium caps Small volume parenterals: less than 100ml Large volume parenterals : more than 100ml 15 Vikramjit Singh,"Dr,Nawazish Alam" Containers & closures 4/10/2011Formulation of SVP: Aqueous vehicle : Water For Injection(WFI) USP : Highly purified water used as a vehicle for injectable preparations which will be subsequently sterilized. USP requirement include not more than 10 parts per million of total solids. pH of 5.0 to 7.0 WFI may prepared by either distillation or reverse osmosis. Stored for less than 24hr at RT or for longer times at specific temperatures. Should be meet USP pyrogen test It may not contain any added substances. Stored in chemically resistant tank. 16 Vikramjit Singh,"Dr,Nawazish Alam" Formulation of SVP 4/10/2011Slide 17: Bacteriostatic Water for Injection (BWFI) : 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 30ml or less 17 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011Slide 18: Sterile Water for Injection USP SWFI containing one or more suitable bacteriostatic agents. Multiple-dose containers not exceeding 30 ml. They are permitted to contain higher levels of than WFI because of the possible leaching of glass container. Sterile Water for Irrigation. Wash wounds, surgical incisions, or body tissues. 18 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011MANUFACTURING OF SVP: Vikramjit Singh,"Dr,Nawazish Alam" 19 MANUFACTURING OF SVP 4/10/2011Slide 20: Vikramjit Singh,"Dr,Nawazish Alam" 20 4/10/2011Official Types of Injections: 1. Drug Injection - Liquid preparations that are drug substances or solutions thereof. Example: Insulin Injection, USP 2. Drug for Injection - Dry solids that, upon the addition of suitable vehicles, yield solutions conforming in all respects to the requirement for Injections Example: Cefamandole Sodium for Injection 21 Vikramjit Singh,"Dr,Nawazish Alam" Official Types of Injections 4/10/2011Slide 22: 3. Drug Injectable Emulsion - Liquid preparations of drug substances dissolved or dispersed in a suitable emulsion medium Example: Propofol Official Types of Injections Vikramjit Singh,"Dr,Nawazish Alam" 22 4/10/2011Slide 23: 4. Drug Injectable Suspension - Liquid preparations of solids suspended in a suitable liquid medium Example: Methylprednisolone Acetate Suspension 5. Drug Injectable Suspension - Dry solids that, upon the preparations conforming in all respects to the requirements for Injectable Suspensions Example: Imipenem; Cilastatin for Injection Suspension, USP 23 Vikramjit Singh,"Dr,Nawazish Alam" Official Types of Injections 4/10/2011Characteristics Of Components used in Compounding: 1. Therapeutically effective when used as the active ingredients 2. Provide maximum safety 3. Function efficiently (when used as excipient) 4. Free from contamination 5. Physically and chemically stable even after thermal sterilization 6. Produce little or no tissue irritation at site of administration 24 Vikramjit Singh,"Dr,Nawazish Alam" Characteristics Of Components used in Compounding 4/10/2011Nonaqueous Vehicles Selected Vehicles must be:: 1. Nonirritating 2. Non toxic in the amounts administered 3. Nonsensitizing 4. It must not exert a pharmacologic activity 5. May not adversely affect the activity of the medicinal agent 25 Vikramjit Singh,"Dr,Nawazish Alam" Nonaqueous Vehicles Selected Vehicles must be: 4/10/2011Other Considerations Of Selecting Nonaqueous Solvents: 1. Physical and chemical stability 2. Its viscosity (syringeability) and its fluidity 3. Its boiling point (it should be high to permit heat sterilization) 4. Its miscibility with body fluids 5. Its low vapor pressure to avoid problems during heat sterilization 6. Constant purity or ease of purification and standardization. 26 Vikramjit Singh,"Dr,Nawazish Alam" Other Considerations Of Selecting Nonaqueous Solvents 4/10/2011Examples of Nonaqueous Solvents: 1. Fixed vegetable oils 2. Glycerin 3. Polyethylene glycols 4. Propylene glycol 5. Ethyl oleate 6. Isopropyl myristate 7. Methylacetamide 8. Alcohol 27 Vikramjit Singh,"Dr,Nawazish Alam" Examples of Nonaqueous Solvents 4/10/2011Nonaqueous Vehicles…: Examples of Fixed Oils Commonly Used in Injections 1. Corn Oil 2. Cottonseed seed Oil 3. Peanut Oil 4. Sesame Oil 5. Castor Oil and Olive Oil (occasion) 28 Vikramjit Singh,"Dr,Nawazish Alam" Nonaqueous Vehicles… 4/10/2011Slide 29: Compounding Processing of sterile preparations follow normal manufacturing procedures which must be done in aseptic condition. All equipment and materials used whenever possible must be sterile 29 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011Slide 30: Filtration Membrane filters are used for clarification when a highly polished solution is desired. The process removes particulates matter down to at least 3 microns in size. Sterilization by filtration is achieved when viable microorganisms and spores of approximately 0.3 microns are removed. Membranes with porosity ratings of 0.22 or 0.45 microns are usually specified for sterile filtration. Vikramjit Singh,"Dr,Nawazish Alam" 30 4/10/2011Slide 31: Filling Bulk preparations are subdivided into unit dose containers during filling. This process forces a measured volume of the preparation through the orifices of a delivery tube designed to enter the constricted opening of a container by means of gravity, vacuum or with the aid of a pressure pump. Sealing Sealing will retain the contents of a sterile product and will assure a tamper-proof presentation. Vikramjit Singh,"Dr,Nawazish Alam" 31 4/10/2011Large Volume Parenterals (LVPs): These solutions are usually administered by IV infusion to replenish body fluids, electrolytes, or to provide nutrition. They are usually administered in volumes of 100 mL to liter amounts and more per day by slow intravenous infusion with or without controlled-rate infusion systems 32 Vikramjit Singh,"Dr,Nawazish Alam" Large Volume Parenterals (LVPs) 4/10/2011Slide 33: USES: 1. Employed as Maintenance therapy for the patient entering or recovering from surgery, or for the patient who is unconscious and unable to obtain fluids, electrolytes, and nutrition orally. 2. Utilized as Replacement therapy in patients who have suffered a heavy loss of fluid and electrolytes. Vikramjit Singh,"Dr,Nawazish Alam" 33 4/10/2011Slide 34: Irrigation and Dialysis Solutions Solutions for irrigation of body tissues and dor dialysis resemble parenteral solutions in that they are subject to the same stringent standards. These solutions are not injected into the vein, but employed outside of the circulatory system. Vikramjit Singh,"Dr,Nawazish Alam" 34 4/10/2011Slide 35: Irrigation Solutions Irrigation solutions are intended to bathe or wash wounds, surgical incisions, or body tissues. Dialysis Solutions May be defined as a process whereby substances may be separated from one another in solution by taking advantage of their differing diffusibility through membranes 35 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011Area of parenterals processing : Vikramjit Singh,"Dr,Nawazish Alam" 36 Area of parenterals processing 4/10/2011Slide 37: Vikramjit Singh,"Dr,Nawazish Alam" 37 Preparation Area: The materials utilized for the production of the sterile products move toward the preparation area through a series of progressively cleaner environments. First the materials are passed through class 100,000 i.e. grade D environment for presterilization. Transfer of materials are carried out in air-locks to avoid cross contamination 4/10/2011Slide 38: Vikramjit Singh,"Dr,Nawazish Alam" 38 The preparation areas are supplied with HEPA filters. There should be more than 20 air changes per hour The preparation place is Class 100 area. 4/10/2011Production area: Vikramjit Singh,"Dr,Nawazish Alam" 39 Production area 4/10/2011Slide 40: Vikramjit Singh,"Dr,Nawazish Alam" 40 Compounding area: The manufacture of parenterals is carried out in class 10,000 (Grade C) controlled environments in which class 100 unidirectional flow hoods are utilized to provide greater environmental control during material addition. These areas are designed to minimize the microbial, pyrogen , and particulate contamination to the formulation prior to sterilization. 4/10/2011Instrumentation : Vikramjit Singh,"Dr,Nawazish Alam" 41 Instrumentation Mixer Homogenizer Filteration assembly Filling machinery 4/10/2011Mixer/Homogenizer: Vikramjit Singh,"Dr,Nawazish Alam" 42 Mixer/Homogenizer 4/10/2011Filtration assembly: Vikramjit Singh,"Dr,Nawazish Alam" 43 Filtration assembly 4/10/2011Bottling/Filling machinery: Vikramjit Singh,"Dr,Nawazish Alam" 44 Bottling/Filling machinery 4/10/2011Slide 45: Filling Line – Traditional Method – Vials Filling Vikramjit Singh,"Dr,Nawazish Alam"Sterilization and Depyrogenation: Vikramjit Singh,"Dr,Nawazish Alam" 46 Sterilization and Depyrogenation Steam sterilization Dry-heat sterilization and depyrogenation Gas and vapour sterilization Radiation sterilization Sterilization by filteration 4/10/2011Particulate matter detector: Vikramjit Singh,"Dr,Nawazish Alam" 47 Particulate matter detector 4/10/2011Filtration assembly : Vikramjit Singh,"Dr,Nawazish Alam" 48 Filtration assembly 4/10/2011General flow chart : Vikramjit Singh,"Dr,Nawazish Alam" 49 General flow chart Raw Materials Measured and weighed Mixing Filling Packing Distilled water Finished products storage Quality Assurance 4/10/2011Evaluation test for parenterals: Test for pyrogen Sterilty testing Rabbit test Clarity test LAL test Leaker test 50 Vikramjit Singh,"Dr,Nawazish Alam" Evaluation test for parenterals 4/10/2011Slide 51: Air Quality Facilities are divided into 4 grades of air quality: Grade A – Exposed Product Grade B – Adjacent to Product (Operators fully gowned) Grade C – Non- Sterile Production area (Formulation) Grade D – General Corridors A (Exposed Product) B C D Facility 51 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011Slide 52: Garments Keep the operator from spreading any unwanted contaminants to the product and environment. People Practices Vikramjit Singh,"Dr,Nawazish Alam"Slide 53: Sterile Filtration Non-Sterile Sterile Vikramjit Singh,"Dr,Nawazish Alam"QUALITY ASSURANCE: It includes : - Material management - Equipment and facility management - Personnel management - Documentation control 54 Vikramjit Singh,"Dr,Nawazish Alam" QUALITY ASSURANCE 4/10/2011Slide 55: Pyrogen test : Pyrogenic - means producing fever Pyrogens - fever inducing substances Endotoxins Produced mostly by gram-negative bacteria Endotoxin - complex of pyrogenic lipopolysaccharide, a protein and inert lipid. 55 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011Slide 56: LAL test : Limulus polyphemus = horseshoe crab Limulus - genera of crab Amebocyte - crab blood cell from which active component is derived Lysate - component is obtained by separating amebocytes from the plasma and then lysing them. The hearts of mature crabs are punctured and bled to collect the circulating amebocyte blood cells. 56 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011Slide 57: LEAKER TEST : Immersing the ampoules in a dye solution 1% metylene blue 25 in (64cm) of vacuum for a minimum of 15 min. The vacuum on the tank is then released as rapidly as possible to put maximum stress on weak seals. Defective ampoules will contain blue solution. 57 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011conclusion: A wide variety of devices and new methods of drug delivery employed. Each has its advantage and disadvantages, which have to be carefully considered by the therapist. One must understand and appreciate that since parenteral medications and frequently, body fluids or come into contact with most parenteral drug delivery devices. They must be free of contaminating microorganism, harmful substances, free of pyrogenic contamination, free of particulate matter. In coming future we can expect much more advance technology in utilizing parenteral products for safety desirable effects in human being. 58 Vikramjit Singh,"Dr,Nawazish Alam" conclusion 4/10/2011Slide 59: REFERENCES : Pharmaceutical Dosage Forms. Lieberman, Herbert A. Vol. 1: Parenteral Medications. Pharmaceutical Dosage Forms. Avis, Kenneth E. Vol. 2: Parenteral Medications Pharmaceutical Dosage Forms. Avis, Kenneth E Vol. 3 : Parenteral Medications Parenteral Quality Control. Michael J. Akers and Daniel S. Larrimore (Marcel Dekker, second edition.1993). Modern Pharmaceutics. Gilbert S. Banker, Christopher T. Rhodes. Fourth Edition. www.google.com www.pharmaceuticalonline.com The Theory & Practice Of Industrial Pharmacy Lieberman , Lachman Special Indian Edition. 59 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011 You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.
PARENTERALS vicky_5593 Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 2729 Category: Science & Tech.. License: All Rights Reserved Like it (6) Dislike it (0) Added: April 10, 2011 This Presentation is Public Favorites: 4 Presentation Description No description available. Comments Posting comment... By: vicky_5593 (4 days ago) Pls give me your mail id , i will surely mail you this ppt. sorry for late reply. Saving..... Post Reply Close Saving..... Edit Comment Close By: sriiintegrity (9 month(s) ago) hi please send this presentation to me. my email: sriintegrity@gmail.com Saving..... Post Reply Close Saving..... Edit Comment Close By: maxpyane (10 month(s) ago) can you please allow me to download this... that will be helpful to my students .. I promise you i will follow copyright by you.. thanks Saving..... Post Reply Close Saving..... Edit Comment Close By: rajkumarg (10 month(s) ago) hi dude plz mail me this ppt. my email id is rajkumar.gutmal@gmail.com Saving..... Post Reply Close Saving..... Edit Comment Close By: SunnyXav (12 month(s) ago) sir it is nice ppt . plz send me on my id shrutigangwar10@gmail.com Saving..... Post Reply Close Saving..... Edit Comment Close loading.... See all Premium member Presentation Transcript Slide 1: PARENTERALS Submitted By- Vikramjit Singh Submitted To- Dr. Nawazish Alam S.B.S College Of Pharmacy Patti (T.T) 1 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011PARENTERAL: The term parenteral derived from the Greek words: para (outside) and enteron, (intestine) denotes routes of administration other than oral route. refers to the injectable routes administration. sterile PARENTERAL INJECTIONS pyrogen free preparations intended to be administered parenterally. 2 Vikramjit Singh,"Dr,Nawazish Alam" PARENTERAL 4/10/2011Based on the route of administration, sterile products are classified into:: 1. Parenteral preparations 2. Ophthalmic preparations - for the eye 3. Otic preparations - for the ear 4. Nasal preparations - for the nose & throat 5. Irrigating solutions - for washing wounds or abraded mucous membrane 3 Vikramjit Singh,"Dr,Nawazish Alam" Based on the route of administration, sterile products are classified into: 4/10/2011Routes of administration: Intra Muscular (IM) Intra dermal (ID) Intravenous (IV) Subcutaneous / Hypodermic (SC) Intra articular Intra synovial Intra spinal Intrathecal Intrarterial Intra cardiac Intra cisternal Intra peritonial Intraplueral 4 Vikramjit Singh,"Dr,Nawazish Alam" Routes of administration 4/10/2011Parenteral Routes of Administration: Vikramjit Singh,"Dr,Nawazish Alam" 5 Parenteral Routes of Administration 1. Intra-articular –joints 2. Intraspinal –spinal column 3. Intra-arterial –arteries 4. Intravenous –veins 5. Intradermal –shin 6. Intrasynovial –joint fluid 7. Intrathecal –spinal fluid 8. Intracardiac –heart 9. Intramuscular –muscles 10. Subcutaneous –under the skin 4/10/2011TYPES OF PARENTERALS : Powder for injection -Eg. Cefuroxime for injection Colloidal solution - Eg. Iron dextran Injectable emulsion-Eg. Propofol USP Injectable suspension –Eg. Methylprednisolone acetate Oily injection (solution)-Eg. Dimercaprol injection. Infusion fluid 6 Vikramjit Singh,"Dr,Nawazish Alam" TYPES OF PARENTERALS 4/10/2011Slide 7: Oral Benefit Injectable Less expensive Administrable to nonresponsive patients Patient convenience and comfort Administrable directly to site of action Retrievable, if necessary Better absorption Description Rapid onset of action 7 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011Slide 8: Bulk Procurement Form/Fill Finish Affiliate Distribution Wholesaler Retail Consumer Parenteral Manufacturing Supply Chain & Production Planning 8 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011PREFORMULATION FACTORS:: It is study about physical & chemical properties of drug substance prior formulation is called as preformulation. They are pH Solubilty pka Dissociation constant Compatabilty studies- FTIR / DSC Oxidation & reduction particle size 9 Vikramjit Singh,"Dr,Nawazish Alam" PREFORMULATION FACTORS : 4/10/2011FORMULATION OF PARENTERALS: 1. Solutes 2.Added substance Antimicrobial agent Buffers Antioxidants Tonicity agent Cryoprotectant Suspending agent Emulsifying agent 3.Vehicle Aqueous -WFI Non- aqueous Eg. arachis oil 10 Vikramjit Singh,"Dr,Nawazish Alam" FORMULATION OF PARENTERALS 4/10/2011Such substances include:: 1. Solubilizers 2. Chelating agents 3. Anti-microbial agents 4. Hydrolysis Inhibitors 5. Antioxidants 6. Buffers 7. Tonicity contributors 8. Antifoaming agents 11 Vikramjit Singh,"Dr,Nawazish Alam" Such substances include: 4/10/2011GENERAL PROCEDURE: Cleaning & washing of container ,closures Preparation of solutions Sterilizaation (Filteration) Filling Packaging 12 Vikramjit Singh,"Dr,Nawazish Alam" GENERAL PROCEDURE 4/10/2011Lyophilization techniques: It is a process of removal of solvent from the product or substances is called as lyophilization. It consist of three steps Freezing Primary drying Secondary drying 13 Vikramjit Singh,"Dr,Nawazish Alam" Lyophilization techniques 4/10/2011Creteria for parenterals: Sterility Pyrogen Isotonicity Stability Ph Osmotic pressure 14 Vikramjit Singh,"Dr,Nawazish Alam" Creteria for parenterals 4/10/2011Containers & closures: 1.Glass 2.Plastic Ampoules( single dose ) Vials( multiple dose) Cartridges Automatic injector 3.Rubber closure with aluminium caps Small volume parenterals: less than 100ml Large volume parenterals : more than 100ml 15 Vikramjit Singh,"Dr,Nawazish Alam" Containers & closures 4/10/2011Formulation of SVP: Aqueous vehicle : Water For Injection(WFI) USP : Highly purified water used as a vehicle for injectable preparations which will be subsequently sterilized. USP requirement include not more than 10 parts per million of total solids. pH of 5.0 to 7.0 WFI may prepared by either distillation or reverse osmosis. Stored for less than 24hr at RT or for longer times at specific temperatures. Should be meet USP pyrogen test It may not contain any added substances. Stored in chemically resistant tank. 16 Vikramjit Singh,"Dr,Nawazish Alam" Formulation of SVP 4/10/2011Slide 17: Bacteriostatic Water for Injection (BWFI) : 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 30ml or less 17 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011Slide 18: Sterile Water for Injection USP SWFI containing one or more suitable bacteriostatic agents. Multiple-dose containers not exceeding 30 ml. They are permitted to contain higher levels of than WFI because of the possible leaching of glass container. Sterile Water for Irrigation. Wash wounds, surgical incisions, or body tissues. 18 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011MANUFACTURING OF SVP: Vikramjit Singh,"Dr,Nawazish Alam" 19 MANUFACTURING OF SVP 4/10/2011Slide 20: Vikramjit Singh,"Dr,Nawazish Alam" 20 4/10/2011Official Types of Injections: 1. Drug Injection - Liquid preparations that are drug substances or solutions thereof. Example: Insulin Injection, USP 2. Drug for Injection - Dry solids that, upon the addition of suitable vehicles, yield solutions conforming in all respects to the requirement for Injections Example: Cefamandole Sodium for Injection 21 Vikramjit Singh,"Dr,Nawazish Alam" Official Types of Injections 4/10/2011Slide 22: 3. Drug Injectable Emulsion - Liquid preparations of drug substances dissolved or dispersed in a suitable emulsion medium Example: Propofol Official Types of Injections Vikramjit Singh,"Dr,Nawazish Alam" 22 4/10/2011Slide 23: 4. Drug Injectable Suspension - Liquid preparations of solids suspended in a suitable liquid medium Example: Methylprednisolone Acetate Suspension 5. Drug Injectable Suspension - Dry solids that, upon the preparations conforming in all respects to the requirements for Injectable Suspensions Example: Imipenem; Cilastatin for Injection Suspension, USP 23 Vikramjit Singh,"Dr,Nawazish Alam" Official Types of Injections 4/10/2011Characteristics Of Components used in Compounding: 1. Therapeutically effective when used as the active ingredients 2. Provide maximum safety 3. Function efficiently (when used as excipient) 4. Free from contamination 5. Physically and chemically stable even after thermal sterilization 6. Produce little or no tissue irritation at site of administration 24 Vikramjit Singh,"Dr,Nawazish Alam" Characteristics Of Components used in Compounding 4/10/2011Nonaqueous Vehicles Selected Vehicles must be:: 1. Nonirritating 2. Non toxic in the amounts administered 3. Nonsensitizing 4. It must not exert a pharmacologic activity 5. May not adversely affect the activity of the medicinal agent 25 Vikramjit Singh,"Dr,Nawazish Alam" Nonaqueous Vehicles Selected Vehicles must be: 4/10/2011Other Considerations Of Selecting Nonaqueous Solvents: 1. Physical and chemical stability 2. Its viscosity (syringeability) and its fluidity 3. Its boiling point (it should be high to permit heat sterilization) 4. Its miscibility with body fluids 5. Its low vapor pressure to avoid problems during heat sterilization 6. Constant purity or ease of purification and standardization. 26 Vikramjit Singh,"Dr,Nawazish Alam" Other Considerations Of Selecting Nonaqueous Solvents 4/10/2011Examples of Nonaqueous Solvents: 1. Fixed vegetable oils 2. Glycerin 3. Polyethylene glycols 4. Propylene glycol 5. Ethyl oleate 6. Isopropyl myristate 7. Methylacetamide 8. Alcohol 27 Vikramjit Singh,"Dr,Nawazish Alam" Examples of Nonaqueous Solvents 4/10/2011Nonaqueous Vehicles…: Examples of Fixed Oils Commonly Used in Injections 1. Corn Oil 2. Cottonseed seed Oil 3. Peanut Oil 4. Sesame Oil 5. Castor Oil and Olive Oil (occasion) 28 Vikramjit Singh,"Dr,Nawazish Alam" Nonaqueous Vehicles… 4/10/2011Slide 29: Compounding Processing of sterile preparations follow normal manufacturing procedures which must be done in aseptic condition. All equipment and materials used whenever possible must be sterile 29 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011Slide 30: Filtration Membrane filters are used for clarification when a highly polished solution is desired. The process removes particulates matter down to at least 3 microns in size. Sterilization by filtration is achieved when viable microorganisms and spores of approximately 0.3 microns are removed. Membranes with porosity ratings of 0.22 or 0.45 microns are usually specified for sterile filtration. Vikramjit Singh,"Dr,Nawazish Alam" 30 4/10/2011Slide 31: Filling Bulk preparations are subdivided into unit dose containers during filling. This process forces a measured volume of the preparation through the orifices of a delivery tube designed to enter the constricted opening of a container by means of gravity, vacuum or with the aid of a pressure pump. Sealing Sealing will retain the contents of a sterile product and will assure a tamper-proof presentation. Vikramjit Singh,"Dr,Nawazish Alam" 31 4/10/2011Large Volume Parenterals (LVPs): These solutions are usually administered by IV infusion to replenish body fluids, electrolytes, or to provide nutrition. They are usually administered in volumes of 100 mL to liter amounts and more per day by slow intravenous infusion with or without controlled-rate infusion systems 32 Vikramjit Singh,"Dr,Nawazish Alam" Large Volume Parenterals (LVPs) 4/10/2011Slide 33: USES: 1. Employed as Maintenance therapy for the patient entering or recovering from surgery, or for the patient who is unconscious and unable to obtain fluids, electrolytes, and nutrition orally. 2. Utilized as Replacement therapy in patients who have suffered a heavy loss of fluid and electrolytes. Vikramjit Singh,"Dr,Nawazish Alam" 33 4/10/2011Slide 34: Irrigation and Dialysis Solutions Solutions for irrigation of body tissues and dor dialysis resemble parenteral solutions in that they are subject to the same stringent standards. These solutions are not injected into the vein, but employed outside of the circulatory system. Vikramjit Singh,"Dr,Nawazish Alam" 34 4/10/2011Slide 35: Irrigation Solutions Irrigation solutions are intended to bathe or wash wounds, surgical incisions, or body tissues. Dialysis Solutions May be defined as a process whereby substances may be separated from one another in solution by taking advantage of their differing diffusibility through membranes 35 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011Area of parenterals processing : Vikramjit Singh,"Dr,Nawazish Alam" 36 Area of parenterals processing 4/10/2011Slide 37: Vikramjit Singh,"Dr,Nawazish Alam" 37 Preparation Area: The materials utilized for the production of the sterile products move toward the preparation area through a series of progressively cleaner environments. First the materials are passed through class 100,000 i.e. grade D environment for presterilization. Transfer of materials are carried out in air-locks to avoid cross contamination 4/10/2011Slide 38: Vikramjit Singh,"Dr,Nawazish Alam" 38 The preparation areas are supplied with HEPA filters. There should be more than 20 air changes per hour The preparation place is Class 100 area. 4/10/2011Production area: Vikramjit Singh,"Dr,Nawazish Alam" 39 Production area 4/10/2011Slide 40: Vikramjit Singh,"Dr,Nawazish Alam" 40 Compounding area: The manufacture of parenterals is carried out in class 10,000 (Grade C) controlled environments in which class 100 unidirectional flow hoods are utilized to provide greater environmental control during material addition. These areas are designed to minimize the microbial, pyrogen , and particulate contamination to the formulation prior to sterilization. 4/10/2011Instrumentation : Vikramjit Singh,"Dr,Nawazish Alam" 41 Instrumentation Mixer Homogenizer Filteration assembly Filling machinery 4/10/2011Mixer/Homogenizer: Vikramjit Singh,"Dr,Nawazish Alam" 42 Mixer/Homogenizer 4/10/2011Filtration assembly: Vikramjit Singh,"Dr,Nawazish Alam" 43 Filtration assembly 4/10/2011Bottling/Filling machinery: Vikramjit Singh,"Dr,Nawazish Alam" 44 Bottling/Filling machinery 4/10/2011Slide 45: Filling Line – Traditional Method – Vials Filling Vikramjit Singh,"Dr,Nawazish Alam"Sterilization and Depyrogenation: Vikramjit Singh,"Dr,Nawazish Alam" 46 Sterilization and Depyrogenation Steam sterilization Dry-heat sterilization and depyrogenation Gas and vapour sterilization Radiation sterilization Sterilization by filteration 4/10/2011Particulate matter detector: Vikramjit Singh,"Dr,Nawazish Alam" 47 Particulate matter detector 4/10/2011Filtration assembly : Vikramjit Singh,"Dr,Nawazish Alam" 48 Filtration assembly 4/10/2011General flow chart : Vikramjit Singh,"Dr,Nawazish Alam" 49 General flow chart Raw Materials Measured and weighed Mixing Filling Packing Distilled water Finished products storage Quality Assurance 4/10/2011Evaluation test for parenterals: Test for pyrogen Sterilty testing Rabbit test Clarity test LAL test Leaker test 50 Vikramjit Singh,"Dr,Nawazish Alam" Evaluation test for parenterals 4/10/2011Slide 51: Air Quality Facilities are divided into 4 grades of air quality: Grade A – Exposed Product Grade B – Adjacent to Product (Operators fully gowned) Grade C – Non- Sterile Production area (Formulation) Grade D – General Corridors A (Exposed Product) B C D Facility 51 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011Slide 52: Garments Keep the operator from spreading any unwanted contaminants to the product and environment. People Practices Vikramjit Singh,"Dr,Nawazish Alam"Slide 53: Sterile Filtration Non-Sterile Sterile Vikramjit Singh,"Dr,Nawazish Alam"QUALITY ASSURANCE: It includes : - Material management - Equipment and facility management - Personnel management - Documentation control 54 Vikramjit Singh,"Dr,Nawazish Alam" QUALITY ASSURANCE 4/10/2011Slide 55: Pyrogen test : Pyrogenic - means producing fever Pyrogens - fever inducing substances Endotoxins Produced mostly by gram-negative bacteria Endotoxin - complex of pyrogenic lipopolysaccharide, a protein and inert lipid. 55 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011Slide 56: LAL test : Limulus polyphemus = horseshoe crab Limulus - genera of crab Amebocyte - crab blood cell from which active component is derived Lysate - component is obtained by separating amebocytes from the plasma and then lysing them. The hearts of mature crabs are punctured and bled to collect the circulating amebocyte blood cells. 56 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011Slide 57: LEAKER TEST : Immersing the ampoules in a dye solution 1% metylene blue 25 in (64cm) of vacuum for a minimum of 15 min. The vacuum on the tank is then released as rapidly as possible to put maximum stress on weak seals. Defective ampoules will contain blue solution. 57 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011conclusion: A wide variety of devices and new methods of drug delivery employed. Each has its advantage and disadvantages, which have to be carefully considered by the therapist. One must understand and appreciate that since parenteral medications and frequently, body fluids or come into contact with most parenteral drug delivery devices. They must be free of contaminating microorganism, harmful substances, free of pyrogenic contamination, free of particulate matter. In coming future we can expect much more advance technology in utilizing parenteral products for safety desirable effects in human being. 58 Vikramjit Singh,"Dr,Nawazish Alam" conclusion 4/10/2011Slide 59: REFERENCES : Pharmaceutical Dosage Forms. Lieberman, Herbert A. Vol. 1: Parenteral Medications. Pharmaceutical Dosage Forms. Avis, Kenneth E. Vol. 2: Parenteral Medications Pharmaceutical Dosage Forms. Avis, Kenneth E Vol. 3 : Parenteral Medications Parenteral Quality Control. Michael J. Akers and Daniel S. Larrimore (Marcel Dekker, second edition.1993). Modern Pharmaceutics. Gilbert S. Banker, Christopher T. Rhodes. Fourth Edition. www.google.com www.pharmaceuticalonline.com The Theory & Practice Of Industrial Pharmacy Lieberman , Lachman Special Indian Edition. 59 Vikramjit Singh,"Dr,Nawazish Alam" 4/10/2011