Week 11 - Parenteral PDF

Types of Sterile Products  Parenterals  Ophthalmics  Topicals: burns and exposed skin  Systems and administration devices:  Dispersed systems:  Lipid microspheres, liposomes, microparticulates  Implants: Bone growth, fertility controls, sustained delivery...

Types of Sterile Products  Parenterals  Ophthalmics  Topicals: burns and exposed skin  Systems and administration devices:  Dispersed systems:  Lipid microspheres, liposomes, microparticulates  Implants: Bone growth, fertility controls, sustained delivery 1 Section VII Sterile dosage forms and delivery systems 15. Parenterals 2 In this section you will learn….  Parenteral routes of administration  Advantages and disadvantages  Solvents and vehicles for injections  Characteristics of parenterals  Industrial preparation  Packaging and labeling  Parenteral incompatibility 3 Parenterals Dosage form used outside of gastrointestinal tract (Not oral/nose route) A  Parenterel: Para = outside and enteron: intestine (outside alimentary tract)  Parenterals as sterile dosage forms:  Small- and large-volume injectable preparations - -  Irrigation fluids  Dialysis solutions  Injections: sterile, pyrogen free preparations administered parenterally  *Sterility here is very important: preparations come in direct - contact with the internal body fluids or tissues  infection can easily arise need to Sterilize !! : 4  Bloodstream/vens/muscles ↑ Advantages of Parenteral Administration Prolonged/Rapid action depends on type of injection (emulsion/suspension) & Were j  Viable in emergency: uncooperative, unconscious patient - - -  Provides: throua a casso injected into body -  Accurate dosage -  Localized effect: e.g.: dentistry goes to site of action & react > - - - Quickest and fastest action (cardiac arrest, asthma)  Prolonged action: e.g.: intra-articular steroids I  Alternative to other routes of delivery (e.g.: oral route)  Avoidance of:  GI enzymatic degradation and instability Problems 3 Oral route taa  Low and variable absorption the - suspensionInto muscle ↳ takes time for API to dissolve & muscle acts as bar for dug transfer 5 Disadvantages Advantages of Parenteral Administration -  Painful: Injections = pain!  Administration: Aseptically by trained personnel -  Rapid action: Difficult to reverse drug’s effects (inceled into body) -  Needle problems  Cost of manufacturing Chigh)  Packaging requirements ↳ to maketain stelity of product 6 Parenteral Routes of Administration  Drugs can be injected almost in any part of the body  Most Common: -understein  Subcutaneous (SC) Small amount (-1 3ml) ~.  Intravenous (IV) veins -  Intramuscular (IM) muscles -  Intradermal (ID, into the skin) -  Others:  Intraarticular (joint)  Intrathecal (spinal fluid)  Intracardiac (heart)  Intraspinal (spinal column)  Intra-arterial (arteries)  Intrasynovial (joint fluid 7 area) Parenteral Routes of Administration directly into blood stream  - Intravenous route: Veins  Rapid action, accurate, lifesaving in emergency -  Intramuscular route: Muscles  Drug action is less rapid but of greater duration creus] - compared to intravenous route  Injected in skeletal muscles away from major nerves and vessels requires trained personne  Subcutaneous route:  Injection beneath the surface of the skin in small - amounts 1.3 mL - 8 Official Types of Injection directly injected into site of action -  Injection: liquid preparations that are drug solutions or - - substances (Insulin Injection)  For injection: dry solids or liquid concentrate - need - - addition of solvent (Cefuroxime) & shake well > once dissolved inject - - ,  Injectable emulsion: drug dissolved or dispersed in an emulsion medium (Propofol) directlyInfect into body  Injectable suspension: preparation of solids in a liquid medium (Methylprednisolone acetate suspension)  For injectable suspension: dry solids, which upon the addition of suitable vehicles yield preparations conforming in all respects to the requirements for injectable suspensions (Imipenem and cilastatin) 9 Unique Characteristics of Parenterals  Sterile Liposaccharides from Bacteria cell wall -  Pyrogen free -  Particulate free: for large-volume parenterals: A Not more than 50 particles/ml that are equal to or larger than 10 µm and not more than 5 particles/ml that are equal to or larger than 25 µm  Not more than 10,000 particles/container that are equal to or larger than 10 µm and not more than 1000 particles/container that are equal to or larger than 25 µm 10 Requirements for Solutions and Suspensions to be Used for Injections  Solvents / vehicles: must meet purity and safety standards To Irritations -  Must be sterile and pyrogen - free  Must be prepared under aseptic conditions (minimised)  Restrictions on buffers, stabilizers, antimicrobial preservative. Coloring - X agents strictly prohibited A  Must meet standards for particulate matter (Ime or/container -  Packaged in hermetic containers of specific and high quality. Filled in slight excess for easy withdrawal  Sterilized powders intended for solutions or suspensions are packed as lyophilized or freeze-dried powders  Specific labeling regulations apply 11 Lyophilization (Freeze-drying) - lot powders  Process of drying in which water is sublimed from the - - product after it is frozen  steps: ① Freezing an aqueous product (Freeze-drying) ② Evacuate the chamber (usually below 0.1 torr = 100 micrometers Hg) using vacuum ③ Introducing heat to the product to allow for subliming of ice into a- - - cold condensing surface 12 Parenteral Ingredients/Necessities ↳ S  Vehicle Depends dosage forms used on -  Buffers  Antioxidants  Antibacterial agents  Tonicity materials: dextrose, glycerin, mannitol, NaCl  Surfactants: egg and soybean phospholipids and lecithin  Thickeners  Preservatives: Multidose containers  Solubilizers, protectants, wetting agents, emulsifiers, local anesthetics, etc  Do not use color * > - 13  Vehicles for Injection  Solvent criteria: Non-irritating, non-toxic, non-sensitizing, - no pharmacological activity of its own and dose not - affect activity of medicinal agents  Must be sterile, particle and pyrogen free  Aqueous vehicles: - Water most frequently used and preferred  Types of water for Injections:  Water for Injection USP / Purified Water USP  Sterile Water for Injection USP (SWFI) stop/prevent the of bacela Bacteriostatic Water for Injection USP growth -  Sterile water for irrigation 14 Vehicles for Injection - Cont. 1 water & I water-missible solvent ~  Water-miscible vehicles: - - water -when high ↳ Is too content  To increase drug solubility and/or reduce hydrolysis - - - – Stability! A ~ reduce solubiIHy  Ethanol, propylene glycol, polyethylene glycol 300  Nonaqueous vehicles:  Pure, sterile pyrogen free particulate free - - , ,  Must remain clear on cooling to 10oC - -  Use is confined to IM injections (intramuscular) strictly prescribed -  Can be irritating and allergic reactions can occur - -  Examples: Peanut oil – Dimercaprol; Cotton seed oil – Estradiol cypionate; Castor oil – Estradiol valerate 15 Buffers (Added to control slight change in pH to ensure produce & API is stable)  Maintains pH, stability and prevent degradation - - -  Consider: chemical interactions, effective pH range  Blood pH: 7.4  pH > 9.0, tissue necrosis (cell death)  pH < 3.0 extreme pain, phlebitis (inflammation of cells) - 16 Antioxidants functions by I :  Prevent the oxidization process by either: 3  Blocking the oxidization process - Sat selfa nu  Being oxidized faster than the drug - -  Examples (water-soluble): ascorbic acid, sodium sulfite, sodium bisulfite  Examples (oil-soluble): butylated hydroxytoluene and hydroxyanisole  Air is displaced with inert gas (N2) to prevent chemical - - reactions Coxidation) ↳ need to minimise O2 & Some O2 are dissolved in solvent 17 Antibacterial Agents  Prevent microbial growth and multiplication - -  Use limited concentration of antibacterial agents -  Mercury reagents e.g. Phenylmercuric nitrate 0.01%  Chlorobutanol, Phenol or cresol 0.5%  Effectiveness varies with formulation  Refrigeration slows the growth, but does not prevent it! - 18 Antibacterial Agents Testing  To determine the effectiveness of an antimicrobial system for a parenteral: 1. Inoculums containing a known number of organisms - (Candida albecans, Aspergillus niger, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus) is added & mix well - 2. Incubate at 32oC & then examine - -  Result: Adequate if no significant increase in - microorganisms ↳ Effective aribacterial agent added * If there's increase : Aubacterial Agent that was added is NOT effective 19 Tonicity Agents (Added↳ to ensure cell does not expand shin ! to maintain volume of cell  Routes that require isotonicity: intrathecal, intraarticular, - intradermal  Reduce pain of injection and tissue irritation -  Reduce hemolysis of blood cells (reduce breage of cell)  Prevent electrolyte imbalance  Can include buffers: Eg  : Sodium chloride (0.9%), potassium chloride, dextrose - (5.5%), mannitol, sorbitol, lactose 20  structure maintain Protectants (sugars added to protect certain type of API) !  Protectants are sugars (e.g.: glucose, trehalose, - lactose) that form glasses at low temperatures  Used to maintain the chemical and physical stability of drugs that are frozen and freeze-dried: protein drugs - - - and some peptide antibiotics - & - Inactive structure change : ↓ to use this : add sugar to maintain ↳ than & Inject 21 Other Prenteral Adjuncts  Suspending or viscosity increasing agents:  Sodium carboxymethyl cellulose, gelatin, methylcellulose  Chelating agents: enhance solubility/chemical stability  ethylenediamine tetraacetic acid (0.01-0.075%)  Inert gases (added to replace be inside bottle to prevent oxidation)  N2 (gentamicin sulfate injection)  CO2 (sodium bicarbonate injection)  Adjuncts influencing solubility:  Sodium benzoate to solubilize caffeine  Ethylene diamine to solubilize theophylline 22 Parenteral Formulations 23 Parenteral Formulations  Examples: (API) CAPK) 24 Industrial Preparation of Parenteral Products  Must follow aseptic technique: prevent contamination of - - - - materials, instruments, utensils, containers, during handling  Aseptic procedures use:  UV lights, filtered air supply, sterile equipment (before usage) - need to be maintain 25 Packaging of Injections  Packaged to maintain product sterility until time of use -  Containers must not interact with the preparation -  Types of containers: Glass and plastic polymers:  Ampoules, vials, pre-filled syringes  Rubber closures composition  Rubber (natural) neoprene or butyl base polymer  Plastic bags >- then inject & share  Dual chamber vials - # Exceiperts & API  Cartridges and delivery pens solve ↓ 26 Labeling and Storage of Injections  Labels must contain:  Name of product  Lot number  Expiration date  % of drug or amount of drug in specified volume  Route of administration (muscies velns blood stream soluts, , , , )...  Manufacturer and distributor  Name and quantity of all added substances  Storage: room temperature of fridge (vaccines, insulin) 27 Parenteral Incompatibility  Physical: visible change in solution appearance, e.g., - precipitation, color, gas formation  Chemical: chemical change resulting in either toxicity or therapeutic inactivity which is not always visible -  Hydrolysis, complexation, oxidation, photolysis & API reacted  Therapeutic: change in activity with light  e.g. cortisone antagonizing heparin  Preventing or minimizing incompatibilities:  Control of all factors which lead to incompatibilities - - - 28 Available Injections  Hundreds of injections available  Small volume parenterals (SVP) (25-50 ml)  Can be in solution or suspensions, emulsions, solids - - - -  Premixed, ready to use: require little or no manipulation  Little wastage  Do not offer flexibility in quantity/concentration - - -  Some products require thawing – microwave  Large volume parenterals (LVP)  Flexible but requires manipulation Homantall strility) - 29  Cusually NO API) - to replenish nutitional materials Large-Volume Parenterals (LVP’s) (invelns)  Usually administered by intravenous infusion to replenish - body fluids, electrolytes, or to provide nutrition. Volume: 100ml-1L or more per day  These solutions should not contain bacteriostatic or pharmaceutical additives. They contain:  Electrolytes, carbohydrates  Nutritional: proteins, fatty emulsions 3 to Marian body system  LVP employed for: ① Maintenance therapy: ② Replacement therapy 30 Large-Volume Parenterals (LVP’s): Maintenance Therapy  For patients entering or recovering from surgery and for - those who are unconscious and unable to take nutrients - -  Total parenteral nutrition (TPN) provided if oral feeding must be differed for periods of weeks or longer to provide ↳ all essential nutrients to minimize tissue breakdown and maintain normalcy  Total nutrient admixtures (TNA) include all substrates necessary for nutritional support (carbohydrates, proteins, - - fats, electrolytes and trace elements  Nutrients are mixed in a single intravenous bag for - convenient administration - 31 Large-Volume Parenterals (LVP’s): Replacement Therapy  Heavy loss of water and electrolytes need to be replaced:  Water requirements: 25-40mL/Kg  Electrolyte requirements: K 100mEq; Na 135-170mEq  Caloric requirements: 5% dextrose  For patients with: Vomiting, diarrhea, burns, AIDS … - Clost fluids & nutrests & electrolytes 4. : need LVP to replenish those body fluids that are lost 32 Irrigation Solutions  Irrigation solutions: Intended to bathe or wash wounds, surgical incisions, or body tissues (for transplant) -  Subjected to same stringent standard as for parenteral - preparations ↳ Pyrogen free particulate free strile , ,  Example: Sodium chloride irrigation, USP 0.9% NaCl - used to to wash wounds and employed as enema 33 Dialysis Solutions  Dialysis is separation of substances from one another in solution by taking advantage of their differing diffusibility - through membranes -  Example: Peritoneal dialysis solutions used to remove toxic substances excreted by kidneys  Commercially available solutions contain:  Dextrose, vitamins, electrolytes, amino acids 34