PARENTERALS

PARENTERAL
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.

Based on the route of administration, sterile products are classified into:

1. 2. 3. 4.

Parenteral preparations Ophthalmic preparations - for the eye Otic preparations - for the ear Nasal preparations - for the nose & throat 5. Irrigating solutions - for washing wounds or abraded mucous membrane

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

ROUTES

PARENTERALS

Injections- (1874) Earliest injectible drug: Mophine solution Preparation intended to be administered parenterally Sterility is important because they are placed in direct contact with internal body tissues or fluids, Sterile Pyrogen- free

Physician Physicians assistant Nurse

PARENTERALS ARE ADMINISTERED BY:

PARENTERALS ARE ADMINISTERED AT:

Hospitals Clinics Extended care facilities

Antirheumatic injectables
Brand Name: Enbrel Generic name:: Etanercept Manufacture: Immunex Form::Injectable

Recommended initial dose: 25mg (1 vial) twice a week

injected subcutaneously

Botulinum toxin
Brand name: Botox Generic name: Clostridium botulinum ( type A neurotoxin
complex) Form: Powder for solution for injection

Botulinum toxin
Brand name: Myobloc Generic name: Botulinum toxin Type B Form: Injection, solution [single-dose vial]: 5000 units/mL (0.5 mL, 1
mL, 2 mL) [contains albumin 0.05%]

Intravenous Route (IV)

Intravenous Route (IV)

Advantage: May be a life-saving procedure because of the placement of the drug directly into the circulation and the prompt actions which ensues. Disadvantage: Once the drug administered, it cannot be retrieved. In the case of adverse reaction to the drug, for instance, the drug cannot be easily removed from the circulation. Precautions: Strict aseptic precautions must be taken at all times to avoid risk of infection. The syringes and needles used must be sterilized and to the point of entrance must be disinfected to reduce chance of carrying bacteria from the skin into the blood via the needle

Intravenous Route (IV)

Flow Rates: Generally, the flow rates of IV are expressed in mL/hour, Range from 42 to 150 mL/hour. Lower rates are used for keep-open (KO, KVO) Great care must be taken to prevent overdosing or underdosing. Example: Metoprolol (beta blocker) 3 bolus injections of 5 mg each at about 2-minute intervals; oral dosing (100 mg/day)

Intravenous Route (IV)

NOTE: Not only are the injectable solutions sterile, syringes, needles must also be disinfected to reduce the chance of carrying bacteria A backflow of blood into the administration set or syringe indicates proper placement of the needle in the vein Intravenous drugs ordinarily must be aqueous solution; they must mix with the circulating blood and not precipitate from solution. Such an event can lead to pulmonary micropillary occlusion and blockage of blood flow.

Intravenous Route (IV)

Intravenous fat emulsions
Intralipid, 10,20,30% Clintec Liposyn 11,10, 20% Abott Liposyn 111, 10,20,30% as a source of calories and essential fatty acids for patients requiring parenteral nutrition for extended period, usually more than 5 days. The product contains up to: 30% soybean oil emulsified with eggyolk phospholipids in a vehicle of glycerin in water injection

INTRAVENOUS

Different lengths of needles

Intravenous Route (IV)

Hazard Of Intravenous Injection

The possibility of thrombus formation induced by the touching of the wall of the vein by the catheter or needle. Thrombus is a blood clot formed within the blood vessel (or heart) due usually to a slowing of the circulation or to an alteration of the blood or vessel wall. Once such a blot circulates, it becomes an Embolus carried by the blood stream until it lodges in a blood vessel, obstructing it, and resulting in blockage or occlusion referred to as an Embolism.

INTRASYNOVIAL / INTRASPINAL

INTRATECAL: SPINAL FLUID

INTRAARTERIAL: ARTERIES

Intravenous Route (IV)

Example: Automated IV delivery system - Self administration analgesics Advantages:

1. Patient Controlled Analgesia (PCA) used to control pain 2. Allows greater degree of ambulation and independence 3. Typical PCA contains analgesic drug, syringe and programmable electromechanical unit, which might be compact enough to be worn on a belt or carried in a pocket Example: WalkMed PCA 4. Ability to provide constant and uniform analgesia

5. Can prevent pharmacokinetics and pharmacodynamic differences between patients from interfering with the effectiveness of analgesia 6. Also permits patients to medicate themselves when there is breakthrough pain. 7. Minimizes various side effects 8. PCA devices can be used for IV, SC or epidural administration 9. These devices are either, demand dosing (fixed dose of drug is injected intermittently) or constant-rate infusion plus demand dosing

Intramuscular (IM)

Intramuscular (IM)

Intramuscular injections of drugs provide effects that are less rapid, but generally of greater duration than those obtained from intravenous administration IM are performed deep into the skeletal muscles. The point of injection should be as far as possible from major nerves and blood vessels.

Injuries to patients from IM injection usually are related to the point at which the needle entered and where the medication was deposited.

Intramuscular (IM)
Such injuries include:
1. 2. 3. 4. 5. 6. 7. Paralysis resulting from neural damage Abscesses Cysts Embolism Hematoma Sloughing of the skin Scar formation Adult upper outer quadrant of the gluteus maximus Infants gluteal area is small, composed primarily fats not muscle, so not recommended Infants and Young children deltoid, muscles of the upper arm or the midlateral muscles of the thigh

Intramuscular (IM)
Volume of Administration: limited : 5 mL in the gluteal region 2 mL in the deltoid of the arm. Injection is 2 to 3 inches deep 20 to 22 gauge needle. To avoid staining: it must be injected only into the muscle mass of the upper outer quadrant of the buttock.

Intramuscular (IM)
The

skin is displaced laterally, then needle inserted and syringe aspirated, and injection performed slowly and smoothly. The needle is then withdrawn and the skin release. This create a Z pattern that blocks infiltration of medication into subcutaneous tissue. The Z-Track Injection techniques is useful for IM injections of medications that stain upper tissue. Examples: Iron dextran injection irritate tissues Diazepam (Valium) by sealing in the lower muscle

Subcutaneous Route (SC)

May be utilized for the injection of small amounts of medication or of drugs beneath the surface of the skin of the 1. upper arm, 2. the anterior surface of the thigh, and the 3. lower portion of the abdomen. The site of injection is usually rotated when injections are frequently given, as with daily insulin injection. The maximum amount of drug given SC is about 1.3 mL Amounts greater than 2 mL will most likely cause painful pressure.

Subcutaneous Route (SC)

Syringes: up to 3 mL capacities Utilizing needles: 24 to 26 gauges SC insulin needles: gauge between 25 to 30 needle length between 5-16 to 5-8 inch. Upon insertion, if blood appears in the syringe, a new site should be selected. Irritating drugs and those in thick suspension may produce induration, sloughing, or abscess and may be painful. Such preparations are not suitable for subcutaneous injection

Intradermal Route

Substances may be effectively injected into the corium, the more vascular layer of the skin just beneath the epidermis. These substances include: diagnostic determinations, desensitization, or immunization. Usual site: anterior surface of the forearm. Needle: A short (3-8 inch) and narrow gauge (23 to 26). is inserted horizontally into the skin with the bevel facing upward. The injection is made when the bevel just disappears into the corium. Volume: Usually about 0.1 mL

Specialized Access
Devices

that provide continued access and reduce pain associated with administration (Repeated injections over time) Several catheters of central venous are used for a variety of parenteral medications. Example: cancer chemotherapy, long term antibiotic therapy, TPN solutions

The

use of indwelling plastic catheters reduces the need for multiple punctures during intravenous therapy. Composed of polyvinyl chloride, Teflon, and Polyethylene, these should be radiopaque to ensure that they are visible on radiographs.

Specialized Access

Usually, these must be removed within 48 hours after insertion. The choice of catheter depends on several factors 1. Length of time of the infusion 2. Purpose of the infusion 3. Condition and availability of the veins Types of Catheter 1. Plain plastic 2. Catheter over needle or outside needle 3. Catheter inside needle

Official 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

Official Types of Injections

3. Drug Injectable Emulsion - Liquid preparations of drug substances dissolved or dispersed in a suitable emulsion medium Example: Propofol

Official Types of Injections

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

Official Types of Injections

INSULIN INJECTION, USP

PROPOFOL

METHYLPREDNISOLONE ACETATE SUSPENSION

Injections

Generally, if a drug is unstable in solution, it may be prepared as a dry powder intended for reconstitution with the proper solvent at the time of administration If the drug is unstable in water, the solvent may be replaced in part or totally by a solvent in which the drug is insoluble If the drug is insoluble in water, an injection may be prepared as an aqueous suspension or as solution in a suitable nonaqueous solvent, such as a vegetable oil If an aqueous solution is desired, a water soluble salt form of the insoluble drug is frequently prepared Aqueous or blood miscible solutions may be injected directly into the blood stream

Injections

Blood immiscible liquids, such as oleaginous injections and suspensions can interrupt the normal flow of blood, and their use is generally restricted to other than intravenous administration Often times long action is desired to reduce the frequency of injections. These long acting injections are called respiratory or depot preparations

Following differences with other preparations

1. Solvents or vehicles used must meet special purity

and other standards assuring their safety by injection 2. The use of added substances, as buffers, stabilizers, and antimicrobial preservatives, fall under specific guidelines of use and are restricted in certain parenteral products. The use coloring agents is strictly prohibited. 3. Parenteral products are always sterilized and meet sterility standards and must be pyrogen free. 4. Parenteral solutions must meet compendial standard for particulate matter. 5. Parenteral products are packaged in special hermetic containers of specific and highly quality.

Following differences with other preparations

6. Each container of an injection is filled to a volume in slight

excess of the labeled size or volume to be withdrawn. This overfill permits the ease of withdrawal and administration of the labeled volumes 7. Parenteral products must be prepared in environmentally controlled areas, under strict sanitation standards, and by personnel specially trained and clothed to maintained the sanitation standards. 8. There are restrictions over the volume of injection permitted in multiple-dose containers and also a limitation over the types of containers (single-dose or multiple- dose) which may be used for certain Injections. 9. Specific powders intended for solution or suspension immediately prior to injection are frequently packaged as lyophilized or freeze-dried powders to permit ease of solution or suspension upon the addition of the solvent or vehicle.

Solvents and Vehicles for Injections

1. Water for Injection, USP This water is purified by distillation or by reverse osmosis. Water for Injection is not required to be sterilized, it must be pyrogen free. 2. Purified water, USP may not contain other substances and meets standard for the presence of total solids 3. Sterile Water for Injection, USP is water for injection which has been sterilized and packaged in single-dose containers of not greater than I L size. as water for Injection, it must be pyrogen free and may not contain an anti-microbial agent or other added substance.

Solvents and Vehicles for Injections

4. Bacteriostatic Water for Injection, USP is sterile water for injection containing one or more suitable anti-microbial agents. it is packaged in pre-filled syringes or in vials containing not more than 30 mL of the water. Label must state, Not for Use in Newborns. Example: benzyl alcohol - not good for neonates and the toxicity of the bacteriostat. 5. Sodium Chloride Injection, USP a sterile isotonic solution of sodium chloride in Water for Injection. It contains no antimicrobial agents

Solvents and Vehicles for Injections

6. Bacteriostatic Sodium Chloride Injection is a sterile isotonic solution of sodium chloride in Water for Injection. It contains one or more suitable antimicrobial agents which must be specified in the label. Sodium chloride concentration is 0.9% to render isotonic solution. It is also used to flush a catheter or IV line to maintain its patency.. Not for Use in Newborns. 7. Ringers Injection, USP is a sterile solution of sodium chloride, potassium chloride, and calcium chloride in water for injection. It is used as electrolyte replenisher and a systemic alkalizer. Lactated R = Na lactate

BACTERIOSTATIC WATER SODIUM CHLORIDE INJECTION, USP; POTASSIUM CHLORIDE

SODIUM CHLORIDE INJECTION, USP

BACTERIOSTATIC WATER FOR INJECTION, USP

STERILE WATER FOR INJECTION, USP

DEXTROSE INJECTION

Characteristics 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

Nonaqueous Vehicles Selected Vehicles must be:

1. 2. 3. 4.

Nonirritating Non toxic in the amounts administered Nonsensitizing It must not exert a pharmacologic activity 5. May not adversely affect the activity of the medicinal agent

Other 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.

Examples of Nonaqueous Solvents

1. 2. 3. 4. 5. 6. 7. 8. Fixed vegetable oils Glycerin Polyethylene glycols Propylene glycol Ethyl oleate Isopropyl myristate Methylacetamide Alcohol

Nonaqueous Vehicles
Examples of Fixed Oils Commonly Used in Injections

1. 2. 3. 4. 5.

Corn Oil Cottonseed seed Oil Peanut Oil Sesame Oil Castor Oil and Olive Oil (occasion)

SOLVENTS AND VEHICLE FOR INJECTIONS

Water for Injection solvent purified by distillation or by reverse osmosis stored in tight container with temperature below or above the range of microbial growth must be pyrogen free

Added Substances

Additives are essential for almost every product to enhance its stability. They must exhibit the following characteristics: 1. Perform its function throughout the useful life of the product 2. Must be non-toxic and non-irritating 3. Must not exert any adverse effect on the product 4. Must be compatible in all components of the formulation 5. Must not interfere with: a. Therapeutic efficacy b. Assay of the active therapeutic compound

Such substances include:

1. 2. 3. 4. 5. 6. 7. 8. Solubilizers Chelating agents Anti-microbial agents Hydrolysis Inhibitors Antioxidants Buffers Tonicity contributors Antifoaming agents

Antifungal/Antibacterial

must be present in adequate concentration at the time of use to prevent the multiplication of microorganism. Examples: agents containing mercury and the cationic, surface active compounds - 0.01%; for agents like chlorobutanol, cresol, and phenol - 0.5%

Antioxidants
Oxidation

is one of the pathways of degradation which can be accelerated during thermal sterilization. To protect a therapeutic agent susceptible to this reaction, antioxidants are required. Example: Sulfur dioxide - 0.2%

Classification of Antioxidants Used In Sterile Products

1. Reducing agents - antioxidants which functions by being preferentially oxidized Examples: ascorbic acid sodium bisulfite metabisulfite thiourea sodium formaldehyde sulfoxylate 2. Blocking agents - antioxidants which block an oxidative chain reaction in which they are not usually consumed Examples: ascorbic acid esters butyl hydroxytoluene (BHT) tocopherols

Classification of Antioxidants Used In Sterile Products

3. Synergists - compounds increase the effectiveness of antioxidants, particularly those blocking oxidative reactions Examples: ascorbic acid citraconic acid phosphoric acid citric acid tartaric acid 4. Chelating agents - those that complex with catalysts which otherwise would accelerate the oxidative reaction Examples: ethylenediaminetetraacetic acid salts 5. Inert gases like nitrogen and carbon dioxide have been used to displace oxygen from a solution and reduce the possibility of oxidative changes in the formulation

Buffers

are added to maintain the required pH for many products; a change in pH may cause significant alterations in the rate of degradation reactions. Changes in pH may occur during storage as a result of: 1. Dissolving of glass constituents in the product 2. Release of constituents from rubber closures or plastic components in contact with the product 3. Dissolving of gases and vapors from the air space in the container or by diffusion through the rubber or plastic component. 4. Reactions within the product

The principal buffer systems used to stabilize pH are the 1. Acetates 2. Citrates 3. Phosphates
Tonicity

Contributors

Compounds contributing to the isotonicity of a product reduce the pain of injection in areas with nerve endings. Buffers may serve as tonicity contributors as well as as stabilizers for the

Containers

Containers for sterile products are made of glass or plastic. Glass is still preferred for injectable products. Glass is composed principally of the silicon dioxide tetrahedron modified physicochemically by such oxides as those of sodium, potassium, calcium, magnesium, aluminum, boron and iron. Two general types of glass (1) soda-lime (2) borosilicate

Containers

Based on its chemical resistance, glass compounds are classified into 4 types: 1. 2. 3. 4. Type I - highly resistant borosilicate glass Type II - treated soda-lime glass Type III - soda lime glass NP (nonparenteral) - general purpose soda-lime glass

Glass containers like ampule cartridges and vials may be manufactured from glass tubings or blow molding.

Rubber closures

are used to seal the openings of catridges, vials and bottles, providing a material soft and elastic enough to permit entry and withdrawal of a hypodermic needle without loss of the integrity of the sealed container. Accessories used in conjunction with closures are aluminum caps with or without flif-off seals.

Examples of Some Injections in Oil

Injections

Oil Peanut Cottonseed Sesame/Castor Sesame Sesame Castor Sesame/Peanut Cottonseed Cottonseed Sesame Sesame

Category Antidote to As ,Au, Hg poisoning Estrogen Estrogen Antipsychotic Antipsychotic Progestin Progestin Androgen Androgen and Estrogen Androgen Andragen and Estrogen

Dimercaprol Injection Estradiol Cypionate Injection Estradiol Valerate Injection Fluphenazine Decanoate Inj. Fluphenazine Enanthate Inj. Hydroxyprogesterone Caproate Progesterone in OilInjection Testosterone Cypionate Testosterone Cypionate and Estradiol Cypionate Testosterone Enanthate Inj. Testosterone Enanthate and Estradiol Valerate

METHODS OF STERILIZATION
Sterilization

defined as the complete destruction or elimination of microbial life. The choice of the most effective sterilization procedure is dependent on: 1. Compatibility of the process with the preparation; (sterilization process must not have significant adverse effect upon the preparation) 2. The successful validation of the process ( the parameters must prove to be lethal to the most resistant spores of microorganism normally encountered)

5 GENERAL METHODS

1. 2. 3. 4. 5.

Steam distillation Dry-heat sterilization Sterilization by filtration Gas sterilization Sterilization by ionizing radiation

2 MAIN DIVISIONS OF STERILIZATION

1. Physical Processes of Sterilization A. Thermal Method Microorganisms are killed by heat by what is thought to be coagulation of the protein of a living cell. The lethal effectiveness of heat is dependent on: 1. The degree of heat 2. The exposure period 3. The moisture present

Steam sterilization is conducted in an

autoclave and employs steam under pressure The usual steam pressures, the temperatures obtainable under these pressures, and the approximate length of time required after the system reaches the indicated temperatures are as follows: 1. 10 pounds pressure (115.50C), for 30 min. 2. 15 pounds pressure (121.50C), for 20 min. 3. 20 pounds pressure (126.50C), for 15 min.

2 MAIN DIVISIONS OF STERILIZATION

Dry-Heat Sterilization usually carried out in sterilizing ovens specifically designed for this purpose. The ovens may be heated either gas or electricity and generally thermostatically controlled. conducted at temperatures of 1600C to 1700C for periods not less than 2 hours.

B. Nonthermal Methods
1. Ultraviolet light - is commonly employed to aid in the reduction of airborne contamination and to attempt to sterilize surfaces within the processing environment. The germicidal light produced by mercury vapor lamps is emitted at a wavelength of 2537 Angstrom units (253.7 millimicrons) The lethal mechanism of UV light works when this energy is absorbed by orbital electrons within the molecules of the microorganisms or of their essential metabolites causing excitation and alteration of activity. Thus the organism dies or is unable to reproduce.

2 MAIN DIVISIONS OF STERILIZATION

2. Ionizing Radiations - are highly radiations emitted from radioactive isotopes such as cobalt-60 (gamma rays) or produced by mechanical acceleration of electrons to very high velocities and energies (cathode rays, beta rays). Ionizing radiations destroy microorganisms by stopping reproduction as a result of lethal mutations.

3. Filtration - This is a nonthermal method for

the sterilization of select solutions by removing microorganisms from the solution while permitting the passage of all the desired components of the solution and imparting no undesirable components from the filter. They are available in pore sizes from 14 to 0.025 um. The size of the smallest particle visible to the naked eye is about 40 um, a red blood cell is about 6.5 um, the smallest bacteria, about 0.2 um, and a polio virus, about 0.025 um

2 MAIN DIVISIONS OF STERILIZATION

2. Chemical Processes of Sterilization A. Gas Sterilization - Ethylene oxide believed to exert its lethal effect upon microorganisms by alkylating essential metabolites, affecting particularly the reproductive process. Ethylene dioxide sterilization is the acceptable practical method for sterilizing plastic. Other gases used are beta propiolactone, formaldehyde and sulfur dioxide

2 MAIN DIVISIONS OF STERILIZATION

B. Surface Disinfection Disinfectants do not sterilize a surface. However, as adjuncts to thoroughly cleaning of surfaces, disinfectants properly used may be expected to provide an aseptic condition of the surfaces involved

Validation of Sterility

Regardless

of the method of sterilization employed, Pharmacutical preparations must undergo sterility tests to confirm the absence of microorganisms. A biologic indicator is characterized preparation of specific microorganisms resistant to a particular sterilization process

2 main forms
1. Spores are added to a carrier, as a strip of filter paper, packaged to maintain physical integrity while allowing the sterilization effect. 2. The spores are added to representative units of the product being sterilized, with sterilization assessed based on these samples In moist heat (steam) - Bacillus stearothermophilus In dry heat - Bacillus subtilis In ionizing radiation - Bacillus pumilus, stearothermophilus, subtilis

Pyrogens and Pyrogen Testing

Pyrogens

are fever producing organic substances arising from microbial contamination and responsible for many of the febrile reactions which occur in patients following injections. Are lipid substances associated with a carrier molecule which is usually a polysaccharide but may be a protein.

2 Official Tests for Detecting and Measuring Pyrogens

1. Bacterial Endotoxins Test

Using Limulus Amebocyte Lysate (LAL) which has been obtained from aqueous extracts of the circulating amebocytes of the horseshoe crab, Limulus polyphemus, and which has been prepared and characterized for use as an LAL reagent for gel-clot formation. The procedure include incubation for a preselected time of reacting endotoxins and control solutions with LAL Reagent and reading of the spectrophotometer light absorbance at suitable wavelength

2 Official Tests for Detecting and Measuring Pyrogens

2. Pyrogen Test
The test involves measuring the rise in temperature of rabbits following the intravenous injection of a test solution and is designed for products that can be tolerated by the test rabbit in a dose not to exceed 10 mL per Kg injected intravenously within a period of not more than 10 minutes If no rabbit shows an individual rise in temperature 0.60C or more above its respective control temperature, and if the sum of the 3 individual maximum temperature rises does not exceed 1.400 C, the product meets the requirements for the absence of pyrogens.

Depyrogenation Method are as follows: 1. Adequate washing with detergent treatment followed by dry heat sterilization is recommended for glasswares and equipment. Optimum temperature is 2500C for 45 minutes. 2. Distillation is the most reliable method of eliminating pyrogens from water. Pyrogenic substances are not volatile and thus will remain in the distilland. 3. Removal of pyrogens by select adsorbents has limited use because of the concurrent phenomenon of adsorption of solute ions of molecules. It is of interest in the production of antibiotics where heavy pyrogen contamination results from fermentation.

PRODUCTION of a sterile preparation

consists

1. 2. 3. 4. 5.

of the following steps: Compounding Filtration Filling Sealing Sterilization

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

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.

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.

Containers

should be sealed in an aseptic area adjacent to the filling machine. Ampuls are sealed by heating with a high temperature gas-oxygen flame to form 1. Tip-seals: those made by melting sufficient glass at the tip of the ampul neck to form a bead of glass and close the opening 2. Pull-seals: those made by heating the neck of a rotating ampul below the lip, then pulling away the tip to form a small, twisted capillary just prior to being melted closed.

A leakers test
is

a useful method for evaluating the efficiency of the sealing process. the test consists of immersing completely the sterile sealed ampuls in an aqueous dye bath (0.5 to 1.0% of methylene blue) within a vacuum chamber. ss negative pressure of 27 inches Hg or more is created, a tiny drop of dye solution can penetrate an opening of an incompletely sealed ampul. the colored ampuls are sorted out during washing and 100% inspection that follows after.

Examples of Sterile Drugs prepared and packaged without the presence of phamaceutical additives as buffers, preservatives, stabilizers, tonicity agents, and other substances 1. 2. 3. 4. 5. 6. 7. 8. 9. Sterile Ampicillin Sodium Sterile Ceftazidime Sodium Sterile Kanamycin Sulfate Sterile Penicillin G Banzathine Sterile Tobramycin Sulfate Sterile Ceftizoxime Sodium Sterile Cefuroxime Sodium Sterile Nafcillin Sodium Sterile Streptomycin Sulfate

Examples of Sterile drugs formulated with pharmaceutical additives and intended to be reconstituted prior to Injection
1. Cephradine for Injection 2. Dactinomycin for Injection 3. Erythromycin Lactobionate for Injection 4. Oxytetracycline Hydrochloride Injection 5. Nafcillin Sodium for Injection 6. Hydrocortisone Sodium Succinate for Injection 7. Cyclophosphamide for Injection 8. Hyaluronidase for Injection 9. Mitomycin for Injection 10. Penicillin G Potassium for Injection 11. Vinblastine Sulfate for Injection.

Containers
1. Mix-O-Vial - that incorporates the cover as part of the plunger. Once mixed, the small circle of plastic that covers the injection site is removed. This reduces the touch contamination 2. Add-Vantage System IVPH - is other example of ready-to-mix sterile IV product designed for intermittent IV administration of potent drugs that do not have long term stability in solution. Two components: (a) A flexible plastic IV container partially filled with diluent (b) Glass vial of powdered or liquid drug

The

vials containing the medication and the piggybacks (50-250 mL of Dextrose 5% in Water Injection) or Normal Saline Solution are specially designed to be used together. The ADD-Vantage System can be used within 30 days from the date that the diluent container was removed from the overwrap.

Containers
3. Monovial Safety Guard - This is new system integrated device (drug transfer mechanism) with a protective shield surrounding the attached transfer needle. The reconstitution and transfer of the drug into an infusion bag is accomplished safely, quickly, and necessitates fewer materials. The needle is inserted into the port of the infusion bag and then the transfer set is pushed down toward the vial until a Click is heard. With Monovial upright, the infusion bag is squeeze several times to transfer liquid into the Monovial. The Monovial is then shaken to reconstitute the drug. It is then inverted, the minibag is squeezed and release to transfer the drug back into the infusion bag. This process is repeated until the vial is empty.

Packaging, Labeling, and Storage of Injections Containers for injections, including closures, must not interact physically and chemically with the preparation. Single-dose container - A single dose container is a hermetic container holding a quantity of sterile drug intended for parenteral administration as a single dose, and which when opened cannot be re-sealed with assurance that sterility has been maintained. Multiple-dose container - A multiple-dose container is a hermetic container that permits withdrawal of successive portions of thecontents without changing the strengths, quality, or purity of the remaining portion. Note: Recall type I,II,III containers

The Labels on containers of parenteral products must state: 1. The name of the preparation 2. For liquid preparation, the percentage content of the drug or amount of the drug; for dry preparation - the amount of the active ingredient present and the volume of liquid to be added to the dry preparation to prepare a solution or suspensions. 3. The route of administration 4. Statement of storage conditions and expiration 5. The name of the manufacturer and distributor 6. The identifying lot number

General Precautions required with the use of microwave ovens for thawing frozen premixed products include
1. Being aware that the possibility of radiation leakage does exist. However, manufacturers of microwave ovens are required by law to comply with federal standards 2. Safeguarding pharmacy personnel who are exposed to these ovens, especially those with cardiac pacemakers. 3. The possible leaching of rubbers material when the rubber material on the container is exposed to microwave heating. 4. A possible explosion that may result from the increase in internal pressure as a result of placing a closed or sealed container into the microwave oven. 5. Developing protocols to ensure that the final solution temperature does not exceed room temperature

Examples of some Injections Usually Package and Administered in Small Volume 1. Butorphanol Tartrate Injection - Narcotic Agonist- Antagonist Analgesic 2. Chlorpromazine HCl Injection - Antipsychotic drug with antiemtic 3. Cimetidine HCl Injection - Histamine H2 antagonist 4. Dalteparin Sodium Injection - Prophylaxis against deep vein thrombosis 5. Dexamethasone Sodium Phosphate Injection Glucocorticoids 6. Digoxin Injection - Cardiotonic

Examples of some Injections Usually Package and Administered in Small Volume 7. Dihydroergotamine Mesylate Injection - Alpha-adrenergic blocking agent 8. Diphenhydramine HCl Injection - An ethanolamine, non selective antihistamine 9. Furosemide Injection - Loop diuretic 10. Granisetron HCl Injection - Prevention of nausea and vomiting 11. Heparin Sodium Injection - Anticoagulant (IV or SubQ) 12. Hydromorphone HCl Injection - Narcotic analgesic

Examples of some Injections Usually Package and Administered in Small Volume

13. 14. 15. 16. 17. Ibutilide Fumarate Injection - An antiarrhythmic drug Iron Dextran Injection - Hematinic agent Isoproterenol HCl Injection - Adrenergic (bronchodilator) Ketorolac Tromethamine Injection - NSAID Lidocaine HCl Injection - Cardiac depressant as an antiarrhythmic 18. Magnesium Sulfate Injection - Anticonvulsant/Electrolyte 19. Meperidine HCl Injection - Narcotic analgesic 20. Metoclopramide Monohydrochloride Injection - Gastrointestinal stimulant

Examples of some Injections Usually Package and Administered in Small Volume

22. Midazolam HCl 22. 23. 24. 25. 26. 27. 28. 29. - Short acting benzodiazepine CNS depressant Morphine Sulfate injection - Narcotic analgesic Naloxone HCl Injection - Narcotic antagonist Nalbuphine HCl Injection - Narcotic Agonist-Antagonist Analgesic Oxytocin Injection - Oxytoxic Phenytoin Sodium Injection - Anticonvulsant Phytonadione Injection - Vitamin K (prothrombogenic) Procaine Penicillin G Injection - Anti-infective Prochlorperazine Edisylate Injection - Antidopaminergic

Single-dose unit

2 mL Single-dose vials BUTORPHANOL TARTRATE INJECTION 8 mL Multi-dose vials

8 fl oz

TAGAMET 300 mg/2 mL Product Classification: RX Manufacturer: SMITHKLINE BEECHAM PHARM FUROSEMIDE INJECTION HEPARIN SODIUM INJECTION

LANOXIN

BENADRYL

CIMETIDINE HCL INJECTION>>>>

SODIUM BICARBONATE INJECTION

>>>IRON DEXTRAN INJECTION

LIDOCAINE<< HCL INJECTION

MIDAZOLAM HCL INJECTION>>>>

>>PROCAINE PENICILLIN G INJECTION

>>NALBUPHIN HCL INJECTION

MAGNESIUM SULFATE

PHYTONADIONE

Examples of some Injections Usually Package and Administered in Small Volume

30. Propranolol HCl Injection - Beta adrenergic receptor blocking agent 31. Sodium Bicarbonate Injection - Electrolyte 32. Sumatriptan Succinate injection - treat acute migraine attacks 33. Verapamil HCl Injection - Calcium channel blocking agent

INSULIN
1. Insulin Injection (regular) Insulin Injection is a sterile aqueous solution of insulin. It is prepared from beef or pork pancreas or both or through biosynthetic means (Human Insulin). With apH of 2.8 to 3.5. Insulin Injection is prepared to contain 100 or 500 USP Insulin Units in each mL. Expiration: Not to be later than 24 months after the date of distribution. Preservative: Glycerin (1.4 to 1.8) for stability Phenol or Cresol (0.1 to 0.25%) Storage: Cold place, preferably the refrigerator

2. Human Insulin It is produced by utilizing a special nondisease-forming laboratory strain of Escherichia coli and recombinant DNA technology. Two formulations: (1) Neutral Regular Human Insulin (Humulin R) - consists of Zinc-insulin crystals in solution. It has a rapid onset of action and relatively short duration of action (6 to 8 hours); (2) NPH Human Insulin (Humulin N) - is a turbid preparation that is intermediate acting, with a slower onset of action and longer duration of action (slightly less than 24 hours) than regular insulin

3. Lispro Insulin Solution

Insulin solution consists of Zinc-insulin lispro crystals dissolved in a clear aqueous fluid. It is created when the amino acids at positions 28 and 29 on the Insulin Bchain are reversed Compared to regular insulin, however, peak serum levels of lispro insulin occur earlier, (within 0.5 to 1.5 hours) are higher, and are shorter acting ( 6 to 8 hours) Lispro insulin are administered fifteen minutes before meals has decreased the risk of hypoglycemic episodes and improve postprandial glucose excursions when compared to conventional regular insulin. Storage: Refrigerator; room temperature - 28 days Note: If accidentally frozen, it should not be used

4. Isophane Insulin Suspension (NPH Insulin)

Is a sterile suspension, in an aqueous vehicle buffered with dibasic sodium phosphate to between pH 7.1 and 7.4, of insulin prepared from zinc-insulin crystals modified by the addition of protamine so that the solid phase of the suspension consists of crystals composed of insulin, zinc, and protamine. Protamine is prepared from the sperm or the mature testes of fish belonging to the genus Oncorhynchus. Expiration date: 24 months Dosage: dosage range subcutaneously is 10 to 80 USP Units NPH used in some product names stands for Neutral Protamine Hagedorn; the pH is 7.2 and developed by Hagedorn. The term isophane is based on the Greek: iso and phane, meaning equal and appearance and refers to equivalent balance between the protamine and insulin.

5. Isophane Insulin Suspension and Insulin Injection A premixed formulation of of isophane insulin suspension and Insulin injection. 2 Formulations: 1. Humulin 70/30 - combination that consists of 70% isophane insulin suspension and 30% insulin injection 2. Humulin 50/50 - combination that consists of 50% isophane insulin suspension and 50% insulin injection They contain zinc of 0.01 to 0.04 mg/100 units. Neutral in pH and phosphate buffered Preservatives: m-cresol and phenol

6. Insulin Zinc Suspension

modified by the addition of zinc chloride so that the suspended particles consists of a mixture of crystalline and amorphous insulin in a ratio of approximately 7 parts of crystals to 3 parts of amorphous material. Buffered to pH 7.2 to 7.5 with sodium acetate: 0.7% sodium chloride for tonicity; 0.10% methylparaben as preservatives Expiration: 24 months after the immediate container was filled. Storage: Refrigerator with freezing being avoided

7. Extended Insulin Zinc Suspension

Is a sterile suspension of zinc insulin crystals in an aqueous medium buffered to between pH 7.2 and 7.5 with sodium acetate. Present also are 0.7% sodium chloride for tonicity and 0.1% methylparaben as preservatives Dosage: The usual dosage range is 10 to 80 USP Units Expiration: 24 months after the immediate container was filled

8. Prompt Insulin Zinc Suspension The sterile suspension of insulin in Prompt Insulin Zinc Suspension is modified by the addition of Zinc chloride so that the solid phase of the suspension is amorphous The suspension is available in 100 USP Insulin Units per mL in vials of 10 mL Expiration: not more 24 months

9. Insulin Infusion Pumps

Insulin infusion pumps allow the patients to achieve and maintain blood glucose at near-normal levels on a constant basis. The main objective of pump therapy is the strict control of the blood glucose level between 70 to 140 mg/dL These systems utilize microcomputers to regulate the flow of insulin from a syringe attached to a catheter (usually 18 gauge) connected to a 27 to 28 gauge needle inserted in the patient. The insulin may be delivered SubQ, IV, IP Patients who used infusion pumps for the continuous subcutaneous administration of insulin may develop hard nodules at the site of injection

10. Humalog Mix

Manufactured

premix insulin consisting lispro and neutral protamine lispro (NPL) in afixed ratio Humalol Mix 50/50 consists of 50% insulin NPL suspension and 50% insulin lispro injection Humalog Mix 75/25 contains 75% insulin NPL suspension and 25% insulin lispro injection It is estimated that these premixed combinations are used by more than 40% of diabetes patients who inject insulin twice daily

11. Insulin Glargine

It is a long acting (up to 24 hours) basal insulin preparation intended for once daily subcutaneous administration at bedtime in the treatment of type 1 diabetes mellitus in adult and children In can be used by adults with type 2 diabetes who require long-acting insulin It is created when the amino acids at position 21a of human insulin are placed by glycine and 2 arginines are added to the C terminus of the B chain

Types of Insulin: Approximate effect/action *

Onset Characteristics Peak Duration

Short/Fast-Acting 5 - 30 mins (clear)

IntermediateActing (milky) 1 - 2 hrs

1 - 3 hrs
4 - 12 hrs

4 - 8 hrs
16 - 24 hrs

Premixed (Short & Intermediate)

Long-Acting (milky)

1/2 hr
4 hrs

2 - 12 hrs
8 - 24 hrs

16 - 24 hrs
28 - 36 hrs

Ins ulin Act iv it y Prof ile s a nd Comp at ib ilit y Insulin Preparat ions mix ed wit h Rapid act ing Insulin I nj (reg ula r) Insulin Z inc Lispro Ins ulin Soln Int erm ediat e Isophane Insulin Suspension (NPH) Insulin Zinc Suspension(lent e) 1 t o 2.5 Long act ing PZI (Prot amine Zinc Insulin) 4 to 8 Ext ended Insulin Zinc Isophane Ins ulin Suspensio n Pre m ix ed 50 % and Insulin Inj 5 0 % insulin Isopha ne Ins ulin Susp. 70 % and Insulin Inj, 3 0 % 0.5 2 to 12 1 8 to 24 regula r, NPH 4 to 8 1 4 to 24 10 t o 3 0 36 >36 regula r regular, sem ilent e 7 to 15 24 regula r, semile nt e 1 to 1 .5 4 to 12 24 regula r 0.5 t o 1 8 t o 12 1 t o 1.5 5 to 10 12 to 1 6 all Lent e Prompt Onset (hr) Peak (hr) Durat ion (hr) Compat ible

Suspension(sem ile nt e) 0.2 5 0 .5 t o 1.5 6 to 8 Ult rale nt e, NPH

Ex amples of Some Inject ions Administ ered in La rge V olume by IV t hat may be Administ ered in V olumes of 1 Lit er or More, Alone, or Wit h Ot her Drugs Added

Inject ion

Usual Cont ent

Cat egory / Comment s

A mino A cid Inj ect ion 3 .5,5 ,5 .5 ,7,8 .5 ,1 0 %cryst all ine ami no Flu id / Nut rient repleni she r acid s wit h or wit hou t varyin g concent rat i ons of elect ro lyt es or g lycer in Dext rose Inj ect ion,USP 2.5 ,5 ,1 0 ,2 0% dext rose, ot her st rengt hs Flu id/ Nut rient repleni she r

Dext rose and sod iu m Dex t rose var yi ng f rom 2 .5 t o 1 0% and Flu id/ Nut rient / Elect rolyt e chl or ide Inj ect ion,USP sodiu m chlo ri de f rom 0 .11 (1 9 mEq Na) elect roly t e t o 0.9 % (1 5 4 mEq sodium) M annit ol Inject ion, USP 5,10,15,20 and 25 % mannit ol f unct ion det erminat io ns; diuret ic. Fluid/ Nut rient Ringers Inject ion, USP 1 47 mEq sodium, 4 mEq pot assium calcium, and 1 56 mEq chloride/ lit er Diagnost ic aid in re na l

Fluid/ e lect roly t e

Lact at ed Ringe rs 2.7 mEq calcium, 4 mEq pot assium, Sy st emic alk alinize r; Inject io n, USP 1 30 mEq sodium a nd 2 8 mEq f luid and elect ro ly t e lact at e per lit er replenishe r Sodium Chloride USP vehicle 0 .9 % sodium Chloride Fluid and e lect roly t e Inject ion, reple nishe r, isot onic

INSULIN INJECTION SITES

Large 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

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.

 Maintenance

Therapy

Is given to the patient being maintained on parenteral fluids only several days, simple solutions providing adequate amounts of water, dextrose and small amounts sodium and potassium generally suffice. Total Nutrient Admixtures also may be given (TNA) include all substrate necessary for nutritional support ( carbohydrates, protein, fat, electrolytes, trace elements and others). These admixtures are very useful for patients undergoing chemotherapy, and for gastrointestinal patients, and anorexic patients

Replacement Therapy

Is given to the patient in which there is heavy loss of water and electrolytes, as in severe diarrhea or vomiting, greater than usual amounts of these materials may be initially administered and maintenance therapy provided. Patients with Crohns disease, AIDS, burn patients, or those experiencing trauma are candidates for replacement therapy.

Water Requirement
The daily water requirement is that amount needed to replace normal and expected losses. Normal requirement adult -25 to 40 mL/kg of body weight or an average of about 2,000 mL per square meter of body surface area

Estimate guidelines in normal daily requirement for water

1. <10 kg: 100 mL/kg/day 2. 10-20kg: 1000 mL plus 50 mL/kg/day for weight over 10 kg 3. >20 kg to maximum of 80 kg: 1500 mL Plus 20 mL/kg/day for weight over 20 kg

Electrolyte Requirement
1. Potassium - important for cardiac and skeletal muscle function. The usual daily intake is about 100 mEq and the usual daily loss is about 40 mEq

Potassium can be lost through:

excessive perspiration, repeated enemas, trauma (such as severe burns), uncontrolled diarrhea, diseases of intestinal tract, surgical operations and others.

Low potassium levels - Hypokalemia, can lead to death Symptoms of potassium loss :weak pulse, faint heart sounds, falling blood pressures and generalized weakness
Excess potassium is not good either : Hyperkalemia can cause kidney failure Symptoms : diarrhea, irritability, muscle cramps, and pain

2. Sodium - is vital to maintain normal extracellular fluids.

Average daily intake of sodium: 135 to 170 mEq (8 to 10 g of Sodium chloride) Sodium loss/deficit: 3 to 5 g sodium chloride (51 to 85 mEq of sodium) is administered daily Symptoms: excessive sweating, fatigue, muscle weakness, convulsions Symptoms (excess): Dry, sticky mucous membranes, flushed skin, elevated body temperature, lack of tears, and thirst

3. Chloride - the principal anion of the extracellular

fluid usually paired with sodium. Chloride is also important for muscle contraction, balancing the fluid levels inside and outside the cells and maintaining the acid-base balance of the extracellular fluid. Caloric Requirements Basic caloric requirements may be estimated by body weight; in the fasting state, the average daily loss of body proteins is approximately 80g/day for a 70 kg man. Daily ingestion of at least 100 g of glucose reduces this loss by half. Generally patients requiring parenteral fluids are given 5% dextrose to reduce caloric deficit

Parenteral

hyperalimentation

This is the infusion of large amounts of basic nutrients sufficient to achieve active tissue synthesis and growth. It is employed with a long term intravenous feeding of protein solutions containing high concentration of dextrose (approximately 20%), electrolytes, vitamins, and sometimes insulin.

Components of Parenteral Nutrition Solutions

Electrolytes 1. Sodium. 25 mEq 2. Potassium .. 20 mEq 3. Magnesium 5 mEq 4. Calcium .. 5 mEq 5. Chloride .. 30 mEq 6. Acetate 25 mEq 7. Phosphate .. 18 mM

Vitamins

Vitamin A 3300 I.U. Vitamin D 200 I.U. Vitamin E 10 I.U. Vitamin C 100 mg Niacin 40 mg Vitamin B2 3.6 to 4.93 mg

Vitamin B1 3 to 3.35 mg Vitamin B6 4 to 4.86 mg Pantothenic Acid 15 mg Folic Acid 400 mcg Vitamin B12 5 mcg Biotin 60 mcg

Components of Parenteral Nutrition solutions Amino Acids: Essential Amino Acids 1. L - Isoleucine ..590 mg 2. L - Leucine 770 mg 3. L - Lysine acetate ..870 mg (free base.. 620 mg) 4. L - Methionine ..450 mg 5. L - Threonine .340 mg 6. L - Tryptophan .. 130 mg 7. L - Valine . 560 mg 8. L - Phenylalanine .. 480 mg

Nonessential Amino Acids

1. 2. 3. 4. 5. 6.

L - Alanine .. 600 mg L - Arginine 810 mg L - Histidine 240 mg L - Proline 950 mg L - Serine . 500 mg Aminoacetic acid .. 1.19 g

Enteral Nutrition
Enteral nutrition products may be administered orally, via nasogastric tube, via feeding gastronomy, or via needle-catheter jejunostomy. These products are formulated to contain vitamins, minerals, carbohydrates, proteins, fats and caloric requirements to meet specific needs of the patient. The formula diets may be monomeric or oligomeric ( amino acids or peptides and simple carbohydrates) or polymeric ( more complex protein and carbohydrates sources. Example: Protein - ProMod Powder, Propac Powder Carbohydrates - Moducal Powder Fat - Lipomul Liquid Fewer calories - Ensure HN, Sustacal, and Osmolite HN

Intravenous Infusion Devices

Advances

in infusion technology and computer technology have resulted in devices with extremely sophisticated drug-delivery capabilities

Example: Multiple-rate programming, pump or controller operation)

Special Considerations Associated with Parenteral Therapy

Adsorption Of Drugs Some drugs are adsorbed onto the inner lining of IV containers and tubing or administration sets. Examples of drugs that have implicated with this phenomenon: 1. Chorpromazine HCl 6. Diazepam 2. Insulin 7. Promazine HCl 3. Promethazine HCl 8. Thiopental sodium 4. Trifluoperazine HCl 9. Warfarin sodium 5. Thioridazine HCl

Another Example: Nitroglycerin - should always be prepared in glass containers, and is adsorbed (40 to 80% of total dose) to polyvinylchloride (PVC), a plastic commonly used in administration components and some infusion containers, therefore, it should be packaged with special non-PVC tubing to avoid loss <5% of the drug into the tubing during administration.

Selected Infusion Devices Used in Parenteral Nutrition Support

1. Volumetric Infusion Pumps AVI 2000 #200: Flo-Gard 8100; IMED 2. Multiple-rate Programmable Pumps CADD-TPN 3. Volumetric Infusion Pumps - Provider one; Quest 521 Intelligent 4. Multiple-solution Programmable Pumps Gemini PC 2; Life Care 5000 Plum;Omni-Flow 4000 5. Others- Breeze Lifecare 175, Coleague 3, Horozon Nxt, Sabratek 600 NOTE: All these devices have their own features like: safety alarm, flow rate error, alarm for air in line, door open, low battery, occlusion, malfunction, invalid rates and others

Handling/Disposal of Chemotherapeuticc Agents for Cancer

In theory, correct and perfect preparation and handling techniques will prevent drug particles or droplets from escaping from their containers while they are being manipulated.

Basic Steps in handling Chemotherapeutic Agents

1. Utilizing vertical laminar flow hoods (or bacteriological gloves boxes) for the preparation and reconstitution of cytotoxic drugs. 2. Wearing protective gloves and mask during product preparation 3. Handling and disposing of cytotoxic drugs centrally utilizing specially designed waste containers and incineration. 4. Periodic monitoring of personnel involved with handling admixtures of cytotoxic drugs (CBC, blood chemistry screen, differential cell count) 5. Informing personnel handling cytotoxic drugs that a potential risk to their health exists. 6. Instituting specialized labeling of containers to ensure proper handling and disposal of the cytotoxic agent.

Other Injectable Products

Pellets or Implants are sterile, small, usually cylindricalshaped solid objects about 3.2 mm in diameter and 8 mm in length, prepared by compression and intended to be implanted subcutaneously for the purpose of providing the continuous release of medication over prolonged period of time

The pellets - implanted under the skin (thigh or abdomen) with special injector or by surgical incision - used for potent hormones. The implanted pellets, which might contain 100 times the amount of drug. Example: (desoxycorticosterone, estradiol, testosterone) given other routes are release slowly into general circulation Pellets were formulated with no binders, diluents, or excipients, to permit total dissolution and absorption of the pellets. Example: Levonorgestrel

 Levonorgestrel Implants These are a set of six flexible, closed capsules of a dimethylsiloxane/methylvinylsiloxane copolymer, each containing 36 mg of the progestin levonorgestrel These are found in an insertion fit to facilitate surgical subdermal implantation through a 2 mm incision in the mid-portion of the upper arm about 8 to 10 cm above the elbow crease. These are implanted in a fan like pattern, about 150 apart, for a total of 750. Removal after the end of the 5th year. The dose of levonergestrel is about 85 mcg/day by 9 months, and to about 35 mcg/day by 18 months, with a further decline thereafter to about 30 mcg/day.

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.

 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

Peritoneal Dialysis Solutions allowed to flow into the peritoneal cavity, are used to remove toxic substances normally excreted by the kidney The solutions are made to be hypertonic (with dextrose) to plasma to avoid absorption of water from the dialysis solution into the circulation Hemodialysis Is employed to remove toxins from the blood. In this method, the arterial blood is shunted through a polyethylene catheter through an artificial dialyzing membrane bathed in an electrolyte solution. Following the dialysis, the blood is returned to the body circulation through a vein.

 Examples of Irrigation Solutions 1. Acetic acid Irrigation, USP - This solution is employed topically to the bladder as a 0.25% solution for irrigation. It is administered to wash blood and surgical debris away while maintaining suitable conditions for the tissue. 2. Neomycin and Polymixin B Sulfate Solution for Irrigation, USP - Employed as a topical antibacterial in the continuous irrigation of the bladder.

Examples

of Irrigation Solutions

3. Ringers Irrigation, USP - It is used topically as an

irrigation and must be labeled not for injection. The solution is sterile and pyrogen free.

4. Sodium Chloride Irrigation, USP - This solution is employed topically to wash wounds and into body cavities where absorption into the blood is not likely. The solution also employed rectally as an enema for simple evacuation and also for colonic flush. 5. Sterile Water for Irrigation, USP - The label designations for irrigation only and not for injection must appear prominently on the label. The water must not contain any antimicrobial or other added agent.