C-15 PARENTERALS

PARENTERALS

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

1. Parenteral preparations2. Ophthalmic preparations - for the eye3. Otic preparations - for the ear 4. Nasal preparations - for the nose

& throat5. Irrigating solutions - for washing wounds

or abraded mucous membrane

Parenteral Routes of Parenteral Routes of AdministrationAdministration

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

ROUTESROUTES

PARENTERALSPARENTERALS

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

PARENTERALS ARE PARENTERALS ARE ADMINISTERED BY:ADMINISTERED BY:

PhysicianPhysician’s assistantNurse

PARENTERALS ARE PARENTERALS ARE ADMINISTERED AT:ADMINISTERED AT:

HospitalsClinicsExtended care facilities

Antirheumatic injectables

Brand Name: Enbrel

Generic name:: Etanercept

Manufacture: Immunex

Form::Injectable

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

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

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)


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 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

Hazard Of Intravenous InjectionHazard 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.

Intravenous Route (IV)

INTRASYNOVIAL / INTRASPINAL

INTRATECAL: SPINAL FLUID

INTRAARTERIAL: ARTERIES

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

Advantages:1. Patient Controlled Analgesia (PCA) used to control

pain2. Allows greater degree of ambulation and

independence3. 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 pocketExample: WalkMed PCA

4. Ability to provide constant and uniform analgesia

Intravenous Route (IV)

5. Can prevent pharmacokinetics and pharmacodynamic differences between patients from interfering with the effectiveness of analgesia6. Also permits patients to medicate themselves when there is breakthrough pain.7. Minimizes various side effects8. 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 (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.

Such injuries include:1. Paralysis resulting from neural damage2. Abscesses3. Cysts4. Embolism5. Hematoma6. Sloughing of the skin7. 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


Volume of Administration:limited :

– 5 mL in the gluteal region – 2 mL in the deltoid of the arm.

Injection is 2 to 3 inches deep20 to 22 gauge needle. To avoid staining: it must be injected

only into the muscle mass of the upper outer quadrant of the buttock.


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)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.

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

Subcutaneous Route (SC)Subcutaneous Route (SC)

Intradermal RouteIntradermal 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 AccessSpecialized AccessDevices 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.

Usually, these must be removed within 48 hours after insertion.

The choice of catheter depends on several factors

1. Length of time of the infusion2. Purpose of the infusion3. Condition and availability of the

veinsTypes of Catheter

1. Plain plastic2. Catheter over needle or outside needle3. Catheter inside needle

Specialized AccessSpecialized Access

Official Types of InjectionsOfficial Types of Injections1. 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 InjectionsExample: Cefamandole Sodium for

Injection

3. Drug Injectable Emulsion - Liquid preparations of drug substances

dissolved or dispersed in a suitable emulsion mediumExample: Propofol

Official Types of InjectionsOfficial Types of Injections

4. Drug Injectable Suspension - Liquid preparations of solids suspended in a suitable liquid mediumExample: Methylprednisolone Acetate Suspension

5. Drug Injectable Suspension - Dry solids that, upon the preparations conforming

in all respects to the requirements for Injectable SuspensionsExample: Imipenem;

Cilastatin for Injection Suspension, USP

Official Types of Injections

Official Types of Injections

INSULIN INJECTION, USP PROPOFOL

METHYLPREDNISOLONE METHYLPREDNISOLONE ACETATE SUSPENSIONACETATE SUSPENSION

InjectionsInjections 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

Blood immiscible liquids, such asoleaginous injections and suspensionscan 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

InjectionsInjections

Following differences with other Following differences with other preparationspreparations

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.

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.

Following differences with other Following differences with other preparationspreparations

Solvents and Vehicles for InjectionsSolvents and Vehicles for Injections1. 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.

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 InjectionsSolvents 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. Ringer’s 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

Solvents and Vehicles for InjectionsSolvents and Vehicles for Injections

BACTERIOSTATIC WATER SODIUM CHLORIDE INJECTION, USP; POTASSIUM CHLORIDE

STERILE WATER FOR INJECTION, USP

BACTERIOSTATIC WATER FOR INJECTION, USP

SODIUM CHLORIDE INJECTION, USP

DEXTROSE INJECTION

Characteristics Of Components used Characteristics Of Components used in Compoundingin 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 Nonaqueous Vehicles Selected Vehicles must be: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

Other Considerations Of Selecting Other Considerations Of Selecting Nonaqueous SolventsNonaqueous Solvents

1. Physical and chemical stability2. Its viscosity (syringeability) and its fluidity3. Its boiling point (it should be high to

permit heat sterilization)4. Its miscibility with body fluids5. Its low vapor pressure to avoid problems

during heat sterilization6. Constant purity or ease of purification and

standardization.

Examples of Nonaqueous SolventsExamples 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

Nonaqueous Vehicles…Nonaqueous 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)

SOLVENTS AND VEHICLE FOR INJECTIONSSOLVENTS AND VEHICLE FOR INJECTIONS

Water for Injectionsolventpurified by distillation or by reverse

osmosisstored in tight container with temperature

below or above the range of microbial growth

must be pyrogen free

Added SubstancesAdded 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-irritating3. Must not exert any adverse effect on the product4. Must be compatible in all components of the

formulation5. Must not interfere with:

a. Therapeutic efficacyb. Assay of the active therapeutic compound

Such substances include:Such substances include:

1. Solubilizers

2. Chelating agents

3. Anti-microbial agents

4. Hydrolysis Inhibitors

5. Antioxidants

6. Buffers

7. Tonicity contributors

8. Antifoaming agents

Antifungal/AntibacterialAntifungal/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%

AntioxidantsAntioxidants

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 Classification of Antioxidants Used In Sterile ProductsUsed In Sterile Products

1. Reducing agents - antioxidants which functions by being preferentially oxidizedExamples: 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 consumedExamples: ascorbic acid esters

butyl hydroxytoluene (BHT) tocopherols

3. Synergists - compounds increase the effectiveness of antioxidants, particularly those blocking oxidative reactionsExamples: ascorbic acid citraconic acid

phosphoric acid citric acid tartaric acid

4. Chelating agents - those that complex with catalysts which otherwise would accelerate the oxidative reactionExamples: 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

Classification of Antioxidants Classification of Antioxidants Used In Sterile ProductsUsed In Sterile Products

BuffersBuffers

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 product2. Release of constituents from rubber closures or plastic components in contact with the product3. 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. Acetates2. Citrates3. Phosphates

Tonicity ContributorsCompounds 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

ContainersContainersContainers 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

Based on its chemical resistance, glass compounds are classified into 4 types:

1. Type I - highly resistant borosilicate glass2. Type II - treated soda-lime glass3. Type III - soda lime glass4. NP (nonparenteral) - general purpose soda-lime

glass

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

Containers

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 OilExamples of Some Injections in Oil

Injections Oil Category

Dimercaprol Injection Peanut Antidote to As ,Au, Hg poisoning

Estradiol Cypionate Injection Cottonseed Estrogen Estradiol Valerate Injection Sesame/Castor Estrogen Fluphenazine Decanoate Inj. Sesame Antipsychotic Fluphenazine Enanthate Inj. Sesame Antipsychotic Hydroxyprogesterone Caproate Castor Progestin Progesterone in OilInjection Sesame/Peanut Progestin Testosterone Cypionate Cottonseed Androgen Testosterone Cypionate and Estradiol Cypionate Cottonseed Androgen and

Estrogen Testosterone Enanthate Inj. Sesame Androgen Testosterone Enanthate and Sesame Andragen and

Estrogen Estradiol Valerate

METHODS OF STERILIZATIONMETHODS OF STERILIZATIONSterilization 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 METHODS5 GENERAL METHODS

1. Steam distillation

2. Dry-heat sterilization

3. Sterilization by filtration

4. Gas sterilization

5. Sterilization by ionizing radiation

2 MAIN DIVISIONS OF STERILIZATION2 MAIN DIVISIONS OF STERILIZATION

1. Physical Processes of Sterilization

A. Thermal MethodMicroorganisms 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 heat2. The exposure period3. The moisture present

Steam sterilization is conducted in an autoclave and employs steam under pressureThe 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.

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 Methods1. 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. 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. 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

2 MAIN DIVISIONS OF STERILIZATION

Validation of SterilityValidation 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 forms1. 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 samplesIn moist heat (steam) - Bacillus

stearothermophilusIn dry heat - Bacillus subtilis In ionizing radiation - Bacillus pumilus, stearothermophilus,

subtilis

Pyrogens and Pyrogen TestingPyrogens 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 2 Official Tests for Detecting and Measuring PyrogensPyrogens

1. Bacterial Endotoxins TestUsing 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. Pyrogen TestThe 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 minutesIf 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.

2 Official Tests for Detecting and Measuring 2 Official Tests for Detecting and Measuring PyrogensPyrogens

Depyrogenation Method are as follows: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 PRODUCTION of a sterile preparation of a sterile preparation

consists of the following steps:

1. Compounding

2. Filtration

3. Filling

4. Sealing

5. 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.

SealingSealing will retain the contents of a

sterile product and will assure a tamper-proof presentation.

ContainersContainers

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 form1. Tip-seals: those made by melting sufficient

glass at the tip of the ampul neck to form a bead of glass and close the opening2. 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.

ExamplesExamples of Sterile Drugs prepared and packaged of Sterile Drugs prepared and packaged withoutwithout the presence of phamaceutical additives as the presence of phamaceutical additives as buffers, preservatives, stabilizers, tonicity agents, buffers, preservatives, stabilizers, tonicity agents, and other substancesand other substances

1. Sterile Ampicillin Sodium2. Sterile Ceftazidime Sodium3. Sterile Kanamycin Sulfate4. Sterile Penicillin G Banzathine5. Sterile Tobramycin Sulfate6. Sterile Ceftizoxime Sodium7. Sterile Cefuroxime Sodium8. Sterile Nafcillin Sodium9. Sterile Streptomycin Sulfate

ExamplesExamples of Sterile drugs of Sterile drugs formulated formulated withwith pharmaceutical additives and pharmaceutical additives and intended to be reconstituted prior to Injection intended to be reconstituted prior to Injection

1. Cephradine for Injection2. Dactinomycin for Injection3. Erythromycin Lactobionate for Injection 4. Oxytetracycline Hydrochloride Injection 5. Nafcillin Sodium for Injection6. Hydrocortisone Sodium Succinate for Injection 7. Cyclophosphamide for Injection8. Hyaluronidase for Injection9. Mitomycin for Injection10. Penicillin G Potassium for Injection 11. Vinblastine Sulfate for Injection.

Containers…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.

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.

Containers…Containers…

Packaging, Labeling, and Storage of InjectionsContainers 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 preparation2. 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 administration4. Statement of storage conditions and expiration5. The name of the manufacturer and distributor6. 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 Examples of some Injections Usually Package and Administered in Small VolumePackage and Administered in Small Volume

1. Butorphanol Tartrate Injection - Narcotic Agonist- Antagonist

Analgesic2. Chlorpromazine HCl Injection

- Antipsychotic drug with antiemtic

3. Cimetidine HCl Injection - Histamine H2 antagonist4. Dalteparin Sodium Injection

- Prophylaxis against deep vein thrombosis

5. Dexamethasone Sodium Phosphate Injection - Glucocorticoids

6. Digoxin Injection - Cardiotonic

7. Dihydroergotamine Mesylate Injection - Alpha-adrenergic blocking agent

8. Diphenhydramine HCl Injection - An ethanolamine, non selective

antihistamine9. Furosemide Injection - Loop diuretic10. Granisetron HCl Injection - Prevention of

nausea and vomiting11. Heparin Sodium Injection - Anticoagulant (IV

or SubQ)12. Hydromorphone HCl Injection - Narcotic analgesic


13. Ibutilide Fumarate Injection - An antiarrhythmic drug14. Iron Dextran Injection - Hematinic agent15. Isoproterenol HCl Injection - Adrenergic (bronchodilator)16. Ketorolac Tromethamine Injection - NSAID17. Lidocaine HCl Injection - Cardiac depressant as an

antiarrhythmic18. Magnesium Sulfate Injection - Anticonvulsant/Electrolyte19. Meperidine HCl Injection - Narcotic analgesic20. Metoclopramide Monohydrochloride Injection

- Gastrointestinal stimulant

Examples of some Injections Usually Package Examples of some Injections Usually Package and Administered in Small Volumeand Administered in Small Volume

22. Midazolam HCl - Short acting benzodiazepine CNS depressant

22. Morphine Sulfate injection - Narcotic analgesic23. Naloxone HCl Injection - Narcotic antagonist24. Nalbuphine HCl Injection - Narcotic Agonist-Antagonist

Analgesic25. Oxytocin Injection - Oxytoxic26. Phenytoin Sodium Injection - Anticonvulsant27. Phytonadione Injection - Vitamin K (prothrombogenic)28. Procaine Penicillin G Injection - Anti-infective29. Prochlorperazine Edisylate Injection - Antidopaminergic


Single-dose unit

8 fl oz

2 mLSingle-dose vials

8 mLMulti-dose vials

300 mg/2 mL Product Classification: RX Manufacturer: SMITHKLINE BEECHAM PHARM

HEPARIN SODIUM INJECTION

LANOXIN

BENADRYL

BUTORPHANOL BUTORPHANOL TARTRATE TARTRATE INJECTIONINJECTION

TAGAMET

FUROSEMIDE INJECTION

CIMETIDINE HCL INJECTION>>>>

SODIUM SODIUM BICARBONATE BICARBONATE

INJECTIONINJECTION

>>>IRON DEXTRAN INJECTION

LIDOCAINE<< HCL INJECTION

>>PROCAINE >>PROCAINE PENICILLIN G PENICILLIN G INJECTIONINJECTION

MIDAZOLAM HCL INJECTION>>>>

>>NALBUPHIN HCL

INJECTION

MAGNESIUM SULFATE

PHYTONADIONE

30. Propranolol HCl Injection - Beta adrenergic receptor blocking agent

31. Sodium Bicarbonate Injection - Electrolyte32. Sumatriptan Succinate injection

- treat acute migraine attacks33. Verapamil HCl Injection

- Calcium channel blocking agent


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

INSULININSULIN

2. Human InsulinIt 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 SolutionInsulin 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 B-chain are reversedCompared 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 daysNote: 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 monthsDosage: dosage range subcutaneously is 10 to 80 USP UnitsNPH 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 InjectionA 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 injection2. Humulin 50/50

- combination that consists of 50% isophane insulin suspension and 50% insulin injectionThey contain zinc of 0.01 to 0.04 mg/100 units. Neutral in pH and phosphate bufferedPreservatives: 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 SuspensionThe 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 MixManufactured premix insulin consisting lispro and neutral protamine lispro (NPL) in afixed ratioHumalol 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 injectionIt is estimated that these premixed combinations are used by more than 40% of diabetes patients who inject insulin twice daily

11. Insulin GlargineIt 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 *

Characteristics Onset Peak Duration

Short/Fast-Acting (clear)

5 - 30 mins 1 - 3 hrs 4 - 8 hrs

Intermediate-Acting (milky)

1 - 2 hrs 4 - 12 hrs 16 - 24 hrs

Premixed (Short & Intermediate)

1/2 hr 2 - 12 hrs 16 - 24 hrs

Long-Acting (milky)

4 hrs 8 - 24 hrs 28 - 36 hrs

Insulin Activity Profiles and Compatibility

Insulin Preparations Onset (hr) Peak (hr) Duration (hr) Compatible mixed with

Rapid acting

Insulin Inj (regular) 0.5 to 1 8 to 12 all Lente Prompt Insulin Zinc 1 to 1.5 5 to 10 12 to 16

Suspension(semilente)

Lispro Insulin Sol’n 0.25 0.5 to 1.5 6 to 8 Ultralente, NPH

Intermediate

Isophane Insulin 1 to 1.5 4 to 12 24 regular

Suspension (NPH)

Insulin Zinc Suspension(lente) 1to 2.5 7 to 15 24 regular, semilente

Long acting

PZI (Protamine Zinc Insulin) 4 to 8 14 to 24 36 regular

Extended Insulin Zinc 4 to 8 10 to 30 >36 regular, semilente

Isophane Insulin Suspension

Premixed 50% and Insulin Inj 50%

insulin Isophane Insulin Susp. 0.5 2 to 12 18 to 24 regular, NPH

70% and Insulin Inj, 30%

Examples of Some Injections Administered in Large Volume by IV that may be Administered in Volumes of 1 Liter or More, Alone, or With Other Drugs Added

Injection Usual Content Category/Comments

Amino Acid Injection 3.5,5,5.5,7,8.5,10% crystalline amino Fluid / Nutrient replenisheracids with or without varying concentrations of electrolytes or glycerin

Dextrose Injection,USP 2.5,5,10,20% dextrose, other strengths Fluid/ Nutrient replenisher

Dextrose and sodium Dextrose varying from 2.5 to 10% and Fluid/ Nutrient/ Electrolyte chloride Injection,USP sodium chloride from 0.11 (19 mEq Na) electrolyte to 0.9% (154 mEq sodium)

Mannitol Injection, USP 5,10,15,20 and 25% mannitol Diagnostic aid in renal function determinations; diuretic. Fluid/ Nutrient

Ringers’ Injection, USP 147 mEq sodium, 4 mEq potassium Fluid/ electrolyte calcium, and 156 mEqchloride/ liter

Lactated Ringer’s 2.7 mEqcalcium, 4 mEqpotassium, Systemic alkalinizer; Injection, USP 130 mEqsodium and 28 mEq fluid and electrolyte lactate per liter replenisher

Sodium Chloride 0.9% sodium Chloride Fluid and electrolyte Injection, USP replenisher, isotonic vehicle

INSULIN INJECTION SITES

Large Volume Parenterals Large Volume Parenterals (LVPs)(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 TherapyIs 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 TherapyIs 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 Crohn’s disease, AIDS, burn patients, or those experiencing trauma are candidates for replacement therapy.

Water RequirementThe 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 water1. <10 kg: 100 mL/kg/day2. 10-20kg: 1000 mL plus 50 mL/kg/day for weight over 10 kg3. >20 kg to maximum of 80 kg: 1500 mL

Plus 20 mL/kg/day for weight over 20 kg

Electrolyte Requirement1. 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, surgicaloperations 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 RequirementsBasic 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 hyperalimentationThis 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

Electrolytes1. Sodium…………. 25 mEq2. Potassium …….. 20 mEq 3. Magnesium …… 5 mEq4. Calcium ……….. 5 mEq5. Chloride ……….. 30 mEq6. Acetate ………… 25 mEq7. Phosphate …….. 18 mM

VitaminsVitamins

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 Acids1. L - Isoleucine……… ……..590 mg2. L - Leucine ……………… 770 mg3. L - Lysine acetate ………..870 mg (free base………….. 620 mg)4. L - Methionine …… ……..450 mg5. L - Threonine …………….340 mg6. L - Tryptophan ………….. 130 mg7. L - Valine ………………. 560 mg8. L - Phenylalanine ……….. 480 mg

Nonessential Amino Acids

1. L - Alanine …………….. 600 mg2. L - Arginine …………… 810 mg3. L - Histidine …………… 240 mg4. L - Proline ……………… 950 mg5. L - Serine ………………. 500 mg6. Aminoacetic acid ……….. 1.19 g

Enteral NutritionEnteral 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 PowderCarbohydrates - Moducal PowderFat - Lipomul LiquidFewer calories - Ensure HN, Sustacal, and

Osmolite HN

Intravenous Infusion DevicesAdvances 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 Special Considerations Associated with Parenteral TherapyParenteral Therapy

Adsorption Of DrugsSome 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. Diazepam2. Insulin 7. Promazine HCl3. Promethazine HCl 8. Thiopental sodium4. Trifluoperazine HCl 9. Warfarin sodium5. 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 PumpsAVI 2000 #200: Flo-Gard 8100; IMED

2. Multiple-rate Programmable Pumps – CADD-TPN3. Volumetric Infusion Pumps - Provider one; Quest 521

Intelligent4. Multiple-solution Programmable Pumps

Gemini PC –2; Life Care 5000 Plum;Omni-Flow 40005. Others- Breeze Lifecare 175, Coleague 3, Horozon Nxt, Sabratek 600NOTE: 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 Handling/Disposal of Chemotherapeuticc Agents for CancerChemotherapeuticc Agents for Cancer

In theoryIn theory, , “correct and perfect preparation and “correct and perfect preparation and handling techniques will prevent drug particles handling techniques will prevent drug particles or droplets from escaping from their containers or droplets from escaping from their containers

while they are being manipulated”.while they are being manipulated”.

Basic Steps in handling Chemotherapeutic Agents1. 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 preparation3. 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 ProductsOther Injectable Products

Pellets or Implantsare sterile, small, usually cylindrical-

shaped 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 circulationPellets were formulated with no binders, diluents, or excipients, to permit total dissolution and absorption of the pellets.Example: Levonorgestrel

Levonorgestrel ImplantsThese 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 SolutionsIrrigation solutions are intended to

bathe or wash wounds, surgical incisions, or body tissues.

Dialysis SolutionsMay 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 DialysisSolutions 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 circulationHemodialysis

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 Solutions1. 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.

3. Ringer’s 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.

Examples of Irrigation Solutions

C-15 PARENTERALS

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