Chapter-11
Syllabus: Parenteral dosage forms-Definition, General requirements for parenteral dosage forms. Types of parenteral formulations, vehicles, adjuvant, processing and personnel, Facilities and quality control.Preparation of Intravenous fluids and admixtures-Total parenteral nutrition, Dialysis fluids. Sterility testing: particulate matter monitoring- Faculty seal packaging.
= Parental Preparations =
• Parenteral preparations are those pharmaceutical products that are given by other than oral routes.
• Transfusion fluids and injections are parenteral preparations. Injections are the sterile solutions or suspension of drugs in aqueous or oily vehicle meant for introduction into the body by means of an injectable needle under or through one or more layers of the skin or mucous membrane.
• Injections should be sterile, isotonic and free from foreign particles, such as dust, fibres etc.
• They should be introduced through the same route for which they are intended. For example, an oily suspension meant for intramuscular injection may be very dangerous if it is administered by intravenous injection.
• Similarly, those potent drugs which are required to be given through intramuscular injection may prove very fatal if it is given by intravenous route.
Advantages of Parental Products =
(1) Onset of action is quick.
(2) The drugs which cannot be administered by oral route, can be administered by this route.
(3) The patients who are vomiting or unconscious can not take drug by oral route. In such cases the drug can be administered by this route.
(4) The drug action can be prolonged by modifying the formulation.
(5) Transfusion fluids containing nutritives like glucose and electrolytes such as sodium chloride can be given by this route.
Disadvantages of Parental Products=
(1) Injection causes pain at the site of injection.
(2) The trained persons are required to administer the drugs.
(3) The administration of a drug through wrong route of injection may prove to be fatal.
(4) It is difficult to save a patient when over dose is given.
(5) There are chances of sensitivity reaction or allergic reaction of a drug by an individual. These reactions are sometimes very fatal and lead to death.
Routes of Administration of Parental Products =
The various routes of administration of parenteral preparations are as follows:
1. Intradermal (intracutaneous) injections : These are given in between dermis and epidermis. Skin of the left forearm is usually selected for giving the injection. Generally, 0.1 to 0.2 ml of parenteral solution is injected by this route. The route is used for diagnostic purposes and for testing the sensitivity of the injectables.
2. Hypodermis (subcutaneous) injections : These are made under the skin, into the subcutaneous tissue. The volume of 1.0 ml or less, is usually injected into the upper arm. This is the most popular route, because it is convenient for the patient and the doctor.
3. Intramuscular injections : These injections are given into the muscular tissues. The muscles of the shoulder, thigh or buttock are usually selected. Generally, volume upto 2.0 ml is administered by this route and should not exceed 4.0 ml at one site. Aqueous or oily suspensions and oily solutions can be administered by this route.
4. Intravenous injections : These injections are made into a vein and therefore introduced directly into the blood stream. The median basilic vein near the anterior surface of the elbow is usually selected, because it is easily located and connects with the major veins of the arm. Large volume of parenteral solutions ranging from 1 ml to 500 ml or more than that can be injected. The parenteral solution should be isotonic with blood if the volumes of more than 15 ml should be injected. The suspensions and oily injections cannot be injected by this route.
5. Intra-arterial injections : These are similar to intravenous injections and are occasionally used for an immediate effect in a peripheral area. These injections are given directly into the artery.
6. Intracardiac injections : These are given into the heart muscle or ventricle in an emergency only; for example, as a stimulant following cardiac arrest.
7. Intrathecal injections : These are made into subarchnoid space that surrounds the spinal cord. This route is used for giving spinal anaesthesia.
8. Intracisternal injections : These are given in between the first and second cervical vertebrae. This route is used to withdraw C.S.F.(cerebrospinal fluid) for diagnostic purposes and the inner aspects of the vertebra. So it is that portion of vertebral
9. Peridural injections : These are given between the duramater canal not occupied by the duramater and its contents. This route is sometimes used for giving spinal anaesthesia in special cases.
10. Intra-articular injections : These injections are given into the liquid that lubricate the articulating ends of bones in a joint.
11. Intracerebral injections : These injections are given into cerebrum.
Types of Parenteral Preparations
Parenteral preparations can be classified as follows:-
1. Solutions or emulsions of medicaments suitable for injections : These are commonly called as injections. The parenteral preparation in this form may be supplied in single dose containers or multiple dose Its volume varies from 0.5 ml to a litre e.g., atropine containers, sulphate injection, dextrose injection.
2. Sterile solids : Drugs which are not stable in solution are suitable solvent immediately before its administration e.g., benzyl peni prepared and supplied as dry sterile solids which are dissolved in cillin G sodium injection.
3. Sterile suspensions : These are the sterile suspension of drugs in a suitable solvent which are administered by intramuscular route e.g., sterile hydrocortisone acetate suspension, and sterile chloramphenicol suspension.
4. Transfusion fluids : These are the parenteral solutions which They are generally used for are administered by intravenous route.nutrition and to maintain the electrolyte balance e.g., ringer solution, dextrose injection, sodium chloride injection.
General Requirements for Parental Dosage Forms=
The formulation of parenteral products involve careful consideration of the following requirements:-
1. Stability : The stability of parenteral preparation is very important. The physical as well as chemical stability of parenteral preparation must be maintained during storage.
2. Sterility : The parenteral preparations should be free from all types of microorganisms. An aseptic conditions are required to be maintained during the preparation of parenteral products and its administration. The parenteral product must pass the test for sterility.
3. Free from pyrogens : The parenteral preparations should be free from toxin and pyrogens. It is necessary that the parenteral products must pass the test for pyrogen, because contaminated parenteral product causes rise in body temperature after its administration.
4. Free from foreign particles : The parenteral products should be free from foreign particles such as dust and fibres. To ensure this, the parenteral products must pass the clarity test.
5. Isotonicity : The parenteral preparations should be isotonic with blood plasma and body fluids. It is very important, in order to avoid any complications on the administration of parenteral products.
6. Specific gravity : The parenteral products meant for intra-spinal injections should have the same specific gravity as that of spinal fluid into which the same are to be injected.
7. Chemical purity : The parenteral products should be free from chemical impurities or it should be within certain limit as specified in the monograph of that preparation in the pharmacopoeia.
Formulation of Parenteral Preparations =
The formulation of parenteral preparations need careful planning, thorough knowledge of the medicaments and adjuvants to be used. The excess use of adjuvants in parenteral products should be avoided as some of these may interfere with the drug. In the preparation of parenteral products, the following substances are added to make a stable preparation:-
(1) Vehicles
(2) Adjuvants
(a) Solubilising agents
(b) Stabilizers
(c) Buffering agents
(d) Antibacterial agents
(e) Chelating agents
(f) Suspending, emulsifying and wetting agents
(g) Tonicity factors
1. Vehicles : There are two types of vehicles which are commonly used for the preparation of injections:-
(a) Aqueous vehicles : Water is used as vehicle for majority of injections because water is tolerated well by the body and is safest to administer. The aqueous vehicle used are:-
(i) Water for injection.
(ii) Water for injection free from CO2.
(iii) Water for injection free from dissolved air.
Water for injection is a sterile water, which is free from volatile, non-volatile impurities and also from Pyrogens are by-product of bacterial metabolism. Pyrogens are polysaccharide, thermostable, soluble in water, unaffected by bactericide Pyrogens.and can pass through bacteria proof filters.Pyrogens can be removed from water by simple distillation process using an efficient trap which prevents the pyrogen to enter into the condenser. Immediately after the preparation of water for injection, it is a filled into the final container, sealed and sterilised by autoclaving. Water for injection, contaminated with pyrogens may cause rise in body temperature if injected. Hence, test for pyrogen is done to ensure that water for injection is free from pyrogens.
(b) Non-aqueous vehicles : The commonly used non-aqueous vehicles are oils and alcohols. Fixed oils, such as, arachis oil, cottonseed oil, almond oil and sesame oil are used as vehicle. The oily vehicles are generally used when depot effect of drug is required or the medicaments are insoluble or slightly soluble water or the drug is soluble in oil e.g., dimercaprol injection by using arachis oil as vehicle. Ethyl alcohol is used in the preparation of hydrocortisone injection, Hydrocortisone is insoluble in water, hence the solution is made in 50% alcohol. Alcohol causes pain and tissue damage at the site of injection. Therefore it is not used commonly.Propylene glycol is used as a vehicle in the preparation of digoxin injection. It is relatively non-toxic but it causes pain on s/c or ilm injection. Sometimes polyethylene glycol and glycerin usually diluted with sterile water are used to prepare solutions for injections. They are used as solvent as well as to increase the stability of certain preparations.
2. Adjuvants : These substances are added to increase the stability or quality of the product. These adjuvants should be used only when it is absolutely necessary to use them. While selecting the additives, care must be taken that they should be compatible both physically and minimum possible quantity. The following adjuvants are commonly chemically with the entire formulation. They should be added in used in preparing the stable parenteral preparations:-
(a) Solubilising agents : These are used to increase the solubility of drugs which are slightly soluble in water. The solubility of drug is increased by using surface active agent like tweens and polysorbates or by using co-solvents.
(b) Stabilizers : The drugs in the form of solutions are more liable to deteriorate due to oxidation and hydrolysis. The stabilizers are added in the formulation to prevent this. The oxidation can be prevented by adding a suitable antioxidant, such as, thiourea, ascorbic acid, sodium metabisulphite, or the product is sealed in an atmosphere of nitrogen or carbon dioxide. Hydrolysis can be prevented by using a non-aqueous vehicle or by adjusting the pH of the preparation.
(c) Buffering agents : The degradation of the preparation which is due to change in pH, can be prevented by adding a suitable buffer to maintain the desired pH. For example, citric acid and sodium citrate, acetic acid and sodium acetate.
(d) Antibacterial agents : These substances are added in adequate quantity to prevent the growth of microorganism during storage. So these substances acts as preservatives. Antibacterial agents are added in single dose containers, where parenteral products are sterilised by filtration method, and in multi dose containers to prevent microbial contamination.
(e) Chelating agents : Chelating agent such as EDTA (Ethylene diamine tetra acetic acid) and its salts, sodium or potassium salts of citric acid are added in the formulation, to chelate the metallic ions present in the formulation. They form a complex which gets dissolved in the solvent.
(1) Suspending, emulsifying and wetting agents : The suspending agents are used to improve the viscosity and to suspend the particles for a long time. Methyl cellulose, carboxymethyl cellulose, gelatin and acacia are commonly used as suspending agents. Emulsifying agents are used in sterile emulsions. For this purpose lecithin is generally used. The wetting agents are used to reduce the interfacial tension between the solid particles and the liquid, so as to prevent the formation of lumps. They also act as antifoaming agents to subside the foam produced during shaking of the preparation.
(9) Tonicity factors : Parenteral preparation should be isotonic with blood plasma or other body fluids. The isotonicity of the solution may be adjusted by adding sodium chloride, dextrose and boric acid etc. in suitable quantities. These substances should be compatible with other ingredients of the formulation.
Units of concentration : The concentration of ingredients in parental products may be expressed in a number of different ways:
1. Weight per unit volume : e.g., Atropine sulphate injection 600 ug/ml, prednisolone injection 25 mg/ml.
2. Percentage weight / volume : e.g., Dextrose intravenous infusion 5% w/v, and sodium chloride intravenous infusion 0.9% w/v.
3. Millimoles per unit volume : e.g., sodium bicarbonate intrave. nous infusion 150 m.mol each of Na+ and HCO3-/ litre, Potassium chloride solution strong 2 m moles each of K+ and Cl-Iml.
Containers and Closures used for Parenteral Products
The containers used for parenteral products are either made from glass or plastic material. The pharmacopoeia requires the following conditions for a container and closure to be used for parenteral preparations:
1. It should not yield foreign substances to the product.
2. It should be sufficient transparent to allow visual inspection of the content in it.
3. It should not have any adverse effect on the product.
4. It should prevent diffusion in or across the walls.
The following three types of glasses are used for the preparation of containers meant for storage of parenteral preparations.
1. Type I glass : It is also called borosilicate glass or neutral glass. It offers a high hydrolytic resistance due to its chemical composition. It can withstand autoclaving and weathering a
2. Type II glass : It is a soda-lime-silicate glass with high hydrolytic resistance as a result of treatment with moist sulphur dioxide at high temperature. The containers made from this glass are suitable for most acidic and neutral aqueous preparations.
3. Type III glass : It is a soda-lime-silicate glass with only moderate hydrolytic resistance. The containers made from this glass are generally suitable for non-aqueous preparations and powders for reconstitution immediately prior to administration.Containers of type II and type III glass should be used once only.Containers for human blood and blood components must not be reused. Plastics are synthetic polymers such as polyethylene, polyvinyl chloride and polypropylene which are used to make containers for injectables. The standards for plastic containers for parenteral products are given in I.P
Processing of Parenteral Preparations
The following steps are involved in the processing of parenteral preparations:
(1) Cleaning of containers, closures and equipment
(2) Collection of materials
(3) Preparation of parenteral products
(4) Filtration
(5) Filling the preparation in final containers
(6) Sealing the containers
(7) Sterilisation
(8) Evaluation of parenteral preparations
(9) Labelling and packaging.
1. Cleaning of containers, closures and equipment : All the containers, closures and equipment which are required during the preparation of parenteral products are thoroughly cleaned with detergents and washing is done with tap water, followed by clean distilled water and finally rinsed with water for injection. Rubber closures are washed with hot solution of 0.5% sodium pyrophosphate in water. The closures are then removed from the solution, washed with water followed by rinsing with filtered water for injection. On a small scale washing is done manually but on a large scale automatic washing machines are used.
2. Collection of materials : The various ingredients of the formulation of parenteral preparations are weighed and collected in the preparation room. The raw materials required in the preparation of parenteral products should be pure. Water for injection free from pyrogens and microorganisms are used in the preparation of parenteral products.
3. Preparation of parenteral product : The pharmacist should decide the order of mixing and exact method of preparation to be followed before preparing the parenteral products. The parenteral preparations must be prepared under strict aseptic conditions. The ingredients are accurately weighed separately and dissolved in the vehicle as per method of preparation to be followed.
4. Filtration : The parenteral solution so formed is passed through bacteria proof filter, such as, filter candle, seitz filter, membrane filter, and sintered glass filters. The primary objective of filtration is to clarify the solution by removing foreign particles. If the parenteral preparations
are required to be sterilised by means of bacteria proof filters, filtration should be done under strict aseptic condition to avoid contamination of filtered solution, before it is finally transferred into final container and sealed.
5. Filling the preparation in final containers :
• The filtered product is filled into final containers such as, ampoules, vials and transfusion bottles, which are previously cleaned and dried.
• Ampoules filling single doses whereas, vials are used for filling multidoses. Bottles are meant for filling transfusion fluids.
• On small scale, filling is done manually by using hypodermic syringe and needle. On large scale,
• The sterile powders are filled into containers by individual weighing or by using automatic or semi-automatic devices. The filling operation is carried out under strict aseptic precaution.
• During the filling of ampoules, the care should be taken that the solution should be filled below the neck of ampoules and the solution should not touch the neck of the ampoules.
• This will prevent the cracking and staining of the neck of ampoules at the time of sealing.
6. Sealing the containers :
• Sealing should be done immediately after filling. Ampoules are sealed manually on a small scale by rotating the neck of the ampoule in the flames of Bunsen burner. But on a large scale ampoule sealing machine is used in which tip of ampoule is fused to seal it.
• The vials and transfusion bottles are sealed by closing its opening with a rubber closures. The rubber closures are held in place by crimping the aluminium caps which is done manually or by mechanical means.
7. Sterilisation :
• The parenteral preparations should be immediately sterilised after sealing in its final containers. The sterilisation is done by any one of the methods of sterilisation which depends on the nature of medicaments present in parenteral preparations. For thermostable medicament, the parenteral products are sterilised either by autoclaving at a temperature of 115°C to 116°C for 30 minutes or 121°C for 20 minutes or in hot air oven at 160°C for two hours. The thermolabile preparations are sterilised by filtration through a suitable bacteria-proof filters. Parenteral preparations which are sterilised by filtration method may contain a suitable bacteriostatic agent to prevent the growth of microorganisms. When the solutions are used for intravenous or intrathecal injection in doses exceeding 15 ml, the bacteriostatic agent should not be used. The sterilised product is filled into the final containers and sealed. The process of filtration, filling and sealing are done under aseptic conditions.
8. Evaluation of parenteral preparations :
The finished parenteral products are subjected to the following tests, in order to maintain quality control:-
(a) Sterility test
(b) Clarity test
(c) Leakage test
(d) Pyrogen test
(e) Assay
(a) Sterility test : All the parenteral preparations which are supplied in sterile form must confirm to the test for sterility as prescribed in the pharmacopoeia. The test for sterility is done by detecting the presence of viable forms of bacteria, fungi and yeast in parenteral preparations. The sterility test must be carried out under strict aseptic conditions in order to avoid accidental contamination of the product during the test. All glass wares required for the test must be sterile. Culture media required for the growth of aerobic, anaerobic and fungi, are prepared as described in pharmacopoeia. The test for sterility may be carried out either by:-
(a) Membrane filtration method
(b) Direct inoculation method.
The test samples of parenteral preparation are transferred into test tubes containing sterile culture media for aerobic, anaerobic bacteria and fungi. These test tubes are incubated for stated period in the incubator. The presence of turbidity in the culture media indicate the growth of microorganisms and the sample fails to comply with test for sterility. This can be confirmed by repeating the test. The detail of the test for sterility is discussed separately.
(b) Clarity test : Clarity test is performed to ensure that the parenteral products are free from foreign particles. Each parenteral preparation in its final container is subjected individually to a visual inspection to exclude the possibility of foreign particles. The unlabelled containers are held by the neck against strongly illuminated black and white screen. White screen is used for dark coloured particles and black screen for the detection of light coloured particles. The contents of the containers are slowly inverted and rotated. The solution is examined for the presence of foreign particles. If any foreign matter is visible, the same container is rejected. Nowadays, the various instrumental methods such as Coulter counter, has been developed which are widely used in industry.
have been sealed by fusion to ensure that there should not be any
(c) Leakage test : This test is performed only for ampoules which leakage in them. Leakage test is performed in a vacuum chamber. The ampoules are dipped in 1% solution of methylene blue in vacuum chamber and vacuum is applied. When vacuum is released, the coloured solution will enter the ampoules with defective sealing. The presence of dye in the ampoule, confirms the leakage and hence rejected. Vials and bottles are not subjected to this test because of flexibility of rubber.
(d) Pyrogen test : The test is done as per I.P. 2007 to check the presence or absence of pyrogen in all aqueous parenteral preparations. The test involves the measurement of the rise in body temperature of rabbits following intravenous injection of a sterile solution of a parenteral preparation being examined. Rabbits are used to perform this test, preparation because their body temperature increases when pyrogens are introduced into their bodies by parenteral route. (Detail of the test is given separately at the end of this chapter)
(e) Assay : Assay is performed according to the method given in the monograph of that parenteral preparation in the pharmacopoeia. Assay is done to check the quantity of medicament present in the parenteral preparation.
9. Labelling and packaging : After evaluation of the parenteral preparation, the ampoules, vials and transfusion bottles are properly labelled and packed. The label should state:-
(1) Name of the preparation
(2) Quantity of the preparation
(3) Mfg. Lic. No.
(4) Batch No.
(5) Date of manufacture
(6) Date of expiry
(7) Storage conditions
(8) Retail price
(9) Manufacturer's address.
Production Facilities
The manufacture of parenteral preparation requires special precautions and facilities in order to maintain sterility and freedom from particulate matter. The production area where sterile parenteral preparations are manufactured can be divided into five sections:
(1) Clean-up area
(2) Preparation area
(3) Aseptic area
(4) Quarantine area
(5) Finishing and packaging area
1. Clean-up area :
It is not an aseptic area. All the parenteral products must be free from foreign particles and microorganisms. The area and atmosphere of the room where manufacturing of parenteral products are done must be free from dust, fibres and microorganisms. Clean up area should be constructed to withstand moisture, steam and detergent. Ceiling and walls can be coated with materials which should should be fitted to remove heat and humidity for the comforts of persons prevent the accumulation of dust and microorganisms. Exhaust fans working in this area. This area should be kept clean so that contaminants may not be carried into aseptic area. The containers and closures are properly washed and dried in this area.
2. Preparation area :
In preparation area, the ingredients of the parenteral products are mixed and preparation is made for filling operation. Although it is not essential that, this area should be aseptic, but strict precautions are required to prevent any contamination from outside. Cabinets and counters should be made of stainless steel and they are filled in such a way that no space is left for the dirt to accumulate. Ceiling, walls and floor should be sealed and suitably painted to keep them thoroughly clean.
3. Aseptic area :
From preparation area the parenteral formulation will be transferred to aseptic filling area. The parenteral preparations are filtered, filled into the final containers and subsequently sealed. The entry of personnel into aseptic area should be through an air lock. To maintain sterility, specially trained persons should be selected to work. They must be orderly, neat and reliable. They are required to wear sterile clothes and should be subjected to physical examination at regular intervals to ensure that they are not carrier of any infectious disease. There should be minimum movement in the aseptic area.
Ceiling, walls and floor of aseptic area should be sealed and painted, so that they can be washed or treated with aseptic solution or sprayed Stainless steel counters should be fitted on the walls.
Mechanical equipment should be housed in stainless steel cabinet in order to prevent dirt to accumulate on it.
Mechanical parts that will come in contact with the parenteral product should be separated so that they can be sterilised.
The air in the aseptic area should be free from fibres, dust and microorganism. This can be achieved by the use of high efficiency particulate air filters (HEPA) which can remove particles upto 0.3micro meter. HEPA filters are fitted in laminar air flow system, in which air free from dust and microorganism flows with uniform velocity. The air is supplied under positive pressure which prevents particulate contamination from sweeping from adjoining areas. Ultra violent lamps are fitted order to maintain sterility.
4. Quarantine area :
A batch of parenteral products after its filling, sealing and sterilisation are held up in this area. The random samples of parenteral product of different batches are in the analytical laboratory for its evaluation. Those parenteral products which passes all the quality control tests are transferred into finishing or packaging area.
5. Finishing and packaging area :
The parenteral products are properly labelled and packed. Proper packaging is essential to provide protection against physical damage from transportation, handling and storage. The labelled containers should be packed in cardboard or plastic containers. Ampoules should be packed in partitioned boxes. The packed parenteral products are temporarily stored till it is finally disposed off.
Preparation of Intravenous Fluids=
Large volume of parenteral solutions intended to be administered by intravenous route are commonly called intravenous fluids. The intravenous fluids are administered to supply body fluids, elecolytes or provide nutrition to the body. Intravenous fluids are available in packs of 100ml to 1000ml.
All precautions must be observed during the preparation of intravenous fluids so that they are free from foreign particles and microorganism. They should be isotonic with body fluids. Since large volume of intravenous fluids are administered at a time, no bacteriostatic agent should be included in the formulation of intravenous fluids. The intravenous fluids should be free from pyrogens as large volume of these fluids may cause serious thermal reactions in the patient. The following are some of the commonly used intravenous fluids:-
Dextrose injection I.P. These are available in the concentration of
5, 10, 25 and 50% w/v solution. This solution is used as fluid and nutrient replenisher.
Sodium chloride and dextrose injection I.P. It contains sodium chloride from 0.11 to 0.9% and dextrose from 2.5 to 25%. The solution is used as fluid, nutrient and electrolyte replenisher.
Sodium chloride injection I.P. It contains 0.9% sodium chloride. It is also known as normal saline solution. The solution is used as isotonic vehicle, as fluid and electrolyte replenisher.
Sodium lactate injection I.P. It contains 1.75 to 1.95% w/v of sodium lactate. It is used as fluid and electrolyte replenisher.
Mannitol injection It contains 5, 10, 15 and 20% mannitol and is used as diagnostic aid and renal function determination and diuretic.
Mannitol and sodium chloride injection It contains 5, 10, 15%mannitol and 0.45% sodium chloride. It is used as diuretic.
Ringer injection I.P. It contains 0.86% sodium chloride, 0.03% potassium chloride, and 0.33% calcium chloride. The solution is used as fluid and electrolyte replenisher.
Ringer lactate solution for injection I.P. It contains 2-7 mEq calcium, 4 mEq potassium, 130 mEq sodium and 2.45 g lactate per litre. The solution is used as systemic, alkaliser fluid and electrolytic replenisher.
The intravenous fluids are commonly used for a number of clinical conditions:
(1) Maintenance therapy for those patients who have undergone surgery, or to undergo surgery, or unconscious and are unable to take fluids, electrolytes and nutrition orally.
(2) In replacement therapy, in those patients who have suffered a heavy loss of fluid and electrolyte due to severe diarrhoea, vomiting and burns.
(3) Means of providing basic nutrition.
(4) For providing total parenteral nutrition (TPN).
(5) As vehicle for other drug substances.
Preparation of Intravenous Admixtures
When one or more sterile products are added to an intravenous fluid for administration, the resulting combination is known as intravenous admixture. These intravenous admixtures are generally prepared extemporaneously by nurses, by mixing drugs to the transfusion fluids. The drugs are incorporated into a bottle of large volume transfusion fluids by injected it through a rubber closure. This practice is very dangerous and it may lead to:-
1. Microbial contamination : The intravenous fluids contains no bactericide but contains sugar and amino acid, which are richest source of multiplication of bacteria. So there are more chances of bacterial contamination if the mixing is not done under aseptic condition.
2. Incompatibility : Physical, chemical and therapeutic incompatibilities may occur due to interaction between additives and intravenous fluids. Physical incompatibility will show change in colour, crystal or precipitate formation etc. Chemical incompatibility results from hydrolysis, oxidation, reduction or complexation and can be detected only with a suitable analytic method. The therapeutic incompatibility result in undesirable antagonistic or synergesic pharmacological activity. For example, penicillin or cortisone antagonises the effect of heparin.
Methods for Safe and Effective Use of Intravenous Admixtures
Following are the few methods for safe and effective use of intravenous admixtures:-
(1) Proper training should be given to nurses and pharmacists for preparation of admixtures.
(2) Nurses should be instructed that they should attach a label bearing date and time of addition of a drug. The quantity of drug mixed should also be given in the label.
(3) The pharmacy department of the hospital, should provide latest informations regarding drug stability and compatibility to the paramedical staff.
(4) The pharmacist should always try to avoid addition of medicaments to transfusion bottles by using some other suitable formulations.
Total Parenteral Nutrition (TPN)
Intravenous administration of calories, nitrogen and other nutrients in sufficient quanity to produce tissue synthesis and anabolism is called parenteral nutrition or parenteral hyperlimentation. The source of nitrogen in TPN fluid is either protein hydrolysates or crystalline amino acids. The crystalline amino acid injections are very costly in comparison to protein hydrolysate injections. Amino acids are the most accessible source of nitrogen and are required for protein formation because the whole proteins are not accepted by the patients. Lipid emulsion of essential fatty acid, such as linoleic acid is generally given at intervals of 2 or 3 days. Water soluble as well as fat soluble vitamins may be added, usually in the form of a multivitamin infusion concentrate. The normal calories requirement for an adult is approximately 2500 per day which can be supplied by injecting dextrose 25%. Generally TPN solution consists of mixtures of amino acid, lipid emulsion, electrolytes and vitamins with trace elements, These solutions are administered slowly through a peripheral vein, where it is diluted by the large volume of blood available, so as to minimise the risk of tissue or cell damage due to hypertonicity of the solution. TPN products are generally administered to avoid multiple injections of nutritional requirements of the patients by the intravenous route. TPN is given to fulfil the nutritional requirements in pre-operative and post- operative conditions.
Dialysis Fluids
Dialysis is a process by which the substances are separated from one another due to their difference in diffusibility through membranes. The fluids used in dialysis are known as dialysis fluids. In cases of renal failure, transplantation of kidney or certain cases of poisoning, dialysis is needed to save the patient. In the case of renal failure, it becomes necessary to remove the waste products and to maintain electrolyte balance. This can be done by haemodialysis or intraperitoneal dialysis.
Haemodialysis
Haemodialysis is done to remove toxins from the blood. In haemodialysis, the blood from an artery is passed through an artificial dialysing membrane, bathed in dialysis fluid. membrane is permeable to urea, electrolytes and dextrose and not to plasma proteins and lipids. So urea which is excess in the blood, pass out in dialysis fluid. After the dialysis, the blood is returned back to the body circulation through a vein. A kidney unit may require more than 1200 litres of solution in a week. So haemodialysis fluid is prepared in concentrated form which can be diluted with deionised water or distilled water before its use.
COMPOSITION OF CONCENTRATED HAEMODIALYSIS FLUID B.P.C.
Dextrose monohydrate
Sodium acetate
Lactic acid
0.4 ml
Sodium chloride
Potassium chloride
Freshly boiled and cooled water to 100 ml
Method : Dissolve dextrose monohydrate, sodium acetate, sodium chloride and potassium chloride in 70 ml of freshly boiled and cooled water. Add Lactic acid. Filter the solution and make up the volume to 100 ml. Pack it in large plastic container. The solution should be stored in a warm place as it is liable to deposit crystals on storage. One litre of concentrate is diluted with 39 litres of wate: for each 40 litres required in the artificial kidney.
Intraperitoneal dialysis In this method, the peritoneal cavity is irrigated with the dialysis solution and the peritoneum acts as the semipermeable membrane thereby the toxic substances normally excreted by kidney are removed. Intraperitoneal dialysis fluid should be sterile and free from pyrogens.
Method : Dissolve the ingredients and mix. Filter the solution, place immediately in suitable containers and sterilise by autoclaving.
STERILITY TEST
After sterilisation, the test for sterility is the most reliable method for determining whether or not the particular lot of material is sterile. Test for sterility is intended for detecting the presence of viable forms of
Particulate Matter Monitoring =
Faulty Seal Packaging=
Pyrogen Testing=
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