1. Sterile Dosage Forms 434 PHT King Saud University
Nahla S. Barakat, Ph.D
King Saud University
College of Pharmacy Dept. of Pharmaceutics
4/15/2017
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2. The course topics
Introduction and characteristics of sterile dosage forms.
Methods of sterilization
Composition of Sterile Dosage Forms.
Large Scale preparation of Sterile Products.
Handling and Administration.
Large Volume Sterile Solutions.
IV Admixtures and incompatibilities.
Ophthalmic preparations.
Reference:
Sterile dosage forms, preparation, clinical application. Salvatore Turco. 1996
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3. Sterile products:
Sterile dosage form refers to a product of a general group of pharmaceuticals having in common the characteristic of sterility, i.e., freedom from living microorganism
The sterile dosage forms in general use:
- Injections Infusion fluids
- Radiopharmaceuticals Sterile solids
- Sterile suspensions
-Ophthalmic solutions, suspensions, and ointments
-Solution for irrigation
- Diagnostic agents
- Peritoneal dialysis solutions
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4. Parenteral products are dosage forms intended for
administration by injection, infusion or implantation.
Major routes of Parenteral administration:
Intradermal Subcutaneous
Intramuscular Intravenous
Intra-arterial Intraspinal
Intra-articular Intracardiac
Hypodermoclysis
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5. Subcutaneous (21) Intravenous (21) Intradermal (23) Intramuscular (20)
Intra arterial (20-22)
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6. Official Types of Injections: 1. Solutions of Medicinal
Example: Codeine Phosphate Injection
Insulin Injection
2. Dry solids or liquid concentrate does not contain diluents etc.
Example: Sterile Ampicillin Sodium
3. If diluents present, referred to as.....for injection
Example: Methicillin Sodium for injection
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7. 4. Suspensions "Sterile....Suspension" Example: Sterile Dexamethasone Acetate Suspension 5.Dry solids, which upon the addition of suitable vehicles yield preparations containing in all respects to the requirements for sterile suspensions. Title: Sterile....for Suspension Example: Sterile Ampicillin for Suspension 6. Injectable Emulsions: Example: Propofol injection
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8. Formulation of Parenteral: Therapeutic agents Vehicles Water
Water miscible vehicles
Non- aqueous vehicles
Added substances (Additives)
Antimicrobials
Antioxidants
Buffers
Bulking agents
Chelating agents
Protectants
Solubilizing agents
Surfactants ix. Tonicity- adjusting agents
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9. Commonly Used IV Abbreviations Fluids
IV Component
Abbreviation
2.5% dextrose in water
D2.5W
5% dextrose in water
D5W
5% dextrose and lactated Ringer’s solution
D5RL or D5LR
10% dextrose in water
D10W
5% dextrose and normal saline
D5NS
2.5% dextrose and 0.45% normal saline
D2.5½ NS
5% dextrose and 0.45% normal saline
D5 ½ NS
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10. Commonly Used IV Abbreviations: Fluids
IV Component
Abbreviation
Normal saline NS
0.45% normal saline
0.45%NS or ½ NS
lactated Ringer’s solution
RL or LR
sterile water for injection
SWFI
bacteriostatic water for injection
BWFI
sterile water for irrigation
SW for irrigation
normal saline for irrigation
NS for irrigation
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11. Commonly Used IV Abbreviations: Electrolytes
IV Component
Abbreviation
potassium chloride
KCl
potassium phosphate
K phos or KPO4
potassium acetate
K acet
sodium phosphate
Na phos or NaPO4
sodium chloride
NaCl
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12. Commonly Used IV Abbreviations: Additives
IV Component
Abbreviation
multivitamin for injection
MVI
trace elements TE
zinc (a trace element) Zn
selenium (a trace element) Se
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13. Liquid drugs are supplied in prefilled syringe, heat-sealed ampoules, vials sealed with rubber closure.
Ampoules are intended for single dose only, do not provide dose flexibility.
A 5 micron filter needle should be used when drawing the contents of an ampoule into a syringe since glass particles may have fallen inside the ampoule when the top was snapped off.
It is useful to wrap an alcohol wipe or small piece of gauze around the top of the ampoule before breaking it.
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14. 2 1 3
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15. The product is easier to remove from vials than form ampoules.
Vials may be designed for single-dose or multi-dose use (contain preservative). Glass or plastic container
Advantages:
The product is easier to remove from vials than form ampoules.
The vials can hold multiple doses.
Eliminate the risk of glass particles contamination during opening.
Some drugs are not stable in liquid form and so are put into the powder form and reconstituted before use.
Disadvantages:
The rubber stopper can become cored
causing a small bit of rubber to enter the solution.
Possible error in dose calculation
Increased waste
Increased microbial contamination
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16. 1 2
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17. Double chambered vials
Mix-O-Vial (Upjohn)
Can be used to package a sterile powder with its vehicle.
The top chamber contain sterile water for injection, is separated from the bottom chamber holding the sterile powder by a rubber plug located at the constriction of the container.
External pressure is applied to the outer rubber closure to dislodge the inner closure and mix the contents of the components. Ex.: Solu-Cortef, kefzol.
A convenient way to separate unstable drug from the diluent
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18. Prefilled disposable cartridge or syringes:
Are designed for maximum convenience. The injection is filled into a glass cartridge with needle attached and administered with a reusable stainless steel or plastic holder.
The other type of prefilled syringe consists of a glass tube closed at both ends with rubber stoppers. The prefilled tube is placed into a specially designed syringe that has needle attached to it.
After using this type of prefilled syringe, all of the pieces are discarded.
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19. Ease of administration, reduction of medication error,
Advantages:
Ease of administration,
reduction of medication error,
increase assurance of sterility,
good control of drugs (narcotics),
adequate labeling save nurses' time.
Emergency drugs as:
Sodium bicarbonate, epinephrine,
Ca chloride, lidocaine, atropine are available for
use as IV in this type of prefilled syringe.
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20. Syringe tips: i- Luer-Lok Tip ii- Luer-Slip Tip iii- Eccentric Tip
iv- Catheter Tip iv
iii
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21. 4/15/2017
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22. Intravenous Access Devices
Syringes: are devices for injection, withdrawing fluids. Syringes consist of glass or plastic barrel with a tight-fitting plunger and tip provides the point of attachment for a needle.
The barrel is graduated in milliliters.
Glass reusable, glass disposable, plastic disposable.
Syringe volume: 1-60 ml
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23. Insulin syringe is graduated in units of insulin (40, 80, 100 unit/ml)
Tuberculin syringes have capacity of 1 ml, a volume of 0.05 ml can be measured with accuracy.
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24. The Needle:
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25. are slanting edges cut into needle tips
Different bevels:
are slanting edges cut into needle tips
Regular bevel: used for IM and SC
Short bevel: used for IV and intraspinal
True short bevel: used for intradermal administration
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26. Various needle lengths are available: range from 1/4 to 6 inches (in).
The choice depends on the site of administration, the depth of penetration into the body.
Compounding parenteral 1 1/4 in
IM in
I.D , SQ /4 - ⅝ in
IV infusion 11/ /2 in
Intracardiac 3 1/2 in
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27. Needle gauge: is the outside diameter of the needle shaft.
Gauge in common range from 13-to 27.
The choice of gauge depends on the viscosity of the fluid to be injected or withdrawn.
Intradermal require G
S.Q require G (insulin)
IM require G
Compounding Parenteral G
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28. 4/15/2017
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29. if the French size is 9, the diameter is 3 mm.
The French catheter scale or "French units" (F) is commonly used to measure the outside diameter of needles, catheters, and other cylindrical medical instruments.
In the French system, the diameter in millimeters of the catheter can be determined by dividing the French size by 3.
D(mm) = F/3 or F = D(mm) * 3
For example,
if the French size is 9, the diameter is 3 mm.
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30. IV Sets
An IV administration set is a sterile, pyrogen-free disposable device used to deliver IV fluids to patients
The set may be sterilized before use by means of radiation or ethylene oxide
The set come in sterile packaging and a sealed plastic wrap
Sets carry expiration dates
Sets carry the following legend:
“Federal law restricts this device to sale by or on the order of a physician.”
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31. PVC sets should not be used for
Each unit is supplied in packaging that ensures the maintenance of sterility
Flanges and other rigid parts of an IV set are molded from tough plastic
Most of the length of the tubing is molded from a polyvinyl chloride (PVC)
PVC sets should not be used for
nitroglycerin, which is absorbed by the tubing
IV fat emulsions, which may leach out of the tubing
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32. the priming of tubing depends on the length of the set
The length of sets varies from 6-inch extensions up to 110- to 120-inch sets used in surgery
the priming of tubing depends on the length of the set
Standard sets have a lumen diameter of 0.28 cm
varying the size of the lumen diameter achieves different flow rates
regulation of flow rates is critical in neonates and infants
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33. 4/15/2017
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34. Intravenous administration set:
Plastic spike to pierce the rubber closure or plastic seal on the IV container
A drip chamber to trap air and permit adjustment of flow rate
cm length polyvinyl chloride tubing terminating in
A gum-rubber injection port ending with rigid needle or catheter adapter
An adjustable clamp (screw or roller type) on the tubing to regulate flow
Air-inlet filters designed as part of the administration set (used with glass container that have no air tubes ).
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35. The most convenient site is often the arm, especially the veins on the back of the hand, or the median cubital vein at the elbow, but any identifiable vein can be used.
Often it is necessary to use a tourniquet which restricts the venous drainage of the limb and makes the vein bulge.
Once the needle is in place, it is common to draw back slightly on the syringe to aspirate blood, thus verifying that the needle is really in a vein. The tourniquet should be removed before injecting to prevent extravasation of the medication.
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37. Different Types of IV Containers
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38. Preparing IV solutions
Preparation should always be done under the supervision of a licensed pharmacist
Medication that is prepared by the technician must be reviewed and approved by the pharmacist
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39. Wear gloves during procedures
Begin any IV preparation by washing your hands thoroughly using a germicidal agent such as chlorhexidine gluconate or povidone-iodine
All jewelry should be removed from the hands and wrists before scrubbing and while making a sterile product
Wear gloves during procedures
Laminar airflow hoods are normally kept running
The exterior surfaces of the hood should be disinfectant weekly with 70% isopropyl alcohol.
Before making the product, thoroughly clean all interior working surfaces using sterile gauze
Prefilters in the laminar -airflow hood will be cleaned monthly.
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40. Working in the laminar flow hood should be free from interruptions
Eating, drinking, talking, or coughing is prohibited in the laminar airflow hood
Working in the laminar flow hood should be free from interruptions
Gather all the necessary materials for the operation and make sure they are:
not expired
free from particulate matter such as dust
check for leaks by squeezing plastic solution containers
Only essential objects and materials necessary for product preparation should be placed in the airflow hood.
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41. Work in the center of the work area within the laminar airflow hood
at least six inches inside the edge of the hood
make sure nothing obstructs the flow of air from the high- efficiency particulate air (HEPA) filter over the preparation area
nothing should pass behind a sterile object and the HEPA filter.
Minimize hand movements within the hood.
Swab all surfaces require puncture with 70% isopropyl alcohol or betadine solution.
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42. syringe should not be larger than twice the volume to be measured
Follow proper procedure for handling sterile devices and medication containers
Remember that the plunger and tip of the syringe are sterile and must not be touched
For greatest accuracy, use the smallest syringe that can hold the desired amount of solution
syringe should not be larger than twice the volume to be measured
Examine all formulations before removing them from the hood
Place all syringes and needles in puncture-proof containers
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43. Peripheral IV injection
This is the most common intravenous access method in both hospitals and pre-hospital services.
A peripheral IV line consists of a short catheter (a few centimeters long) inserted through the skin into a peripheral vein (any vein that is not inside the chest or abdomen). Arms and hand veins are typically used.
The scalp veins are sometimes used in infants
This is usually preferred for drugs that don’t irritate the veins
Patients require short-term IV therapy
Administration of isotonic solutions.
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44. Venflon intravenous cannula
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45. Parts of I.V. cannula
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46. Special consideration: The size of cannula effects four factor;
Needle guage
External diameter of cannula i.e. its catheter
Length of catheter
Flow rate i.e. ml/min
As the gauge number increases the cannula size decreases (14 largest and 24 smallest)
Larger the gauge number is (24G) smaller the cannula/diameter is (0.7mm)
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47. Butterfly catheter — a metal needle with flexible plastic ‘wings’ and a short length of tubing. The ‘wings’ assist in placement and facilitate fixation with tape.
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48. This has several advantages over a peripheral IV:
Central IV lines
Central IV lines flow through a catheter with its tip within a large vein, usually the superior vena cava or inferior vena cava, or within the right atrium of the heart.
This has several advantages over a peripheral IV:
It can deliver fluids and medications that would be overly irritating to peripheral veins because of their concentration or chemical composition. These include some chemotherapy drugs and total parenteral nutrition.
It is used when patients require long-term IV therapy.
Multiple medications can be delivered at once.
Medications reach the heart immediately, and are quickly distributed to the rest of the body.
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49. Central IV lines carry risks of bleeding, infection, gangrene, thromboembolism and gas embolism.
They are often more difficult to insert correctly as the veins are not usually palpable and rely on an experienced clinician knowing the appropriate landmarks and/or using an ultrasound probe to safely locate and enter the vein.
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51. Methods of IV administration
Continuous drip infusion: is the slow primary-line infusion of an IV preparation to maintain a therapeutic drug level or provide fluid and electrolyte replacement. This method achieve continuous, constant blood levels of the drug.
In many instances, drug therapy is accomplished initially by IV push and then maintained slowly and constantly by IV infusion.
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52. Intermittent infusion: allows drug administration at specific intervals (e.g., every 4 h). has a "high" infusion rate, alternating with a low programmable infusion rate to keep the cannula open.
The timings are programmable. This mode is often used to administer antibiotics, or other drugs that can irritate a blood vessel.
Total parenteral nutrition usually requires an infusion curve similar to normal mealtimes.
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53. Not all drugs may be pushed IV
Direct IV push (Bolus): The drug solution is administered in a short time directly into a vein. The injection time is a matter of minutes and varies with different drugs .
Many drugs are given by IV push and are diluted further with the vehicle to reduce the irritability on the vein.
Not all drugs may be pushed IV
Phenytoin and diazepam injections must be given by IV push
They much be pushed at a specified rate that is slow enough to prevent toxicity.
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54. The piggybacked solution is infused into the tubing of the running IV
A piggyback is a small-volume parenteral admixture that is attached to an existing IV line
The piggybacked solution is infused into the tubing of the running IV
usually over a short time, from 30 minutes to 1 hour
Some IV piggybacks are prepared in 250 mL solution because they contain a medication that is irritating to the veins
In some cases, syringes are used instead of piggyback containers to deliver medication into a running IV
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55. Benefits of intermittent infusion:
The method is suitable for patients who don not require administration of large amounts of IV fluids.
It permits greater patient ambulation, as the intermittent infusion injection devices do not require continuous attachment to an IV bottle or bag.
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56. Preparing a Label for an IV Admixture
Labels for IV admixtures should bear the following information:
patient’s name and identification number
room number
fluid and amount
drug name and strength (if appropriate)
infusion period
flow rate (e.g., 100 mL/hr or infuse over 30 min)
expiration date and time
additional information as required by the institution or by state or federal guidelines
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57. There are two basic classes of pumps.
Pumps are electronic devices used to administer parenteral infusions when the use of gravity flow alone might lead to inaccurate dosing or risk patient safety.
Pumps are used to administer parenteral nutrition, chemotherapy, cardiac medications and blood products.
Types of pump
There are two basic classes of pumps.
Large volume pumps can pump nutrient solutions large enough to feed a patient.
Small-volume pumps infuse hormones, such as insulin, or other medicines, such as opiates.
Within these classes, some pumps are designed to be portable, others are designed to be used in a hospital.
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58. They maintain a constant, accurate flow rate
Benefits of pumps:
They maintain a constant, accurate flow rate
They detect infiltration, occlusions and air
Pumps decrease the time of a nurse spends dispensing medications
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59. Types of pumps:
1- Volumetric pump: are used for intermittent infusion of medications such as antibiotics, also used for continuous infusion of IV fluid, Parenteral nutrition
2- Syringe pump: are used to administer intermittent or continuous infusion of medication in concentrated form
3- Mobile infusion pump: is small device designed for ambulatory and home patients, used for chemotherapy, and opiate medications
4- Implantable pump: are infusion device surgically placed under the skin to provide a continuous release of medication, typically an opiate, this type has a lower index of infection
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60. 5-patient-controlled analgesia (PCA), in which repeated small doses of opioid analgesics are delivered on demand, with the device coded to stop administration before a dose that may cause hazardous respiratory depression is reached.
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