Parental Prodcuts Flashcards
1
Q
Parenteral routes of administration
A
- Intravenous (IV): into a vein
- Intramuscular (IM): into a muscle
- Subcutaneous (sub-Q): under the skin
- Intradermal (ID): into the skin
2
Q
What are the two methods of parental administration?
A
Injection
Infusion
3
Q
What are three types of administration devices?
A
Syringes
Needles
Catheter
4
Q
What are the three types of catheters?
A
Rigid-produces more infilitration
Butterfly-for a one time or short term
Flexible-when it needs to be there fro a while
5
Q
The primary use of an i.v. injection is to ______
It is also used for ___ ____ and ___
A
provide a rapid and immediate drug action.
fluid, electrolye, and nutrient supplement
6
Q
Where are two injection sites for IV Drugs?
A
Basilic and Cephalic veins on back of hands
dorsal forearm veins
7
Q
What is the max injection volume for adults
Kids?
A
3L
Less than 3
8
Q
IV administration is subdivided into three categories?
A
- IV Bolus Push
- Intermittent Infusion
- Continuous infusion
9
Q
Intravenous Bolus (IV push)
How much?
Problem?
When is it used?
A
drug is injected into vein via syringe or needle in short time
- 1-2 mls
- Drug is given in short time toxicity could occur
- emergencies
10
Q
Intermittent Infusion
How much?
Problem?
Why is it used?
A
- Drug is diluted at an intermediate volume of fluid 25 to 100 ml infused from 15-60 mins and spaced at 6 hrs
- less consistent drug plasma level than continuous
- Method is safer than IV bolus
11
Q
Continuous infusion
How much?
A
- slowly and continuously administered into a vein
- drug is added to a large volume parenteral fluid (up to 1000 mL)
12
Q
Advantages to Continuous Infusion?
A
fluid and drug therapy to be administered at same time
It provides an excellent control of drug plasma level.
Problems associated with drug toxicity and irritation are minimized.
13
Q
Disadvantages to Continuous Infusion?
A
unstable drugs cannot be administered by this means because of extended run times.
It cannot be used in fluid-restricted patients because of the large volume of administration.
It cannot be used to admix poorly soluble drugs dissolved in water-miscible drugs.
14
Q
Intramuscular route?
A
IM injection is made deep into the layers of muscle
15
Q
What are three areas for IM injection?
Amounts?
A
Butt (up to 5 ml)
Deltoid (up to 2 ml)
Thigh (up to 2 ml)
16
Q
In IM injection
The needles used for the injections are generally ____
A
1/2 inch to 1 1/2 inches long and are 19-23 gauge in size.
17
Q
In IM injection
The point of injection should be as far as possible from major nerves to
A
avoid neural damage.
18
Q
In IM injection
result in
A
lower but more sustained blood concentrations than after IV administration due to an absorption step.
19
Q
Subcutaneous route
A
Admin beneath skin, between dermis and muscle
20
Q
What are injection sites for SubQ
A
1) upper arm
2) anterior surface of the thigh
3) the lower portion of the abdomen
4) the upper back
21
Q
What is the volume for all Sub Q needles?
A
Less than 2 ml
22
Q
In Sub Q
Needles are generally
A
3/8 to 1 inch in length and 24 to 27 gauge in size.
23
Q
In Sub Q
If frequent injections are required
A
the injection sites must be rotated.
24
Q
In Sub Q
The vascularity in the subcutaneous tissue is less than that of muscle tissue, and therefore
A
absorption may be slower than after intramuscular administration.
25
What are most common drugs used in subQ
Heparin and insulin are the most important drugs routinely administered by this route.
26
Intradermal route
ID administration involves injections just beneath the epidermis, within the dermal or skin layer
27
Injection sites for ID
Anterior surface of forearm
28
What is volume limit for Intradermal?
.1 ml
29
In Intradermal injections
| Needles are generally
3/8 inches long and 25 to 28 gauge.
30
In Intradermal injections
| The onset of action and the rate of absorption of medication from this route are
slow
31
In Intradermal injections
| Drugs that are intradermally injected are agents for
diagnostic determinations, desensitization, or immunization.
32
Example of ID injections
tuberculin skin test agent, diphtheria toxin and various allergens
33
What are three things all parental products must have?
- Sterile
- Pyrogen limited
- Free from extraneous insoluble material
34
Sterility
absence of life or the absolute freedom of living organism. No growth of organisms, bacterial, fungal, viral, parasites, etc.
35
Pyrogen (bacterial endotoxin)
bacteria made, produces fever and hypotension when introduced or released into the blood
36
extraneous insoluble materials
any foreign particles, such as glass, fibers, precipitates, and any floating materials.
37
Where can pyrogens come from
microbes that get destroyed during sterilization
38
Sources of particulate may come from
raw materials, processing and filling equipment, the container, and environmental contamination
39
Various forms of parenteral products are available for use
| 4
- Solutions
- Lyophilized Solids
- Emulsions
- Suspensions
40
The form in which manufacturer prepares a given drug for parenteral use depends on the
nature of the drug itself with respect to its physical and chemical characteristics and on certain therapeutic considerations.
41
According to the USP, injectable materials are separated into five general types:
```
Injections
For Injection
Injectable Emulsion
Injectable Suspension
For Injectable Suspension
```
42
Injections:
| whats special?
Liquid preparations that are drug substances or solutions.
| The solution is the fastest acting form and is therefore often used to provide an immediate drug action.
43
For injection:
| Whats special?
-Dry solids that, upon addition of suitable vehicles, yield solutions conforming in all respects to the requirements for injections.
- The solids include drugs that are not stable in liquid media and are prepared by a freeze-drying process.
- The solids are reconstituted with an appropriate vehicle before administration to form solution.
44
Injectable emulsion:
| Whats special?
-Liquid preparations of drug substances dissolved or dispersed in a suitable emulsion medium.
Drugs that are oily or insoluble in an aqueous medium are often formulated as emulsion.
45
Injectable suspension:
| Whats special?
Liquid preparations of solid suspended in a suitable liquid medium
If the drug is insoluble or unstable in water an injection may be prepared as an aqueous suspension
46
excipients
Injectable products contain active drug and inactive ingredients
47
What can be excipients?
1. Vehicles
2. Buffering Agents
3. Preservatives
4. Antioxidants
5. Chelating Agents
6. Tonicity Agents
48
Vehicles
is the medium in which formulation is prepared
49
most commonly used vehicle for parenteral preparations
water
50
Water for Injection, USP
is pyrogens-free, purified water and contains no more than 1 mg/100 mL of trace elements.
51
How is water for injection prepared?
What should be noted with regards to sterility?
- It is prepared by distillation or reverse osmosis and is intended to be used within 24 h.
- It is not required to be sterile when used in the manufacture of injectable products. However, the final products requires the terminal sterilization.
52
Sterile water for Injection, USP
is water for injection that has been sterilized.
53
Sterile water for Injection, USP
| It may contain slightly more than 1mg/100 mL of solids because of the leaching of solids from
the glass container during sterilization.
54
Sterile water for Injection, USP
| It is stored in single-dose containers
no larger than 1L
55
Sterile water for Injection, USP is commonly used as a vehicle for?
dry-powder injectable products.
56
Bacteriostatic water for Injection, USP
is sterile water for injection that contains one or more antimicrobial agents (e.g. 0.9% benzyl alcohol).
57
Bacteriostatic water for Injection, USP
| The container label must state the
names and proportions preservatives.
58
Bacteriostatic water for Injection, USP
| is packed in prefilled syringes or in vial containing not more than
30 mls.
59
Bacteriostatic water for Injection, USP
| Its use in large volume injectable is limited because of
potential toxicity associated with preservatives.
60
Bacteriostatic water for Injection, USP
| USP labeling requirements demand that the label state
Note for use in Neonates
61
Sodium chloride injection, USP
is sterile isotonic solution of sodium chloride (0.9 %) in water for injection, which contains no antimicrobial agents.
62
Sodium chloride injection, USP
| It is often used as a vehicle in preparing
parenteral solutions and suspensions.
63
Sodium chloride injection, USP
| is also used as a catheter or IV line flush
to maintain patency.
64
Bacteriostatic Sodium chloride injection, USP
is sterile isotonic solution of sodium chloride (0.9 %) in water for injection, which contains antimicrobial agents
65
Bacteriostatic Sodium chloride injection, USP
| is packed in containers containing not larger
30 mL.
66
Bacteriostatic Sodium chloride injection, USP is
| often used as a vehicle in preparing __________ and as a a _________ or ____________
parenteral solutions
catheter or
IV line flush
67
5% Dextrose Injection, USP (D5W)
is isotonic with blood and uses as a water source and vehicle.
68
Ringer’s Injection, USP
is a sterile solution of sodium chloride, potassium chloride, and calcium chloride in water. Ringer’s is employed as a vehicle for other drugs or alone as an electrolyte replenisher and plasma volume expander
69
Some parenteral fluids are __________ (less than 240 mOsm/L) or h__________ ( greater than 340 mOsm/L).
hypotonic
| hypertonic
70
Hypotonic solutions can be used
to dilute excess serum electrolytes as in hyperglycemia (high blood sugar).
71
Patients receiving hypotonic solutions should be monitored closely, as these solutions may cause
hemolysis
72
Hypertonic solutions can be used
to correct electrolytes imbalance, as in loses from excess vomiting and diarrhea.
73
Patients receiving hypertonic solutions should be monitored to prevent ____________, especially if the solutions are extremely concentrated or are being given at rapid speed.
body fluid overload
74
Two main reasons for use of a Non-aqueous vehicle are:
1. Limited water solubility of the drug
| 2. Susceptibility to hydrolysis
75
Water immiscible vehicles
1. Fixed oils
2. Ethyl oleate
3. Isopropyl Myristate
4. Benzyl benzoate
76
Water miscible vehicles (cosolvents)
1. Propylene glycol
2. Glycerol
3. Ethyl alcohol
4. Polyethylene glycol (PEG 200 and PEG 400)
77
Barbiturates are readily ________ by water
hydrolyzed
78
Digitoxin has______ water solubility
Digitoxin has poor water solubility
79
Non-aqueous vehicles Requirements
1. Non toxic in the amounts administered
2. Nonirritating
3. Non-sensitizing
4. It must not exert a pharmacological activity
80
Non-aqueous vehicles must have
1. Physical and chemical stability at various pH level
2. Viscosity (suitable for use in syringes)
3. Fluidity (must be maintained over a temperature range)
4. Boiling point (should be high to permit heat sterilization)
5. Constant purity or easy of purification
81
Fixed oils must never be administered ___ and are mostly administered __.
iv, IM
82
USP restricts oils for _________ use which do not remain clear when cooled to 10 ⁰C.
parenteral
83
Fixed oils must not contain__________ or_______, as these materials are not adsorbed by body tissue.
mineral oil or paraffin
84
Some patients exhibit _______ to specific oils. Thus, when vegetable oils are employed in parenteral products, the label must state the specific oil.
allergic reactions
85
The concentration of co-solvent used should be ________________ within the formulation but should not be irritant or toxic to the patient.
sufficient to render the drug soluble
86
Co-solvents should not be diluted with water or ___________ may occur
precipitation
87
Preservatives
are substances added to dosage forms to protect them from microbial contamination
88
USP requirement: One or more suitable antimicrobial preservatives must be added to parenteral
products that are packaged in multiple dose containers regardless of the method of sterilization, unless
a) Otherwise directed in the individual monograph
| b) Injection’s active ingredients are themselves bacteriostatic
89
What are the 5 most common antimicrobial perservatives?
```
Antimicrobial preservatives Concentration (%)
1 Benzyl alcohol 2.0
2 Methyl paraben 0.18
3 Propyl paraben 0.02
4 Phenol 0.5
5 Benzalkonium chloride 0.01
```
90
Because they may have inherent ______ for the patient, the USP prescribes maximum concentration
limits for preservatives.
toxicity
91
When are preservatives contraindicated?
- Neonates
| - Parenteral products with volume greater than 30 mL
92
When is not necessary to add a preservatives?
The preparation will be used immediately
No water is present
The pH of the medium is either 9
93
Microorganism require ______ for growth
water
94
Certain resistant molds can grow in media with pH below ________
Three
95
Properties of the ideal preservatives
- Effective at a low, nontoxic concentration against a wide variety of organisms
- Chemically stable under normal conditions of use
- Soluble at the required concentration
- Compatible with a wide variety of drugs and excipients
- Nontoxic and non-sensitizing
- Free from objectionable odor, taste, color or stinging
96
Buffering agents are used to adjust and maintain pH to increase ___ , ____ , and _____
drug stability, solubility, and absorption
97
Buffers in injections must allow ______ to change the product pH after injections
body fluids
98
The acceptable pH range of parental products is ___ to ____ for iv and ___ to ___ for other routes?
3-10
| 4-9
99
Extreme pH's may cause complications especially when _____________
administered locally in large amounts
100
pH above 10 can cause ____ while below 3 can cause______
tissue necrosis
| severe pain
101
Buffering Agents Requirements
- Ingredients to buffer of adjust pH must be nontoxic
- Agents should be nonirritating at the needed concentration
- Agents must be in sterile form or must be rendered sterile
102
Antioxidants are
substances added to dosage forms to protect them from oxidative degradation.
103
```
True antioxidants (oxygen radical scavengers)
have____________ than the drugs and are preferentially oxidized
```
lower oxidation potential
104
Examples of True anitoxidants
Butylatedhydroxyanisole (BHA)
Butylatedhydroxytoluene(BHT)
Sodium formaldehyde sulfoxylate (SFS)
Tocopherol
105
Reducing agent they _____________ that has been oxidized
reduced a drug or excipient
106
What is the another way to control oxidation in drugs?
Displacing the air (oxygen) in and above the solution by purging with an inert gas, such as
nitrogen, also can be used as means to control oxidation of a sensitive drugs.
107
Chelating Agents
compounds that form complexes with metal ions and inactivate their catalytic activity in the oxidative properties
108
____________ may be present even in high-quality compounding ingredients and on the surface of compounding equipment and packaging material.
Metal ions
109
___________ of drug in solution is mediated either by free radicals or by molecular oxygen and catalyzed by metals.
Oxidative degradation
110
______________ sequester heavy metals and prevent catalysis of oxidation reaction
chelating agents
111
___________ can be used alone or with antioxidants
chelating agents
112
_____________ Dextrose, NaCl, KCl are commonly used to achieve _________ in a parental formulation
Tonicity agents, isotonicity
113
All parenteral products must be ________.
sterile!
114
Sterility is assured by a three-step process:
| 3
- use of sterile materials and process equipment
- use of aseptic techniques in drug product manufacture
- Sterilization of post manufacture, preferably in final sealed containers
115
What are methods of sterilization?
1. Dry heat sterilization
2. Steam sterilization
3. Filtration
4. Gas sterilization
5. Radiation
116
What is dry heat sterilization?
Dry heat sterilization is conducted at 150°C to 170°C for 2 to 4 hrs
117
What are things that can be sterilized with dry heat?
Thermostablepowders, Fixed oils and Glassware
118
What are disadvantages with dry heat sterilization?
It can not be used with materials that heat sensitive
Non-uniform heat distribution
It requires higher temperature and longer exposure time
119
Steam sterilization
is carried out in an autoclave, which is airtight jacketed chamber designed to maintain a high pressure of saturated hot steam (120°C)
120
What is the rules of the autoclave?
10 lb 115.5 °C 30 min
15 lb 121.5 °C 20 min
20 lb 126.5 °C 15 min
121
What can undergo autoclave?
Materials that can withstand 120 °C and are penetrated by moisture: Solutions sealed in ampules, bulk solutions, glassware, surgical dressing…
122
What are advantages?
- With moisture, microorganism are destroyed at lower temperature
- Heat exchange by steam is more rapid than by dry heat
123
What are disadvantages?
It can not be used with materials that heat and moisture sensitive and are not penetrated by moisture (oils, fats)
124
Filtration
depends on physical removal of microorganism by absorption on the filter medium or by sieving mechanism
125
What are two ways to sterilize products with a filter?
0.22 mm To remove microorganism
| 5 mm To remove particulate matter
126
What types of solutions are good to be filtered?
Thermoliablesolutions of low viscosity
127
What are advantages to filtration?
- Simplicity and convenience
| - Ability to sterilize thermoliablematerials
128
What are disadvantages to filtration?
- Macromolecules such as proteins may be damaged by filtration
- Some filters adsorb drugs
- Time consuming for large volume solution
129
Micro-filtration (0.1 to 2 microns): removes
bacteria, fungi, bacteriophages, and parasites.
130
Ultra-filtration (0.01 to 0.1 microns): removes
viruses.
131
Nano-filtration (0.001 to 0.01 microns): removes
organic compounds in the molecular weight range of 300-1000 Da (almost all pyrogens).
132
Reverse osmosis (
virtually all viruses, bacteria, pyrogens, organic
| molecules, 90-99% of all ions.
133
Gas sterilization
is accomplished by exposure to gas (ethylene oxide) that kills microorganism
134
What does a Gas sterilization oven need to have?
Ethylene oxide concentration:500 –1000 mg/mL
Relative humidity: 30 –60 %
Temperature: 55 °C
Time: 6 hrs
135
What materials work best with Gas Sterilization?
Thermoliablepowders (e.g. penicillin), instruments, plastic syringes, needles, catheters
136
What are advantages to Gas Sterilization?
Ability to sterilize thermoliableand moisture-sensitive materials
137
What are disadvantages to Gas Sterilization?
Some drugs (e.g. thiamine, riboflavin, streptomycin) lose potency
138
____________ is accomplished by UV light or high-energy ionizing radiation such as gamma rays
Radiation sterilization
139
When is radiation sterilization good to use?
Thermoliabledrugs such as penicillin, streptomycin, thiamine, riboflavin
140
When is radiation sterilization not good to use?
highly specialized equipment required
| Some materials sensitive to irradiation
141
Parenteral products are packaged as _____ volume and _____ volume parenterals
Large and Small
142
Large volume parenteral dosage form
A single-dose injection that is intended for intravenous use and is packaged in containers labeled as containing more than 100 mL
143
Small volume parenteral dosage form
An injection packaged in containers labeled as containing 100 mL or less
144
LVP solutions are packaged in containers holding more than _____ ml.
100 ml
145
Why are plastic LVP bags good to use?
Do not break
Weigh less
Take up less storage space
146
Why are plastic LVP bags not good to use?
- Some drugs adsorb to the plastic
| - Some solutions leach a plasticizer out the plastic
147
When are glass bottles good to use for LVP?
To administer drugs that are incompatible with plastic bags
148
LVP are usually administered in volumes of 100 mL to 1L or more per day by slow IV infusion
and are commonly used for:
- Maintenance Therapy
- Replacement Therapy
- Drug Vehicle
149
Maintenance Therapy
is used for fluid and electrolyte balance
150
Replacement Therapy
is used for replacements of fluid and electrolytes
151
Drug Vehicle
for administering other drugs
152
Because of the large volumes administered, LVP must not contain_____________.
bacteriostatic agents
153
SVP solutions are usually _________ and are packaged in different containers.
100 ml or less
154
Small volume liquid parentals are usually found in _____, _______, and _______
ampules,prefilled syringes and vials
155
What are powdered drugs supplied in?
vials
156
SVP may not be isotonic because?
large volume of blood rapidly dilutes them
157
SVP's pH can vary since the blood buffering system rapidly readjusts the pH due to
small volume of Small Volume parental
158
What do Multi-dose vials usually have?
preservatives
159
The preparations of intravenous admixture
involves the addition of one or more drugs to large
| volume sterile fluids such as sodium chloride injection, dextrose injection, and TPN fluid.
160
Drug incompatibilities
refers to interactions between two or more substances which lead to changes in chemical, physical, therapeutic properties of the pharmaceutical dosage form.
161
What are two types of drug incompatibilities?
1. Physical incompatibility
| 2. Chemical incompatibility
162
The unitended precipitation and toxic products due to incompatibilities can cause
problems from thrombophlebitis to multi organ failure
163
Physical incompatibility
Interaction between two or more substances that causes change in solubility, precipitation, color, odor, viscosity, and morphology
164
What are three causes of physical incompatibility?
1. pH effect
2. Dilution of mixed solvent systems
3. Cation-anion interactions
165
may affect the safety, efficacy and appearance of pharmaceutical preparation.
Incompatibilities
166
The buffering capacity of the aqueous media of the large volume parenteral solutions is _______ and, therefore, pH changes often follow from the addition of the drugs to an infusion fluid.
small
167
Why is having a small buffering capacity a problem?
This decrease or increase in pH may then produce physical (e.g. precipitation) or chemical (e.g. hydrolysis) in the system.
168
The sodium salts of weak acids, such as phenytoin sodium or phenobarbital sodium, precipitate as _______ when added to intravenous fluids with an acidic pH.
free acids
169
Precipitation on dilution in aqueous iv fluids is common with
non-ionized drugs
170
Cation-anion interactions
Can cause Precipitation
171
______________ are the most common causes of drug incompatibility as precipitation of nonionizeddrug forms.
Acid-base reactions
172
Decomposition of a drug substance from combination of parental dosage forms is called ____________.
chemical incompatibility.
173
Most chemical incompatibilities result from:
1. oxidation
2. Hydrolysis
3. others
174
While it impossible to predict and prevent all parenteral incompatibilities, their occurrence can be ________.
minimized!
