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Questions and Answers
What is the primary purpose of sterilization in parenteral preparations?
What is the primary purpose of sterilization in parenteral preparations?
Which component ratio describes the solid phase of Insulin Lente?
Which component ratio describes the solid phase of Insulin Lente?
Which sterilization method is appropriate for heat-sensitive preparations?
Which sterilization method is appropriate for heat-sensitive preparations?
Why are antimicrobial agents used in multi-dose vials?
Why are antimicrobial agents used in multi-dose vials?
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What characteristic is NOT ideal for a preservative used in injectable formulations?
What characteristic is NOT ideal for a preservative used in injectable formulations?
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What does the absence of clarity in a parenteral preparation indicate?
What does the absence of clarity in a parenteral preparation indicate?
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What is the primary purpose of using preservatives in multi-dose injections?
What is the primary purpose of using preservatives in multi-dose injections?
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Which of the following methods cannot be used for suspensions?
Which of the following methods cannot be used for suspensions?
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Which of the following preservatives is commonly used at a concentration of 1-2% w/v in multi-dose injections?
Which of the following preservatives is commonly used at a concentration of 1-2% w/v in multi-dose injections?
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What is a primary concern regarding the presence of pathogens in parenteral preparations?
What is a primary concern regarding the presence of pathogens in parenteral preparations?
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What are foreign particles in parenteral solutions likely to cause if injected?
What are foreign particles in parenteral solutions likely to cause if injected?
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Which component is a type of pyrogen that can cause febrile reactions in patients when injected?
Which component is a type of pyrogen that can cause febrile reactions in patients when injected?
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What factors affect the intensity of the pyrogenic response in patients?
What factors affect the intensity of the pyrogenic response in patients?
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Which preservative is noted for having a concentration of 0.01% w/v in multi-dose injections?
Which preservative is noted for having a concentration of 0.01% w/v in multi-dose injections?
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In parenteral solutions, what is the main requirement concerning clarity?
In parenteral solutions, what is the main requirement concerning clarity?
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Why is benzalkonium chloride not used for injection in pharmaceutical preparations?
Why is benzalkonium chloride not used for injection in pharmaceutical preparations?
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What characteristic of pyrogens allows them to remain in water even after sterilization?
What characteristic of pyrogens allows them to remain in water even after sterilization?
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Which method is considered the most reliable for eliminating pyrogens from water?
Which method is considered the most reliable for eliminating pyrogens from water?
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Which pH value is ideal for parenteral preparations?
Which pH value is ideal for parenteral preparations?
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What is the purpose of using buffers in non-neutral parenterals?
What is the purpose of using buffers in non-neutral parenterals?
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Which source can contribute to the presence of pyrogens in sterile pharmaceutical preparations?
Which source can contribute to the presence of pyrogens in sterile pharmaceutical preparations?
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What should be avoided when formulating buffers for injection solutions?
What should be avoided when formulating buffers for injection solutions?
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What type of heat treatment is used for depyrogenation of thermostable equipment?
What type of heat treatment is used for depyrogenation of thermostable equipment?
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Which method is NOT effective for eliminating pyrogens from plastic materials?
Which method is NOT effective for eliminating pyrogens from plastic materials?
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What occurs when red blood cells are exposed to a hypotonic solution?
What occurs when red blood cells are exposed to a hypotonic solution?
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Which agent is NOT typically used for tonicity adjustment in parenteral solutions?
Which agent is NOT typically used for tonicity adjustment in parenteral solutions?
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What is the primary effect of hypertonic solutions on red blood cells?
What is the primary effect of hypertonic solutions on red blood cells?
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How can a hypertonic solution for injection be made isotonic?
How can a hypertonic solution for injection be made isotonic?
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Which of the following is a potential risk when administering hypertonic IV infusions?
Which of the following is a potential risk when administering hypertonic IV infusions?
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What is the role of electrolytes in tonicity adjustment of parenteral solutions?
What is the role of electrolytes in tonicity adjustment of parenteral solutions?
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Which statement about hypertonic solutions is false?
Which statement about hypertonic solutions is false?
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What must occur for a successful therapeutic response after parenteral administration?
What must occur for a successful therapeutic response after parenteral administration?
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What is a crucial factor influencing the absorption of a drug administered via parenteral routes?
What is a crucial factor influencing the absorption of a drug administered via parenteral routes?
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Which of the following statements about prodrugs is accurate?
Which of the following statements about prodrugs is accurate?
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Which factor does NOT affect the absorption of a drug at the injection site?
Which factor does NOT affect the absorption of a drug at the injection site?
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How does polymorphism affect drug formulations?
How does polymorphism affect drug formulations?
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Which alteration is NOT a potential advantage of drug modification in creating prodrugs?
Which alteration is NOT a potential advantage of drug modification in creating prodrugs?
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What is the main effect of pH on drug formulations?
What is the main effect of pH on drug formulations?
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Which is a common prodrug for steroids?
Which is a common prodrug for steroids?
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What is the primary consideration when ensuring adequate drug absorption at an injection site?
What is the primary consideration when ensuring adequate drug absorption at an injection site?
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What is a requirement for a liquid used in parenteral product preparations regarding its viscosity?
What is a requirement for a liquid used in parenteral product preparations regarding its viscosity?
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Which property must a non-aqueous vehicle possess to ensure it can be heat sterilized?
Which property must a non-aqueous vehicle possess to ensure it can be heat sterilized?
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Why are mixed solvent systems preferred over fixed oils in parenteral products?
Why are mixed solvent systems preferred over fixed oils in parenteral products?
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What is a key restriction on fixed vegetable oils used for parenteral products?
What is a key restriction on fixed vegetable oils used for parenteral products?
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Which of the following oils is NOT commonly used in injections?
Which of the following oils is NOT commonly used in injections?
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What must be indicated on the label when employing vegetable oils in parenteral products?
What must be indicated on the label when employing vegetable oils in parenteral products?
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What type of administration route is strictly prohibited for oleaginous injections?
What type of administration route is strictly prohibited for oleaginous injections?
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What is the major reason for using oils in injections, particularly in relation to steroids?
What is the major reason for using oils in injections, particularly in relation to steroids?
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Study Notes
Parenteral Preparations
- Parenteral preparations are administered by injection or infusion into the body tissues or blood
- Classification of parenterals includes volume-based and pharmaceutical classification
- Volume-based classification includes small volume and large volume parenteral solutions
- Pharmaceutical classification includes solutions, suspensions, emulsions, and dry powder
Solutions
- Most injectable products are solutions that are typically aqueous
- Solutions may be mixtures of water with glycols, alcohol or other non-aqueous solvents
- Viscosity and surface tension of most solutions are similar to water; however, some solutions (e.g., streptomycin sulfate injection, ascorbic acid injection) are viscous
- Parenteral solutions are usually filtered through 0.22µm membrane filters to achieve sterility and remove particulate matter
- Thermostable drug solutions should be terminally autoclave sterilized after filling to ensure sterility
Suspensions
- Suspensions are one of the most difficult parenteral dosage forms
- For insoluble drugs, particle size ranges from 5 - 10 µm
- Suspensions given via IM route and characterized by prolonged depot effect
- Drug dissolution rate in tissue fluids decreases, resulting in a decrease in absorption rate (sustained effect)
- Formulation requires balancing various factors for ease of resuspension and ejection through 18-21 gauge needles
- Factors for suspension formulation include particle size distribution, zeta potential, rheological properties, and wettability & surface tension
Emulsions
- Parenteral emulsions have several uses, including emulsions of allergens (SC), sustained-release depot preparations (IM), and rarely IV emulsions
- Parenteral emulsions should have a droplet size less than 1µm to prevent embolism
- Limited selection of stabilizers and emulsifiers limits emulsion formulations due to autoclave sterilization and injection constraints
- Unwanted physiological effects, such as pyrogenic reactions and hemolysis are a concern in emulsion formulations
Lipid Emulsions
- Lipid emulsions are a class of IV emulsions
- Fats are transported in the bloodstream as small droplets (0.5-1µm), having a central triglyceride core and outer phospholipid layer
- IV fat emulsions typically contain 10-20% oil
- These emulsions provide essential fatty acids and calories for total parenteral nutrition (TPN)
- Common components include soybean oil, safflower oil, cottonseed oil, egg phospholipids, soybean phospholipids, and soybean lecithin
Dry Powder
- Some drugs are unstable in aqueous solutions and are formulated as dry powders
- Dry powders are reconstituted with water immediately before administration
- The pharmacist must be aware of the final reconstitution volume
- Reconstituted product is typically an aqueous solution, but can also be an aqueous suspension (e.g., ampicillin trihydrate, spectinomycin hydrochloride)
- Most common form of sterile powder is freeze-dried or lyophilized powder
Advantages of Freeze Drying
- Water is removed at low temperatures, avoiding damage to heat-sensitive drugs
- Proper freeze drying creates a high surface area for rapid and complete reconstitution
- Freeze-dried dosage forms allow for precise filling of solutions into vials
- Minimizes dust containment and worker exposure to hazardous drugs
Limitations of Freeze Drying
- Some drugs (e.g., proteins, liposomal products, vaccines) can be damaged by freeze-drying
- Stability of the drug in the solid (crystalline or amorphous) state can be an issue if freeze drying produces an unstable amorphous solid
- Freeze drying can be an expensive drying procedure
Controlled Drug Delivery in Parenteral Preparations
- Controlled drug delivery is achieved by decreasing drug dissolution rates in tissue fluids, leading to decreased absorption rates and a sustained effect
- Increasing particle size (e.g., in suspensions) and increasing viscosity (e.g., with oil solutions, suspensions, or viscosity-imparting agents) can also achieve controlled drug delivery
- Implants (SC) for potent hormones, use of less soluble salts (e.g., insulin-Zn), and use of crystalline rather than amorphous forms (e.g., insulin lente) are additional methods
Insulin Lente
- Insulin zinc suspension
- Intermediate-acting porcine or human insulin with zinc salt added
- Solid phase of the suspension contains a ratio of 7:3 crystalline to amorphous insulin
Specification of Parenterals
- Key specifications include sterility, absence of pyrogens, clarity, pH, and tonicity
Sterility
- Sterility means the absence of all living microorganisms and their spores
- Sterilization methods depend on the preparation and ingredients
- Sterility testing is crucial to ensure effectiveness
- Preservatives are added to maintain sterility
Methods of Sterilization
- Typical methods include moist heat sterilization, dry heat sterilization, ionizing radiation sterilization, gaseous sterilization (ethylene oxide), and filtration
Preservation
- Antimicrobial agents are added to multi-dose vials to protect the injection from contamination
- Preservatives are usually not added to LVPs (single-dose containers) as they are discarded after use, but there are exceptions
- Preservative use may be avoided if the drug has inherent antimicrobial effect
- An ideal preservative must be effective against a wide range of bacteria, nontoxic at the used concentration, stable, and compatible with injection components.
Clarity
- Parenteral solutions must be clear and completely free of foreign particles (e.g., dust, glass, fiber) to prevent foreign body reactions (muscle granuloma or embolism).
Pyrogens
- Pyrogens are organic metabolic products from microbial contamination causing fever and other reactions in patients
- Caused by contamination with Gram-negative bacteria endotoxins (lipopolysaccharides).
- Injection of pyrogens can cause toxic effects, such as fever, chills, pain, malaise, shock, and death
Methods of Depyrogenation
- Common methods for removing pyrogens include distillation for water depyrogenation and rinsing with pyrogen-free water (for equipment) and using dry heat for thermostable equipment
pH
- The pH of blood is ~7.4, maintained by major buffer systems (carbonic acid/bicarbonate, phosphoric acid/phosphate, protein)
- Ideal pH for parenteral preparations is 7.4, however, some drugs require different pH values for stability.
- Drug solubility can depend on solution pH
Non-Neutral Parenterals
- Formulated at suitable pH for stability and solubility
- Use buffers to prevent degradation and avoid significant disturbance to body's buffer systems
- Frequent buffer systems include acetates, phosphates, and citrates
Non-Neutral LVPs
- IV infusions should avoid buffering systems to minimize toxicity
- Large volumes need large amounts of buffer which can be difficult to neutralize; hence are avoided in IV solutions
- Non-neutral IV solutions must be injected slowly to prevent major changes in blood pH due to the large volumes
Tonicity
- Isotonic solutions have the same osmotic pressure as blood plasma
- Hypertonic solutions (higher osmotic pressure than blood) can cause crenation and pain, while hypotonic solutions (lower osmotic pressure than blood) can cause lysis and hemolysis
- Tonicity adjustment to parenterals is common
Tonicity Adjustment
- Hypertonic solutions can be made isotonic through dilution
- Hypertonic solutions for IM or SC injections can still be mildly painful, so injected slowly into large veins
- In some cases, deliberately prescribed hypertonic IV infusions can be essential to patients with acute hyponatremia to raise blood sodium concentration back to normal range.
Formulation of Parenteral Products
- Successful parenteral administration depends on maintaining adequate drug concentration in the desired area of action
- Active drugs, solvents, containers, and additives are all considered during parenteral formulation
Active Drug
- No absorption step; drug absorption from the injection site is essential
- Drug solubility is crucial to injection, along with consideration of drug precipitation issues at the injection site
Prodrugs
- Chemical modifications can make drugs more stable, alter solubility, improve depot action or reduce pain
- Conversion is either within the body of reconstituted after reconstitution - an example is dry powder
Polymorphism
- Polymorphism is the existence of multiple crystal forms of a drug
- Affects solubility and dissolution rates; important to parenteral formulations
Solvents and Vehicles for Injection
- Aqueous solvents are preferred, but non-aqueous vehicles may be necessary for drugs with limited water solubility or susceptibility to hydrolysis by water
Aqueous Vehicles
- Water for injection is the most common aqueous vehicle
- It undergoes rigorous purifying process, must be sterile and pyrogen-free, packaged in single-dose containers (maximum 1 L)
- May contain antimicrobial agents (bacteriostatic) or additives depending on the preparation
Other Aqueous Vehicles
- Sodium chloride injection (sterile isotonic solution, no antimicrobial agents), Bacteriostatic sodium chloride injection (sterile isotonic solution, with antimicrobial), Ringer's Injection (sterile solution with sodium chloride, potassium chloride, calcium chloride), Lactated Ringer's injection (similar to Ringer's, but includes sodium lactate )
Non-Aqueous Vehicles
- Preferred for drugs poorly soluble in water
- Must be nonirritating, nontoxic, stable at various pH levels, have appropriate viscosity for ease of injection, and meet temperature and sterilization standards
- Primarily oil-based: including water miscible oils (water soluble), that assist in maintaining stability, and serving as stabilizers (e.g. diazepam)
Oils
- Used for sustained-release products, often with steroids
- Oil-based injections are common for IM administration but not IV.
- Oils must be clear at storage temperature, and contain no mineral oil or paraffin
- Oils must meet stability and clarity requirements.
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Description
This quiz explores the fundamentals of parenteral preparations, their classification, and key properties. Participants will learn about volume-based and pharmaceutical classifications as well as the characteristics of solutions and suspensions. Test your knowledge on the various types of injectable products and their preparation methods.
