PR5217: Injectables I

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Questions and Answers

What does a higher Cmax indicate in pharmacokinetic profiles?

Faster absorption rate (correct)

Increased tissue retention

Decreased plasma concentration

Slower absorption rate

What is the relationship between dissolution rates and absorption?

Slower dissolution increases Cmax

Dissolution rates have no impact on absorption

Faster dissolution leads to faster absorption (correct)

Faster dissolution results in slower absorption

Which statement is true regarding particle sizes entering the lymphatic system?

Particles <100 nm easily enter the lymphatic system

Particles >100 nm typically do not enter the lymphatic system (correct)

Only molecules can enter the lymphatic system regardless of size

Particles >100 nm typically enter the lymphatic system

How does the method of intravenous injection affect plasma concentration over time?

It allows for immediate peak plasma concentration Signup and view all the answers

What does AUC represent in pharmacokinetics?

The total drug exposure over time Signup and view all the answers

What is the primary purpose of implants in pharmacology?

To release active substances over an extended period Signup and view all the answers

Which of the following statements about sterility in injectable preparations is true?

Chemicals can be used to achieve sterility. Signup and view all the answers

Which type of sterilization is best suited for aqueous, thermostable solutions?

Moist heat sterilization Signup and view all the answers

What does the Sterility Assurance Level indicate?

The probability of the presence of microorganisms in drug products Signup and view all the answers

How is energy transferred in moist heat sterilization?

Primarily through evaporation and recondensation Signup and view all the answers

What is the volume of distribution and its significance in pharmacokinetics?

The volume of distribution is a pharmacokinetic parameter indicating the presence of the drug in blood plasma, reflecting how extensively the drug disperses into body tissues. Signup and view all the answers

How do liposomal formulations like MyocetTM and DoxilTM differ in terms of unbound doxorubicin?

MyocetTM contains a large amount of unbound doxorubicin, while DoxilTM comprises almost no unbound doxorubicin. Signup and view all the answers

What are the implications of a drug's tolerance to particles or pH variations in SC/IM administration?

A higher tolerance to particles or pH variations in subcutaneous (SC) or intramuscular (IM) administration allows for safer and more effective delivery of biologics. Signup and view all the answers

Why are intravenous (IV) injections significant in determining the volume of distribution for drugs?

IV injections deliver drugs directly into the bloodstream, allowing for accurate assessment of how the drug distributes in the circulatory system. Signup and view all the answers

Discuss the distribution characteristics of doxorubicin and their implications in chemotherapy.

Doxorubicin's distribution into tissues varies markedly, influencing its efficacy and safety profile, particularly in formulations with different unbound doxorubicin levels. Signup and view all the answers

Study Notes

Course Information

Course name: PR5217: Injectables 1
Instructor: Associate Professor Matthias G. Wacker, PhD
Department: Department of Pharmacy, Faculty of Science
Contact: [email protected]
University: National University of Singapore (NUS)

Learning Objectives

Understand how different injection sites affect drug performance
Identify regulatory requirements for parenteral products
Explain the roles of excipients in various injectables
Describe the processes used for sterilizing liquids and solids in drug products

Parenteral Drug Delivery

Often an invasive treatment requiring healthcare professionals
Frequently used in emergencies for rapid drug delivery with immediate onset of action
Sometimes used to formulate depot formulations of degradable and poorly permeable compounds
Very high cost of production due to sterility requirements (clean room or closed process)

Parenteral Preparations

Sterile preparations administered via injection, infusion, or implantation
Examples of types: injections, infusions, concentrates, powders, implants

Injection Sites

Intravenous (IV) administration has stricter requirements compared to subcutaneous (SC) or intramuscular (IM) injections
SC/IM have greater tolerance for particles, oily liquids, hypotonic or hypertonic solutions, and pH variations

Volume of Distribution

Pharmacokinetic parameter indicating the presence of a drug in blood plasma
IV injections are commonly used to determine distribution volume

IV Injection Case Study: Liposomes

Myocet™ has more unbound doxorubicin compared to Doxil™ compared to conventional doxorubicin.

Influence of Biologics

Parenteral route accounts for 92% of administrations
Oral, topical, subcutaneous, and other routes account for the rest of the percentages (oral and topical both constitute a small part) of routes

Subcutaneous Tissue

Explains the process of drug release, metabolism, and tissue retention following injection.

Pharmacokinetic Profiles

Plasma concentrations provide insights into the extent and rate of drug absorption
Cmax and AUC (area under the curve) are key parameters used to evaluate these absorption parameters.

Dissolution

Poorly soluble drugs with varying particle sizes affect dissolution rates, which in turn influence the speed of drug absorption (measured by Cmax and AUC).

Excipients - Tonicity

Sodium chloride and buffer salts (e.g., histidine, citrate, phosphate) are used to adjust tonicity
Small molecules (e.g., dextrose, glucose, mannitol, sorbitol) are also used

Excipients - pH

Buffered solutions (phosphate, acetate, citrate, histidine) are used to maintain pH
Sodium hydroxide and hydrochloric acid are used for pH adjustment

Excipients - Stabilization

Surfactants (polysorbate, poloxamer), and steric stabilizers (dextran, albumin), are used for physical stability
Antioxidants (ascorbic acid) are used for chemical stability
Preservatives (metacresol) are used for microbiological stability

Insulin Solution

Includes zinc chloride, glycerol, metacresol, sodium hydroxide, hydrochloric acid, and water for injections as excipients

Infusions

Sterile, aqueous solutions or emulsions primarily intended for large-volume administration
No preservatives are generally added
Solutions and emulsions are practically free of particles and do not show any phase separation, and all infusions must be tested for pyrogens.

Concentrates for Injections or Infusions

Sterile solutions intended for dilution and use
Prepared in prescribed volumes

Antibody Concentrate

Contains polysorbate 80, sodium chloride, tri-sodium citrate dihydrate, and water for injections

Powder for Injections or Infusions

Sterile solid substances that readily form clear or uniform suspensions.
Often made via freeze-drying.
Additional excipients aid in the drying process

Implants

Sterile, solid preparations designed for implantation and sustained-release drug delivery
Methods of manufacture includes hot melt extrusion

Sterility

Sterility and the absence of pyrogens are essential requirements of all injectable preparations.

Sterility Testing

The testing is summarized by the pharmacopeia and filtration method is use to count microorganisms

Pyrogens

Historical development of pyrogen testing methods, including RPT (Hort & Penfold), LAL, and MAT

Sterilization Methods (Moist Heat Sterilization)

Achieved using saturated steam under pressure
Suitable for aqueous and thermostable solutions, as well as lab instruments.

Sterilization Methods (Dry Heat Sterilization)

Suitable for thermostable powders, water-free, thermostable ointments and other objects (dishes, etc.)

Sterilization Methods (Gamma Radiation Sterilization)

Utilize gamma radiation for sterilization.
The process involves a specific product packaging and treatment procedure.

Summary

Injectables, with varying characteristics, encompass a wide range of administration sites and preparations
The pharmacopeia categorizes preparations based on their tolerance regarding pH, particle concentration, tonicity.
Key considerations include preparing injectable formulations that are sterile and free from pyrogens, and ensuring stability (physical, chemical, and microbiological)

Thermodox®

Rapid doxorubicin release triggered by heat
Combining radiation therapy with specific liposomal delivery for tumor targeting.
Preclinical findings do not always translate into clinical efficacy improvements.

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Description

This quiz covers essential concepts of parenteral drug delivery, focusing on injection sites, regulatory requirements, excipient roles, and sterilization processes. It aims to deepen the understanding of injectable preparation and performance in healthcare settings.