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Questions and Answers
What phase involves the development of a drug into a successful delivery system?
What phase involves the development of a drug into a successful delivery system?
Which factor is NOT a barrier during the pharmaceutical phase?
Which factor is NOT a barrier during the pharmaceutical phase?
In which phase does drug receptor interaction occur?
In which phase does drug receptor interaction occur?
What can limit the absorption of a drug in the pharmacokinetic phase?
What can limit the absorption of a drug in the pharmacokinetic phase?
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Which method can be used to improve drug passive absorption through biological membranes?
Which method can be used to improve drug passive absorption through biological membranes?
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Which of the following is a potential barrier in the pharmacokinetic phase?
Which of the following is a potential barrier in the pharmacokinetic phase?
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What is a common characteristic of unionized drugs in terms of absorption?
What is a common characteristic of unionized drugs in terms of absorption?
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Which statement accurately describes the pharmacodynmic phase?
Which statement accurately describes the pharmacodynmic phase?
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When selecting a prodrug linkage, which factor is crucial?
When selecting a prodrug linkage, which factor is crucial?
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Which barrier is associated with the pharmaceutical phase?
Which barrier is associated with the pharmaceutical phase?
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What type of prodrug derivatives improve absorption and the duration of action?
What type of prodrug derivatives improve absorption and the duration of action?
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What is a characteristic of the pharmacokinetic phase?
What is a characteristic of the pharmacokinetic phase?
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Which prodrug derivative has limited applications due to its relative stability in vivo?
Which prodrug derivative has limited applications due to its relative stability in vivo?
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What is a primary reason for poor drug absorption?
What is a primary reason for poor drug absorption?
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Which enzyme is responsible for hydrolyzing azo products?
Which enzyme is responsible for hydrolyzing azo products?
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What property of dopamine causes it to poorly cross the blood-brain barrier?
What property of dopamine causes it to poorly cross the blood-brain barrier?
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Which of the following is NOT a problem that the prodrug approach aims to overcome?
Which of the following is NOT a problem that the prodrug approach aims to overcome?
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Which factor is essential to consider before synthesizing a prodrug?
Which factor is essential to consider before synthesizing a prodrug?
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What is a requirement for a prodrug to be effective?
What is a requirement for a prodrug to be effective?
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What is a primary consideration when choosing a derivative for a prodrug?
What is a primary consideration when choosing a derivative for a prodrug?
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Rapid generation of the parent drug is especially important when aiming to:
Rapid generation of the parent drug is especially important when aiming to:
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Which of the following is a key characteristic of prodrugs regarding their behavior in the body?
Which of the following is a key characteristic of prodrugs regarding their behavior in the body?
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Which chemical modification is most likely to improve a drug’s solubility?
Which chemical modification is most likely to improve a drug’s solubility?
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To reduce injection pain in a prodrug design, it is important to consider:
To reduce injection pain in a prodrug design, it is important to consider:
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What characteristic of covalent binding makes it advantageous for drug-carrier complexes?
What characteristic of covalent binding makes it advantageous for drug-carrier complexes?
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Which property of non-specific carriers influences their distribution in the body?
Which property of non-specific carriers influences their distribution in the body?
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In the context of cross-linking reactions for drug delivery, which is a desirable characteristic?
In the context of cross-linking reactions for drug delivery, which is a desirable characteristic?
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What diameter of carriers generally targets the liver, spleen, and kidney for distribution?
What diameter of carriers generally targets the liver, spleen, and kidney for distribution?
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What is a disadvantage of non-covalent cross-linking when used in drug delivery systems?
What is a disadvantage of non-covalent cross-linking when used in drug delivery systems?
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What is the primary purpose of using biological carriers in drug delivery?
What is the primary purpose of using biological carriers in drug delivery?
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Which of the following is NOT a characteristic that a drug-carrier system must possess?
Which of the following is NOT a characteristic that a drug-carrier system must possess?
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What is a key benefit of drug targeting through biological carriers?
What is a key benefit of drug targeting through biological carriers?
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Which of these biological carriers is effective in drug targeting due to its ability to bind to specific cell surface receptors?
Which of these biological carriers is effective in drug targeting due to its ability to bind to specific cell surface receptors?
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Which of the following drugs can be incorporated into biological carriers?
Which of the following drugs can be incorporated into biological carriers?
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What type of carrier is characterized by a lack of specific binding to cell surface receptors?
What type of carrier is characterized by a lack of specific binding to cell surface receptors?
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Why is biocompatibility an important characteristic of drug-carrier systems?
Why is biocompatibility an important characteristic of drug-carrier systems?
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What is a potential advantage of combining drug carriers with antibodies?
What is a potential advantage of combining drug carriers with antibodies?
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What is the primary reason L-dopa is effective in treating Parkinson's disease?
What is the primary reason L-dopa is effective in treating Parkinson's disease?
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How does increasing the water solubility of allopurinol affect its absorption?
How does increasing the water solubility of allopurinol affect its absorption?
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Why was 2-(p-acetaminophenoxy) tetra-hydropyran developed as a prodrug of acetaminophen?
Why was 2-(p-acetaminophenoxy) tetra-hydropyran developed as a prodrug of acetaminophen?
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What property of methenamine makes it suitable as a prodrug for formaldehyde?
What property of methenamine makes it suitable as a prodrug for formaldehyde?
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What is the goal of acylating the 17-B-hydroxy group in testosterone therapy?
What is the goal of acylating the 17-B-hydroxy group in testosterone therapy?
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How does preparing slightly soluble salts of penicillin solve its stability issue?
How does preparing slightly soluble salts of penicillin solve its stability issue?
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What advantage does dipivefrin provide in the treatment of glaucoma?
What advantage does dipivefrin provide in the treatment of glaucoma?
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Which statement about prodrugs is true?
Which statement about prodrugs is true?
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Study Notes
Chapter 2: Drug Delivery Approaches
- This chapter covers approaches in drug delivery
- Course: Drug Delivery Systems
- Course Code: 070114120
- Fall 2023
- Instructor: Msc Suhad Anabousi
- University: Arab American University, Palestine
Approaches in Drug Delivery
- Chemical Approach/Prodrugs
- Used for drug optimization through chemical modification
- Two common chemical derivatives used for modification
- Analogs
- New drugs with new pharmacological and pharmacokinetic characteristics (e.g., fentanyl vs. morphine)
- Prodrugs
- Same pharmacological characteristics as parent compounds, but different pharmacokinetic properties (delivering the drug itself)
- Analogs
- Biological Approach
- Involves using biological materials for controlled drug delivery
- Effective drug targeting and side effect reduction
- Biological carriers (e.g., albumin, antibodies, DNA, lipoproteins, glycoproteins) are used
- Methotrexate and Adriamycin are examples of drugs incorporated into these carriers
- Carriers are used for enhancing drug effectiveness in the body
- Polymeric Approach
- Also discussed in the presentation
Prodrugs
- Defined as an alteration in the physicochemical properties of a drug via bio-reversible chemical modification
- The prodrug is inactive, and the parent drug is regenerated in vivo
- It's used to overcome barriers that hinder a drug from reaching its target site
- The drug is modified chemically to improve its usefulness
Drug Action & Barriers
- Pharmaceutical phase: In vitro analysis of drug development
- Pharmacokinetic phase: After drug administration in the body, its fate is analyzed.
- Incomplete absorption can be affected by dosage form factors and physicochemical properties
- Can cause transport problems across membranes (GI, other membranes)
- Poor drug solubility
- Pharmacodynamic phase: Interaction between the drug and target receptors
- Prodrugs can overcome barriers in the pharmaceutical stage and pharmacokinetic phase, but they do not affect the pharmacodynamic stage.
- Important to analyze drug action and how barriers might affect its usefulness
Drug Action & Barriers (continued)
- Pharmaceutical phase:
- Deals with drug development into a delivery system
- Includes economics and drug formulation aesthetics (appearance, taste)
- Barriers that represent issues in developing the formulation
- Taste, pain (injection), texture (skin delivery )
- Volatile drugs, heat-sensitive drugs, photosensitive ones
- Pharmacokinetic phase:
- This deals with the fate of a drug after administration
- Incomplete absorption of the drug due to:
- Dosage form properties
- Properties of the drug
- Other membranes in the body.
- Drugs are metabolized early (before circulation)
- Toxicity during distribution to tissues or organs
- Poor site specificity of the drug
Pharmacodynmic phase
- This focuses on the drug-receptor interactions, and not the drug delivery or the process of drug getting to the targeted location
- This is about how the drug works once it reaches its target.
The Prodrug Approach
- Used to overcome issues with drug molecules:
- Absorption problems
- Solubility problems
- Toxicity problems
- Formulation and stability issues
Synthesis of Prodrugs
- Before synthesizing a prodrug consider:
- Modifying functional groups of the parent drug
- Alcoholic, hydroxyl, thiol, and carboxylic acid groups
- Availability of synthetic methods
- Cost-effectiveness of the chemical intermediaries used in synthesis
- Modifying functional groups of the parent drug
Synthesis of Prodrugs (continued)
- Design considerations include:
- Optimal synthesis and purification steps (ideally a minimal number of steps)
- Chemical stability of the prodrug in its bulk form, along with the compatibility of the prodrug with the drug formulation itself.
- Toxicity of the prodrug's derivative component
- Bioreversibility of the prodrug in vivo (conversion back to the parent drug)
The Choice of a Derivative
- Physicochemical properties (prodrug design):
- Masking bitter taste or odors
- Improving absorption
- Pain reduction during injections
- Rapid or decreased gastric distress
- Short half-life is needed for prodrugs to ensure they degrade quickly after passing barriers/ reaching their target location (short half-life in prodrugs reduces the need for prodrug to be active or be in use for a long time before working).
The Choice of a Derivative (continued)
- Modified physicochemical and pharmacological properties (e.g., enhancing drug bioavailability related to poor water solubility):
- Phosphate esters (enhancing water solubility)
- Adding bulky hydrophobic groups, which reduces water solubility
- In general, increasing hydrophobic groups (with -CH2 units) reduces the water solubility
The Choice of a Derivative (continued)
- Drug molecule may undergo hydrolysis in specific locations, so these factors must be considered when a drug needs to be administered in specific locations for its effectiveness
- Using amides and phosphamides:
- In the case of cancer treatment, there has been an effort to use amides because these can target cancer cells.
The Choice of a Derivative (continued)
- In cases where a drug is meant to undergo slow hydrolysis or provide depot activity
- Long aliphatic chains and sterically hindered derivatives In cases where drugs need a specific amount of absorption in tissues
- Adjusted HLB (hydrophilic-lipophilic balance) in order to enhance partitioning between biological membranes and water
- Drug ionization may be altered (e.g., using hydrophobic moieties) to improve absorption in biological membranes
Selection of a Prodrug Linkage
- Requires understanding of enzymes/enzyme systems that catalyze prodrug hydrolysis
- Different enzymes active in the gut, liver, and blood of the body.
- Site-activated prodrugs: tailored for specific target tissue
Prodrug Derivatives
- Include:
- Aliphatic and aromatic esters (improving absorption and duration of action)
- Carbonate esters (rapid hydrolysis)
- Hemiesters (increased water solubility)
- Phosphate esters (high water solubility, used for localization of action)
- Amides (relative stability in vivo)
- Peptides (hydrolyzed by peptidases/proteolytic enzymes)
- Azo products (hydrolyzed by azo reductases, often used in colon)
- Phosphamides (cancer chemotherapy, selective activity on receptors)
Prodrug Examples
- Overcoming absorption problems:
- Poor lipid solubility, very low water solubility
- First-pass metabolism (the initial metabolism of a drug when it first enters the body) should be addressed or bypassed
- Poor patient acceptance:
- Unpleasant taste (e.g. acetaminophen)
- Chewing tablets for pediatric patients (conversion to better prodrug form under acidic stomach conditions), making it more compatible with the stomach
Prodrug Examples (continued)
- Site-specific delivery:
- Formaldehyde and its prodrug Methenamine (site-specific for urinary tract)
- Prolonging and Sustaining drug release (in prolonging the action to provide longer duration of action):
- Steroid therapy (e.g., testosterone), acylation of hydroxyl group
Prodrug Examples (continued)
- Stability and formulation issues:
- Penicillins (instability in aqueous solutions due to B-lactam ring hydrolysis)
- Improving efficacy of ophthalmic drugs
- Dipivefrin (prodrug of epinephrine)
II. The Biological Approach
- Includes using biological materials for controlled drug delivery
- Targeting drugs to biological carriers to enhance effectiveness and reduce side effects:
- Albumin, antibodies (IgG), lipoproteins, DNA, glycoproteins
- Drugs incorporated into biological carriers: methotrexate and Adriamycin, enzymes, nucleic acids.
Drug Carriers
- Localized drug action by introducing the carrier into the target organ
- Controlled drug release
- Drug targeting
- Protection from degradation
- Reduced nonspecific cytotoxicity
- Modified solubility, antigenicity of enzymes
- Combination of drug carriers with antibodies to develop more specific target drug carrier complexes (e.g. liposomes)
Properties of a Carrier System
- General characteristics are necessary for a drug-carrier system
- The carrier must retain the agentís activity at the site of action
- Biocompatible (nontoxic, nonimmunogenic)
- Biodegradable
- Retains its desirable characteristics in a conjugated form
Types of Carriers
- Specific carriers (high specific binding to cell surface receptors, used to direct drugs or enzymes to cells with specific receptors, such as antibodies)
- Non-specific carriers (do not have high specificity of binding, usually taken up by phagocytosis -cells in the body and blood stream take up the drug and other material, cells that take up unwanted material or material not required by the body should absorb that material - macrophages)
Example: Phagocytosis of Micro-Particles
- SEM images showing phagocytosis of microparticles by macrophages
Types of Carriers (continued)
- Cross-linking between carrier and drug molecules can be:
- Covalent binding (strong bonding, low leakage, but may delay release)
- Non-covalent binding (easier but higher leakage)
Types of Carriers (continued)
- Desirable characteristics for cross-link reactions:
- Effective control of the drug-carrier complex size
- Maintaining the target specificity of the carrier
- Maintaining the normal activity of the drug or enzyme
- Readily broken for drug release
Distribution of Non-Specific Carriers
- Distribution depends on:
- Size and size distribution of the carrier
- Lipophilicity/hydrophilicity of the carrier
- Surface charge of the carrier
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Description
Test your knowledge on the various phases of drug development in pharmaceutical sciences. This quiz covers topics like drug delivery systems, pharmacokinetics, and pharmacodynamics. Explore the barriers and characteristics that affect drug absorption and interaction.
