Podcast
Questions and Answers
Considering the intricacies of ophthalmic drug delivery and the inherent properties of dexamethasone-sodium phosphate, under what specific circumstances would a formulation scientist strategically opt for this compound despite its limited lipid solubility and consequent absorption challenges?
Considering the intricacies of ophthalmic drug delivery and the inherent properties of dexamethasone-sodium phosphate, under what specific circumstances would a formulation scientist strategically opt for this compound despite its limited lipid solubility and consequent absorption challenges?
- When immediate, localized surface action is paramount, mitigating systemic exposure risks associated with highly permeable alternatives. (correct)
- When the target pathology is confined to the corneal epithelium, capitalizing on the drug's enhanced penetration through this specific tissue layer.
- When a sustained-release mechanism is desired, leveraging the compound's reduced permeability to maintain prolonged drug levels in the aqueous humor.
- When co-administering with a potent cytochrome P450 inhibitor that selectively enhances dexamethasone-sodium phosphate metabolism.
Given that many drugs used in ophthalmic preparations are weak bases formulated as acidic salts (e.g., Pilocarpine-HCl, Atropine-SO4), what is the most critical rationale behind this specific formulation strategy, considering the physiological environment of the eye?
Given that many drugs used in ophthalmic preparations are weak bases formulated as acidic salts (e.g., Pilocarpine-HCl, Atropine-SO4), what is the most critical rationale behind this specific formulation strategy, considering the physiological environment of the eye?
- To minimize the drug's interaction with lysozyme and other tear proteins, which could lead to enzymatic degradation and reduced therapeutic efficacy.
- To ensure optimal drug solubility and stability in the aqueous tear film, which maintains a slightly alkaline pH, preventing precipitation and promoting bioavailability. (correct)
- To enhance the drug's permeability across lipophilic membranes by promoting a transient, localized increase in pH at the site of administration.
- To facilitate the drug's binding affinity to melanin within the iris, thereby prolonging its duration of action and reducing the frequency of administration.
In circumstances characterized by compromised lacrimal gland function leading to chronic keratoconjunctivitis sicca, what advanced biopharmaceutical strategy could be implemented to emulate the protective and lubricating functionalities of natural lacrimal fluid, thereby restoring ocular surface homeostasis?
In circumstances characterized by compromised lacrimal gland function leading to chronic keratoconjunctivitis sicca, what advanced biopharmaceutical strategy could be implemented to emulate the protective and lubricating functionalities of natural lacrimal fluid, thereby restoring ocular surface homeostasis?
- Topical application of a cross-linked hyaluronan hydrogel containing encapsulated growth factors to promote corneal epithelial regeneration and goblet cell proliferation. (correct)
- Systemic administration of immunosuppressants combined with somatostatin analogues to suppress lacrimal gland inflammation and stimulate tear production.
- Sustained delivery of recombinant human lysozyme via genetically engineered corneal epithelial cells to augment the eye's inherent antimicrobial defenses.
- Chronic administration of hypotonic saline solutions supplemented with mucolytic agents to promote tear film spreading and reduce surface tension.
Given the physiological constraints of the eye, particularly the limited volume it can accommodate, what sophisticated formulation technique might be employed to maximize drug retention and minimize systemic absorption following topical ophthalmic administration, especially for a drug with a narrow therapeutic index?
Given the physiological constraints of the eye, particularly the limited volume it can accommodate, what sophisticated formulation technique might be employed to maximize drug retention and minimize systemic absorption following topical ophthalmic administration, especially for a drug with a narrow therapeutic index?
Considering the unique properties of oily ophthalmic solutions, especially those utilizing castor oil, what specific biophysical mechanism accounts for their ability to prolong drug duration of action despite potentially causing transient visual disturbances?
Considering the unique properties of oily ophthalmic solutions, especially those utilizing castor oil, what specific biophysical mechanism accounts for their ability to prolong drug duration of action despite potentially causing transient visual disturbances?
In the formulation of aqueous ophthalmic solutions, what strategic manipulation of the solution's physicochemical properties would most effectively mitigate the risk of corneal irritation while simultaneously enhancing drug bioavailability, particularly for compounds exhibiting poor corneal permeability?
In the formulation of aqueous ophthalmic solutions, what strategic manipulation of the solution's physicochemical properties would most effectively mitigate the risk of corneal irritation while simultaneously enhancing drug bioavailability, particularly for compounds exhibiting poor corneal permeability?
Given the inherent challenges in formulating ophthalmic suspensions, particularly in maintaining particle size uniformity and preventing particle aggregation, what advanced microfluidic technique could be employed to generate monodisperse drug nanocrystals that exhibit enhanced ocular bioavailability and reduced irritation potential?
Given the inherent challenges in formulating ophthalmic suspensions, particularly in maintaining particle size uniformity and preventing particle aggregation, what advanced microfluidic technique could be employed to generate monodisperse drug nanocrystals that exhibit enhanced ocular bioavailability and reduced irritation potential?
Given the physicochemical properties outlined, what is the most critical consideration when selecting between CFC-11 and CFC-12 for a novel aerosol formulation intended for pulmonary drug delivery, assuming both exhibit comparable drug solubility?
Given the physicochemical properties outlined, what is the most critical consideration when selecting between CFC-11 and CFC-12 for a novel aerosol formulation intended for pulmonary drug delivery, assuming both exhibit comparable drug solubility?
In the context of developing a metered-dose inhaler (MDI) using HFA-227 and HFA-134a, which of the following strategies would most effectively mitigate the 'poor solvent' disadvantage associated with these hydrofluoroalkanes, while simultaneously accounting for potential valve lubrication issues?
In the context of developing a metered-dose inhaler (MDI) using HFA-227 and HFA-134a, which of the following strategies would most effectively mitigate the 'poor solvent' disadvantage associated with these hydrofluoroalkanes, while simultaneously accounting for potential valve lubrication issues?
Considering the listed properties of compressed gas propellantsspecifically carbon dioxide ($CO_2$) and nitrous oxide ($N_2O$)and their application in a dry powder inhaler (DPI), what adjustments would be MOST crucial to ensure consistent dose delivery across a range of ambient temperatures ($15^\circ C$ to $35^\circ C$), given the absence of a liquid phase?
Considering the listed properties of compressed gas propellantsspecifically carbon dioxide ($CO_2$) and nitrous oxide ($N_2O$)and their application in a dry powder inhaler (DPI), what adjustments would be MOST crucial to ensure consistent dose delivery across a range of ambient temperatures ($15^\circ C$ to $35^\circ C$), given the absence of a liquid phase?
When formulating a suspension-based pressurized metered-dose inhaler (pMDI), what is the MOST critical factor influencing the in vivo performance and lung deposition of the active pharmaceutical ingredient (API), considering the interplay between surfactant properties, particle size, and aerodynamic characteristics?
When formulating a suspension-based pressurized metered-dose inhaler (pMDI), what is the MOST critical factor influencing the in vivo performance and lung deposition of the active pharmaceutical ingredient (API), considering the interplay between surfactant properties, particle size, and aerodynamic characteristics?
In the development of a novel nebulizer formulation containing a macromolecular therapeutic, what is the MOST critical consideration concerning the choice of surfactant with respect to maintaining protein integrity and ensuring efficient aerosolization?
In the development of a novel nebulizer formulation containing a macromolecular therapeutic, what is the MOST critical consideration concerning the choice of surfactant with respect to maintaining protein integrity and ensuring efficient aerosolization?
A novel ophthalmic drug, exhibiting optimal stability at a pH of 7.4, is formulated as a solution. However, upon autoclaving, a precipitate forms, identified as the drug undergoing base-catalyzed degradation. Which of the following represents the MOST judicious reformulation strategy, considering both stability and sterilization requirements?
A novel ophthalmic drug, exhibiting optimal stability at a pH of 7.4, is formulated as a solution. However, upon autoclaving, a precipitate forms, identified as the drug undergoing base-catalyzed degradation. Which of the following represents the MOST judicious reformulation strategy, considering both stability and sterilization requirements?
An ophthalmic formulation of pilocarpine is being developed. Considering pilocarpine's known susceptibility to degradation at both low and high pH, which of the following strategies represents the MOST comprehensive approach to ensure optimal drug stability and patient comfort?
An ophthalmic formulation of pilocarpine is being developed. Considering pilocarpine's known susceptibility to degradation at both low and high pH, which of the following strategies represents the MOST comprehensive approach to ensure optimal drug stability and patient comfort?
Considering the biopharmaceutical challenges associated with non-systemic drug delivery, which formulation strategy would most effectively mitigate mucociliary clearance in the respiratory tract while ensuring sustained local drug concentration for a novel anti-inflammatory peptide?
Considering the biopharmaceutical challenges associated with non-systemic drug delivery, which formulation strategy would most effectively mitigate mucociliary clearance in the respiratory tract while ensuring sustained local drug concentration for a novel anti-inflammatory peptide?
A research team is developing an ophthalmic suspension of a novel corticosteroid with poor aqueous solubility. After autoclaving, they observe significant caking and difficulty in resuspension. Which of the following alteration of the formulation is MOST likely to resolve this issue while maintaining drug bioavailability and sterility?
A research team is developing an ophthalmic suspension of a novel corticosteroid with poor aqueous solubility. After autoclaving, they observe significant caking and difficulty in resuspension. Which of the following alteration of the formulation is MOST likely to resolve this issue while maintaining drug bioavailability and sterility?
In the context of personalized medicine and considering inter-individual variability in nasal drug absorption, what analytical technique would be most appropriate to predict the bioavailability of a novel antihistamine administered intranasally, accounting for variations in nasal mucosal thickness, ciliary beat frequency, and enzymatic activity?
In the context of personalized medicine and considering inter-individual variability in nasal drug absorption, what analytical technique would be most appropriate to predict the bioavailability of a novel antihistamine administered intranasally, accounting for variations in nasal mucosal thickness, ciliary beat frequency, and enzymatic activity?
A compounded ophthalmic solution contains sulphacetamide sodium (an acidic drug), edetate disodium, and benzalkonium chloride in a phosphate buffer at pH 7.4. Upon storage, a white precipitate is observed. Which of the following is the MOST probable cause of this incompatibility?
A compounded ophthalmic solution contains sulphacetamide sodium (an acidic drug), edetate disodium, and benzalkonium chloride in a phosphate buffer at pH 7.4. Upon storage, a white precipitate is observed. Which of the following is the MOST probable cause of this incompatibility?
A pharmaceutical company is scaling up the production of an ophthalmic suspension containing a novel, poorly soluble drug. During pilot-scale manufacturing, they observe significant variations in particle size distribution and settling rates between batches. Which of the following strategies would BEST ensure batch-to-batch uniformity and long-term physical stability of the suspension?
A pharmaceutical company is scaling up the production of an ophthalmic suspension containing a novel, poorly soluble drug. During pilot-scale manufacturing, they observe significant variations in particle size distribution and settling rates between batches. Which of the following strategies would BEST ensure batch-to-batch uniformity and long-term physical stability of the suspension?
A pharmaceutical company is developing a novel inhaled corticosteroid for the treatment of severe asthma. During clinical trials, a subset of patients exhibits paradoxical bronchospasm immediately following drug administration. Which of the following formulation modifications would be the MOST appropriate next step to mitigate this adverse effect, considering the potential mechanisms involved?
A pharmaceutical company is developing a novel inhaled corticosteroid for the treatment of severe asthma. During clinical trials, a subset of patients exhibits paradoxical bronchospasm immediately following drug administration. Which of the following formulation modifications would be the MOST appropriate next step to mitigate this adverse effect, considering the potential mechanisms involved?
An investigation into the diminished efficacy of a compounded ophthalmic solution of prednisolone acetate reveals that the drug is present in a polymorphic form exhibiting significantly lower dissolution kinetics than the originally specified form. Which of the following represents the MOST effective strategy for rectifying this issue and ensuring consistent drug bioavailability?
An investigation into the diminished efficacy of a compounded ophthalmic solution of prednisolone acetate reveals that the drug is present in a polymorphic form exhibiting significantly lower dissolution kinetics than the originally specified form. Which of the following represents the MOST effective strategy for rectifying this issue and ensuring consistent drug bioavailability?
A researcher is investigating the use of intra-vaginal drug delivery for a novel peptide-based antiviral agent aimed at preventing HIV transmission. Given the complex interplay of vaginal fluid dynamics, enzymatic degradation, and epithelial barrier properties, which formulation strategy would be optimal to maximize drug bioavailability and efficacy in vivo?
A researcher is investigating the use of intra-vaginal drug delivery for a novel peptide-based antiviral agent aimed at preventing HIV transmission. Given the complex interplay of vaginal fluid dynamics, enzymatic degradation, and epithelial barrier properties, which formulation strategy would be optimal to maximize drug bioavailability and efficacy in vivo?
In the design of a novel nasal spray formulation for delivering a highly lipophilic neurotherapeutic drug directly to the brain via the olfactory pathway, which excipient characteristic is MOST critical for enhancing drug transport across the nasal mucosa and into the central nervous system, while minimizing systemic exposure?
In the design of a novel nasal spray formulation for delivering a highly lipophilic neurotherapeutic drug directly to the brain via the olfactory pathway, which excipient characteristic is MOST critical for enhancing drug transport across the nasal mucosa and into the central nervous system, while minimizing systemic exposure?
A research formulation for an ophthalmic drug requires a viscosity-enhancing agent that is also biocompatible and non-irritating. You have narrowed your choices to methylcellulose, polyvinyl alcohol (PVA), and polyvinylpyrrolidone (PVP). Considering their distinct physicochemical properties, which of the following rationales BEST justifies selecting PVA for this particular application?
A research formulation for an ophthalmic drug requires a viscosity-enhancing agent that is also biocompatible and non-irritating. You have narrowed your choices to methylcellulose, polyvinyl alcohol (PVA), and polyvinylpyrrolidone (PVP). Considering their distinct physicochemical properties, which of the following rationales BEST justifies selecting PVA for this particular application?
Considering the limitations of rectal drug absorption due to factors like first-pass metabolism and variable rectal fluid volume, which formulation strategy would be most effective for delivering a therapeutic protein rectally to achieve systemic bioavailability comparable to intravenous administration?
Considering the limitations of rectal drug absorption due to factors like first-pass metabolism and variable rectal fluid volume, which formulation strategy would be most effective for delivering a therapeutic protein rectally to achieve systemic bioavailability comparable to intravenous administration?
During the development of a novel ophthalmic suspension, it is observed that the drug particles exhibit a strong tendency to aggregate due to hydrophobic interactions. Which of the following strategies represents the MOST effective approach to mitigate this aggregation while preserving the suspension's stability and bioavailability?
During the development of a novel ophthalmic suspension, it is observed that the drug particles exhibit a strong tendency to aggregate due to hydrophobic interactions. Which of the following strategies represents the MOST effective approach to mitigate this aggregation while preserving the suspension's stability and bioavailability?
A generic drug manufacturer seeks to develop an ophthalmic ointment formulation of erythromycin. The innovator product utilizes a specific grade of petrolatum known for its exceptional purity and low content of polycyclic aromatic hydrocarbons (PAHs). To ensure bioequivalence and minimize potential ocular irritation, which of the following strategies is MOST critical for the generic manufacturer to implement?
A generic drug manufacturer seeks to develop an ophthalmic ointment formulation of erythromycin. The innovator product utilizes a specific grade of petrolatum known for its exceptional purity and low content of polycyclic aromatic hydrocarbons (PAHs). To ensure bioequivalence and minimize potential ocular irritation, which of the following strategies is MOST critical for the generic manufacturer to implement?
Given the inherent complexities of pressurized delivery systems, which of the following represents the MOST critical challenge in maintaining long-term product performance and patient safety?
Given the inherent complexities of pressurized delivery systems, which of the following represents the MOST critical challenge in maintaining long-term product performance and patient safety?
A researcher is formulating nitroglycerin for sublingual administration to treat acute angina. The objective is to maximize the rate and extent of drug absorption while minimizing pre-systemic metabolism. Which formulation approach would best achieve this goal?
A researcher is formulating nitroglycerin for sublingual administration to treat acute angina. The objective is to maximize the rate and extent of drug absorption while minimizing pre-systemic metabolism. Which formulation approach would best achieve this goal?
A pharmaceutical scientist is tasked with developing an ocular drug delivery system for a novel gene therapy intended to treat retinal degeneration. Considering the unique anatomical and physiological barriers of the eye, which delivery method would MOST effectively target the retinal pigment epithelium (RPE) while minimizing off-target effects and systemic exposure?
A pharmaceutical scientist is tasked with developing an ocular drug delivery system for a novel gene therapy intended to treat retinal degeneration. Considering the unique anatomical and physiological barriers of the eye, which delivery method would MOST effectively target the retinal pigment epithelium (RPE) while minimizing off-target effects and systemic exposure?
In the context of aerosol formulation, consider a scenario where a novel peptide-based drug exhibits significant instability in aqueous solvents. Which strategy would MOST effectively balance drug solubility, chemical stability, and aerosolization performance?
In the context of aerosol formulation, consider a scenario where a novel peptide-based drug exhibits significant instability in aqueous solvents. Which strategy would MOST effectively balance drug solubility, chemical stability, and aerosolization performance?
A researcher aims to improve the transdermal delivery of a large, hydrophilic protein. Which advanced technique would MOST effectively enhance skin permeation while maintaining protein integrity and biological activity?
A researcher aims to improve the transdermal delivery of a large, hydrophilic protein. Which advanced technique would MOST effectively enhance skin permeation while maintaining protein integrity and biological activity?
A pharmaceutical scientist aims to develop a novel topical aerosol formulation for a highly lipophilic drug. Considering the physicochemical properties of the drug and the constraints of pressurized delivery, which propellant system and formulation approach would MOST likely optimize drug delivery into the stratum corneum?
A pharmaceutical scientist aims to develop a novel topical aerosol formulation for a highly lipophilic drug. Considering the physicochemical properties of the drug and the constraints of pressurized delivery, which propellant system and formulation approach would MOST likely optimize drug delivery into the stratum corneum?
In the development of a novel vaginal ring for contraception, what is the MOST critical factor to consider in order to achieve zero-order release kinetics of both a highly lipophilic progestin and a hydrophilic estrogen over a 90-day period?
In the development of a novel vaginal ring for contraception, what is the MOST critical factor to consider in order to achieve zero-order release kinetics of both a highly lipophilic progestin and a hydrophilic estrogen over a 90-day period?
When formulating a metered-dose inhaler (MDI) product containing a potent bronchodilator with a narrow therapeutic index, what strategy would be MOST critical to mitigate the risks associated with potential dose variability?
When formulating a metered-dose inhaler (MDI) product containing a potent bronchodilator with a narrow therapeutic index, what strategy would be MOST critical to mitigate the risks associated with potential dose variability?
Consider the challenge of formulating a thermally labile protein drug into a pressurized aerosol system. Which approach would BEST preserve the protein's structural integrity and biological activity during the manufacturing process and throughout its shelf life?
Consider the challenge of formulating a thermally labile protein drug into a pressurized aerosol system. Which approach would BEST preserve the protein's structural integrity and biological activity during the manufacturing process and throughout its shelf life?
A formulation scientist is tasked with developing a nasal aerosol spray containing a peptide with poor nasal absorption. Which strategy would MOST effectively enhance peptide bioavailability while minimizing mucociliary clearance?
A formulation scientist is tasked with developing a nasal aerosol spray containing a peptide with poor nasal absorption. Which strategy would MOST effectively enhance peptide bioavailability while minimizing mucociliary clearance?
In the design of a pressurized aerosol for delivering a potent anti-inflammatory drug to the deep lung, which factor would have the GREATEST impact on achieving optimal therapeutic efficacy while minimizing systemic side effects?
In the design of a pressurized aerosol for delivering a potent anti-inflammatory drug to the deep lung, which factor would have the GREATEST impact on achieving optimal therapeutic efficacy while minimizing systemic side effects?
Considering the environmental impact and regulatory scrutiny surrounding traditional chlorofluorocarbon (CFC) propellants, which of the following represents the MOST sustainable and technologically viable alternative for pressurized metered-dose inhalers (MDIs)?
Considering the environmental impact and regulatory scrutiny surrounding traditional chlorofluorocarbon (CFC) propellants, which of the following represents the MOST sustainable and technologically viable alternative for pressurized metered-dose inhalers (MDIs)?
A patient reports experiencing inconsistent drug delivery from their topical aerosol medication, despite adhering to the prescribed administration instructions. Which factor is MOST likely contributing to this issue?
A patient reports experiencing inconsistent drug delivery from their topical aerosol medication, despite adhering to the prescribed administration instructions. Which factor is MOST likely contributing to this issue?
In the context of developing a novel aerosol formulation containing a protein therapeutic, what analytical technique would provide the MOST comprehensive assessment of aerosol particle size distribution, protein aggregation, and aerodynamic performance?
In the context of developing a novel aerosol formulation containing a protein therapeutic, what analytical technique would provide the MOST comprehensive assessment of aerosol particle size distribution, protein aggregation, and aerodynamic performance?
Flashcards
Biphasic Solubility
Biphasic Solubility
Low lipid solubility and high water solubility can lead to poor absorption in ophthalmic drugs.
Lachrymal Fluid (Tears)
Lachrymal Fluid (Tears)
Physiological fluid from lachrymal glands, containing lysozyme and electrolytes, with a pH of 7.4.
Function of Lachrymal Fluid
Function of Lachrymal Fluid
Antibacterial action, moisturizing the eye, buffering irritants and washing away irritant substances.
Ophthalmic Preparation Forms
Ophthalmic Preparation Forms
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Oil Ophthalmic Solutions
Oil Ophthalmic Solutions
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Pilocarpine Ophthalmic Solution
Pilocarpine Ophthalmic Solution
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Aqueous Ophthalmic Solutions
Aqueous Ophthalmic Solutions
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Why Use Buffers?
Why Use Buffers?
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Optimal pH Range
Optimal pH Range
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pH stability
pH stability
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Thickening Agents
Thickening Agents
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Examples of Thickening Agents
Examples of Thickening Agents
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Ophthalmic Suspensions
Ophthalmic Suspensions
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Why Prepare Suspensions?
Why Prepare Suspensions?
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Ideal Suspension Properties
Ideal Suspension Properties
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Ophthalmic Ointments
Ophthalmic Ointments
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Vaginal Route
Vaginal Route
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Contraceptive Foams
Contraceptive Foams
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Rectal Route
Rectal Route
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Respiratory Route
Respiratory Route
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Bronchodilators
Bronchodilators
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Nasal Route
Nasal Route
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Nasal Decongestants
Nasal Decongestants
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Nasal Anti-inflammatory Steroids
Nasal Anti-inflammatory Steroids
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Nasal Moisturizers
Nasal Moisturizers
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Antidiuretics
Antidiuretics
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Contact Lens Cleaning Solution
Contact Lens Cleaning Solution
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Pressurized Delivery Systems
Pressurized Delivery Systems
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Advantages of Pressurized Systems
Advantages of Pressurized Systems
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Disadvantages of Pressurized Systems
Disadvantages of Pressurized Systems
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Aerosol Formulation Components
Aerosol Formulation Components
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"Slurry" or "Concentrate"
"Slurry" or "Concentrate"
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Propellant Function
Propellant Function
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Two Phase Aerosol System
Two Phase Aerosol System
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Three Phase Aerosol System
Three Phase Aerosol System
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Solvent
Solvent
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Compressed Gas Propellants
Compressed Gas Propellants
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Carbon Dioxide Propellant
Carbon Dioxide Propellant
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Nitrous Oxide Propellant
Nitrous Oxide Propellant
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Surfactants
Surfactants
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Anionic Surfactants
Anionic Surfactants
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Study Notes
Ophthalmic Preparations
- Ophthalmic preparations are sterile pharmaceutical products, free from foreign particles and specifically prepared for instillation in the eye
- Ophthalmic preparations are used as local anesthetics to relieve pain
- They are also used diagnostically as Mydriatics, to dilate the eye pupil and ease examination
- Miotics are also used diagnostically to reduce intra-ocular pressure if associated with glaucoma
- Anti-inflammatory and anti-infective properties reduce inflammation to treat microbial or viral infections
Eye Anatomy
- The cornea is the most essential layer that controls the drugs that enter eye while the conjunctiva is generally permeable to most drugs
- The conjunctiva is composed of mucous glands to keep the eye moist
- The conjunctiva contains rich blood vessels that dilate and cause redness if irritated by foreign particles or microbial infection
- The cornea is the main membrane controlling the permeation of drugs into the eye
- The cornea is non-vascular, transparent, and rich with sensory nerves for the sensation of pain and pressure
Cornea Layers
- The cornea is comprised of three layers:
- Epithelium is a lipophilic layer composed of lipoprotein
- Stroma is mainly aqueous in nature and hydrophilic
- Endothelium layer is a lipoprotein layer that is lipophilic
- The cornea is composed of lipid/water/lipid layers
- For high absorption and penetration of drugs through the cornea, there must be biphasic solubility in water and lipid
- Dexamethasone is an anti-inflammatory agent that, if formulated as dexamethasone-acetate (salt), will be highly absorbed given the biphasic nature
- Dexamethasone-sodium phosphate has low lipid solubility and high water solubility, leading to poor absorption, the biphasic solubility is therefore important
- Most drugs in ophthalmic preparations are weak basic drugs of acidic salts such as Pilocarpine-Hcl or Atropin-So4
Lachrymal Fluid
- This fluid/tears is a physiological secretion of lachrymal glands located at the corners of the upper lid
- Excess fluid or tears usually drains into the nasal cavity
- Lachrymal fluid has a pH of 7.4 and contains lysozyme (electrolytes such as sodium chloride and sodium bicarbonate) as well as proteins
- Lysozyme has antibacterial properties to protect the eye against microbial contamination
- Secretion helps to protect the eye and keep it moist, while dilution washes off any irritating substances to neutralize any irritant effect
- The eye can hold a maximum volume of 30 μl (microliters) and any excess volume will be drained
Ophthalmic Preparation Formulations
- Drugs are formulated as ophthalmic preparations in the form of solutions, suspensions, ointments and ocuserts
- Types of ophthalmic solutions- oily and aqueous
Oily Ophthalmic Solution
- A sterile solution has drugs dissolved in oil vehicles (usually castor oil)
- These solutions do not contain preservatives, buffers or thinking agents, which is due to the nature of oily solutions not supporting microorganism growth
- These solutions also maintain a constant PH and are highly viscous
- Pilocarpine in castor oil is an example (used to treat glaucoma), and is viscous, remain in contact with the conjunctiva for a long period to maximize absorption of medications
- The solution will enhance the drugs duration of action, but it may also interfere with eye vision, potentially causing blurry vision
Aqueous Ophthalmic Solution
- Includes a sterile solution of drugs and other suitable ingredients dissolved in aqueous vehicles for instillation into the eye
- Most drugs are prepared as aqueous ophthalmic solutions
- During preparation a few steps must kept- Sterility and preservation, Tonicity isotonic with lachrymal fluid, Buffering, Thickening agents can be added to aqueous solutions
- Sterilization can be achieved with autoclaving or filtration
- To prevent the growth of microorganisms, an antimicrobial agent/preservative is added to ophthalmic solutions
Preservatives
- A preservative should be non-irritant, non-toxic, inert, effective against a wide range of microorganisms (especially Pseudomonas aeruginosa), compatible with other ingredients, soluble and stable in the buffer, withstand high temperatures applied during autoclaving
- Preservatives commonly used: phenyl mercuric nitrate, benzalkonium chloride and chlorobutanol
Tonicity
- An isotonic/iso-osmotic solution has equal osmotic pressure to that of body fluids, including blood and lachrymal fluid
- Solutions with lower pressure than body fluids are hypotonic, while higher ones are hypertonic
- Two methods to calculate isotonicity for ophthalmic solutions: sodium chloride equivalent method and the freezing point depression method
Maintaining Solubility
- Buffers having low pH (4-5) are suitable for the solubility of basic drugs such as local anesthetics (Procaine, Dibucaine), Pilocarpine Hcl and Atropine So4
- Boric acid provides a pH of (4-5) by dissolving 1.9 g of boric acid in 100 ml of water
- High pH buffers (6-8) are suitable for acidic as well as neutral drugs such as Sulphacetamide sodium, Flurbiprofine sodium or Prednisolone acetate
- Phosphate buffer provides a pH range of (6-8), prepared by mixing sod dihydrogen phosphate and disodium hydrogen phosphate to the production desired PH
Maintaining Stability
- Chosen pH or buffer should provide stable environment for the drug
- Drugs such as Pilocarpine or Procaine are degraded at low and high pH's with a PH maximum stability should be chosen to avoid the degradation
Thickening Agents
- Used in some ophthalmic solutions to maintain viscosity, hold the drug in contact with the eye tissues, enhance its absorption and effectiveness
- Examples include cellulose derivatives (methyl cellulose, hydroxyl propyl cellulose, hydroyethyl cellulose) polyvinyl alcohol and polyvinylpyrrolidone
Ophthalmic Suspensions
- These suspensions are a sterile preparation in which insoluble drugs products aresuspended or dispensed in aqueous vehicle, also include additives such as suspending agents, tonicity adjusting substances, buffering agents and preservatives
Why Ophthalmic Solutions are Prepared
- Necessary if drugs are unstable and hydrolysable and if prolonged action is required
- Ideal properties should be sterile, well preserved, dispersed easily, give a uniform dose, have good distribution properties, and isotonic using suitable buffer to minimize the irritation
- Examples include Tetracycline Ophthalmic, Oxytetracycline and hydrocortisone, Sulphacetamide and prednisolone
Ophthalmic Ointments
- Ophthalmic ointments are sterile semisolid preparations containing drugs incorporated into the ointment bases
- After applying the ointment, a ribbon is gently placed on the lower eye lid
- The preparation involves melting the ointment base and adding a fine powdered drug, then triturating until homogenization
- Dry heat sterilization is then deployed in the mixture by placing sterilizing equipment (oven) for two hours at 170°C
- Then the sterilized ointment is filled into a collapsible plastic tube that was previously sterilized, before closing with screw caps made of aluminum or plastic
Ointment Bases
- Hydrocarbon bases consist of yellow soft paraffin, liquid paraffin and anhydrous lanolin
- Ointment base properties should be inert, non-irritant, non-toxic properties, compatible with incorporated drugs.
- It releases the drug after melting at body temperature and is thermo-stable at a high temperature
Ointment Advantages
- The viscosity of the base and long contact with the tissues lead to slower drug release and prolonged action of the drug
- Disadvantages includes hazy vision from an oily film over the conjunctiva Examples include Atropine sulphate, Chloramphenicol and Neomycin
Ocuserts (Ophthalmic Inserts)
- It is a newly developed device for inserting a drug to the lower eye lid
- The device is designed for a consistent and continuous drug release that lasts a long time
- Ocuserts are transparent, sterile oval in shape, composed of reservoir containing medicaments surrounded in each side by polymeric membrane
- A polymeric membrane controls how fast the drug is released from the reservoirs and is composed of very thin microscopic holes
- Pilocarpine is an example, and such ocuserts release the drug at a rate of 20-40-80 ug/hr for 7 days
Ocuserts - Advantages
- Easy to use over long periods of time.
- Provide continuous drug release and used for chronic diseases such as glaucoma
Ophthalmic Drugs
-
Control eye diseases, such as:
- Antiseptics: silver and ammonium nitrate
- Antibiotics: Gentamicin, Neomicin, Chlormphenicol, Tetracyclin and Sulphcetamide
- Anti-inflammatory: Hydrocortisone, prednisolone and Dexamethasone
- Local anesthetics: Procaine, Tetracaine, Dibucaine and proparacain
- Miotics: Pilocarpine
-
Other drugs
- Myrdrotics: Atropine, Scopolamine
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Diagnostics: Fluorescin
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Anti adrenergic: Timolol and Betaxolo
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Anti allergic: Sodium chromoglycate
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Vasoconstriction: Naphazolin, Phenyleherine and Tetrahydrozoline
Pharmaceutical Aerosols
- Definition: A suspension of small solid particles or droplets suspended in a gas or vapor
- Pharmaceutical aerosols are usually unstable
- Products expel contents from a container, thanks to the pressure of compressed/liquified gas
Aerosol Anatomy
- Actuator
- Valve Stem
- Canister
- Dip-tube
- Aerosol
- Valve
- Compressed gas or propellant vapor
- Liquefied Propellant or Solvent
Pharmaceutical Aerosol - Topical Uses
- Local anesthetics (e.g. Benzocaine)
- Wound washing
- Rubiferants (e.g. Methylsalicylate)
- Proprietary burn applications
- Antibacterials (e.g. Neomycin)
- Antifungal sprays (Miconazole)
- Anti-inflammatory steroids (e.g. Dexamethasone)
Pharmaceutical Aerosol - Oral and Lingual Uses
- Antacids (e.g. Aluminum and magnesium silicate)
- Local anesthetics (e.g. Lidocaine)
- Antiseptics (e.g. Chloroseptic)
- Anti-anginals (e.g. Nitroglycerin)
Pharmaceutical Aerosol - Vaginal Uses
- Contraceptive Foams (e.g. Nonoxyenol-9) - provides access to hard to reach sites, expands to fill the available space, and provide complete surface coverage
Pharmaceutical Aerosol - Rectal Uses
- Local anesthetics (e.g. Pramoxine)
- Anti-inflammatory steroids (e.g. Hydrocortisone)
Pharmaceutical Aerosol - Respiratory Uses
- Bronchodilators (e.g. Albuterol)
- Anti-inflammatory steroids (e.g. Beclomethasone)
- Antiallergics (e.g. Cromolyn sodium)
- Antivirals (e.g. Ribavirin)
- Smoking cessation (e.g. Nicotine)
- Migraine (e.g. Ergotamine tartrate)
Pharmaceutical Aerosol - Nasal Uses
- Decongestants (e.g. Phenylephrine)
- Anti-inflammatory steroids (e.g. Beclomethasone)
- Antiallergics (e.g. Cromolyn sodium)
- Moisturizers (e.g. Normal saline)
- Systemic access
- Antidiuretics (Desmopressin)
- Antismoking (Nicotine)
Pharmaceutical Aerosol - Ocular Uses
- includes Contact lens cleaning solutions
Pressurized Delivery System Advantages
- Easy to use and convenient
- Remaining product is not contaminated during use
- Aerosol can be filled aseptically, tamper-proof capabilities
- Protects unstable drugs from light, oxygen and water
- The target site need not be touched, which is particularly useful for burns
Pressurized Delivery System Disadvantages
- Can be expensive
- Performance may deteriorate over time
- There is a limited safety hazard with flammability
- Pressurized formulations
- Inadvertent inhalation
- Sometimes is prone to incorrect use
- It is growing trend of topical and nasal sprays converting to water based pump sprays
Aerosol Formulations
- Active Ingredient (drug)
- Solvents/cosolvens
- Propellant system
- Surfactants
- Miscellaneous
- Antioxidants
- Preservatives
- Flavouring agents
- Buffers
- Perfumes
- The drug and less volatile components are collectively termed the "slurry" or "concentrate"
Pressurized Aerosol Formulation
- Propellants provide the driving force to expel product from its container
- Provide a dispersion medium as well
Types of Pressurized Formulations
- Two Phase
- Dry Mist
- Three Phase
- Wet Mist
- Foam
Propellants
- Hydrocarbon Propellants (most common)
- Advantages- Inexpensive, Minimal Ozone Depletion, Excellent Solvents
- Disadvantages- Flammable, Aftertaste, Toxicity following Inhalation, Low Liquid Density
Hydrocarbon Properties
- Property: n-Butane, Isobutane, Propane
- Boiling point (°C): -0.5, -11.7, -42.1
- Vapor pressure at 25°C (Pounds/square inch): 31,45,125 -Liquid density at 25°C (g/ml): 0.58, 0.56, 0.51
Chlorofluorocarbons
- (Used only in Inhalation Aerosols)
- Advantages include low inhalation toxicity, high purity and high chemical stability
- Cons include high cost
Hydrofluoroalkanes
- HFA
- Advantages: Low inhalation toxicity, high chemical stability, high purity, not ozone depleting -Disadvantages: Poor solvents, high cost
Compressed Gas Propellants
- Advantages include minimal inhalation toxicity, high chemical stability, high purity, inexpensive and non-hazardous to Ozone -Disadvantages include the use of a nonvolatile co-solvent, course droplet sprays -Pressure falls during use
Types of Surfactants
- Anionic, e.g. oleic acid Cationic, e.g. cetylpyridinium chloride, Zwitterionic, e.g. phosphatidylcholine
- Nonionic e.g. sorbitan trioleate
Function of Surfactants
- Valve lubrication
- Aid homogeneous dispersion of solid particles in solvent and propellant systems
- Maintain stability of "foaming" aerosols -Emulsify propellant and aqueous phase in emulsion aerosols, Enhance dissolution of medicament in propellant or solvent system
- Functions of surfactants include valve lubrication, aid of homogenous dispersion of solid particles in solvent and propellant systems, maintains stability of foaming aerosols, also emulsifies propellant and aqueous phase in emulsion aerosols, enhances dissolution of medicament in propellant or solvent system
Formulation of Drugs
- Possible that Drugs will dissolve in the propellant systems- Small particles can be achieved after complete evaporation, simplified process -Drug must be soluble with chemical degradation may occur faster
Formulation of Suspensions
- Drugs can be delivered if insoluble
- Higher doses may be achieved
- Constant agitation is required with physical instability
- Drug particle size depends on the intended use of the product <5 micrometers is for inhalation
- 10 - 40 micrometers is for topical sprays
Cosolvent
- They are used to dissolve medicament in propellant/solvent system
- Water content to increase droplet size and wetness
- Lower pressure is used to promote miscibility between solvents
Example Composition of Aerosols
- Albuterol is included for inhalation, Miconazole for topical sprays, Nonoxenol-9 for Vaginal Foam
Types of Pressurized Aerosol
- Fine/course sprays- Anti fungal/Antiseptic
- Stable Foams
Packaging - Components Include Plastic Coated Glass
- Allows visibility of compounds; the material is compatible with most formulations
- Absorbs "neckshock" during crimping and provides barrier to broken glass but has an aesthetic visual finish, for dissolving drug
- Aluminum is both light weight and seamless, opaque
Types of Valves
_ Continuous
- A definite volume is released in small increments. Used for topical and inhalation
Drug Delivery Systems:
- Pulmonary Delivery/ Filling in both hot and cold temperatures
- Testing for any contamination
- Accuracy and reproducibility of dosage when using metered valves. The method used must be correct to ensure the integrity
Filling Problems:
- Escape of propellant due to distorted filling
- Wrong filling of nozzles
- Distorted ferrule doming and crimping
Quality Control Tests:
- Testing and inspection for- Drug contamination through different stages, propellant leakage, product rate and tests for inhalation as well
Aerosols:
- Composed of space sprays, surface coating, aerated sprays
Aerosol - Advantages
- Includes the ability to control the particle size with decreased irritation. Also topical medication to be applied to the skin
- Local treatment for diagnosing pulmonary infection or other systematic infections; rapidly reduced side effects with rapid release
The Lymphatics carries O2 around the Respiratory System. Factors such as particle and kinetic action will affect the deposition w/ lung and tissue deposition
Factors that affect Desposition
- Method of Inhalation
- Mode of application
- Aerosal diameter influences that rate of deposition. Ideal is 5 micrometers Packaging and the storage that include labels and warnings for possible side -effects
3 Common Devices to help Aerosol usage
- metered dose inhaler
- nebulizer
- dry powdered inhaler
Drug Delivery Spray
: solutions may or may not need to be directly used on the skin
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