Define pulmonary Route administration. Expla in detail abt & Formulf of meter dose inhales (IPA).

Pulmonary route administration is the delivery of drugs or therapeutic agents directly into
the respiratory system through inhalation, allowing for rapid absorption into the
bloodstream and localized treatment of respiratory conditions.

1. Medication Formulation:

• Solution vs. Suspension: Medications in MDIs can be formulated either as

solutions or suspensions in a liquefied propellant.
• Solution Formulation: In solution MDIs, the drug is completely dissolved
in the formulation. This results in a homogeneous mixture, and patients
do not need to shake the inhaler before use. There are no concerns
regarding the sampling homogeneity, and the aerosol produced tends
to be finer and more uniform.
• Suspension Formulation: In suspension MDIs, the drug is not fully
soluble in the formulation, resulting in small solid particles suspended
in the propellant. This may require patients to shake the inhaler before
use to ensure an even distribution of the drug.
• Drug Solubility: When formulating a solution MDI, it's crucial to consider the
solubility of the drug in the propellant. Many drugs are not readily soluble in
certain propellants like hydrofluoroalkane (HFA), which can limit the amount
of drug that can be effectively dosed.
• Surfactants and Complexation Aids: In the past, surfactants or complexation
aids were used in chlorofluorocarbon (CFC) MDIs to increase drug solubility.
However, these conventional excipients are often insoluble in HFA systems,
making it necessary to find alternative approaches to enhance solubility in
HFA-based MDIs.
• Particle Size: The method for preparing drug particles depends on the
chemical stability of the drug. For example, protein-based drugs are heat-
labile and require special handling to preserve their three-dimensional
conformation and biological activity. Spray-drying with suitable agents (e.g.,
sodium carboxymethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone) is
commonly employed for protein drugs.

2. Basic Requirements for MDI Formulation:

• Containers: The MDI typically consists of a canister that holds the

formulation. These canisters are typically made of metal (e.g., aluminum) and
are designed to withstand pressure. They are sealed to prevent leakage and
maintain product integrity.
 • Propellants: Propellants are the gases used to expel the medication from the
canister. Common propellants include hydrofluoroalkanes (HFAs), which are
considered environmentally safer alternatives to chlorofluorocarbons (CFCs).
The choice of propellant can affect the solubility of the drug and the overall
performance of the MDI.
• Metering Valve: The metering valve is a critical component that precisely
measures and delivers a specific dose of medication with each actuation of the
inhaler. The valve must be designed for accuracy and consistency in dosing.

3. Filling the MDI Canister:

• Cold Filling: In cold filling, the active compound, excipients, and propellant
are chilled to around -60°C. The canister is filled at this low temperature, and
additional propellant is added at the same temperature. The valve is then
sealed onto the canister. Cold filling is used to maintain stability and avoid
changes in the formulation due to temperature variations.
• Pressure Filling: In pressure filling, a drug/propellant concentrate is produced
and filled at or near room temperature and pressure, typically slightly chilled
to below 20°C. The valve is crimped onto the canister, and additional
propellant is added at elevated pressure through the valve in a process known
as gassing. Pressure filling is a commonly employed method for inhalation
aerosols.
define and classify lyposomes. Explain different methods for prepataion of lyposomes

Liposomes are artificial vesicles or tiny spherical structures composed of one or more lipid
bilayers, which are similar in structure to the phospholipid bilayers that make up cell
membranes. These lipid bilayers enclose an aqueous (water-based) interior, creating a
compartment that can encapsulate various substances such as drugs, nutrients, or other
compounds.

Liposomes in NDDS (Nanoparticle Drug Delivery Systems) can be classified based on

various factors. Here's a point-form classification:

1. Based on Composition:
• Unilamellar Liposomes: Single lipid bilayer.
• Multilamellar Liposomes: Multiple concentric lipid bilayers.
• Cationic Liposomes: Contain positively charged lipids for nucleic acid
delivery.
• PEGylated Liposomes: Surface-modified with PEG for extended
circulation time.
2. Based on Size:
• Small Unilamellar Vesicles (SUVs): Diameter typically below 100 nm.
• Large Unilamellar Vesicles (LUVs): Diameter typically 100-1000 nm.
• Giant Unilamellar Vesicles (GUVs): Very large vesicles, often used for
research.
3. Based on Charge:
• Anionic Liposomes: Negative charge on the surface.
• Cationic Liposomes: Positive charge on the surface.
• Neutral Liposomes: No net charge on the surface.
 4. Based on Preparation Method:
• Extrusion Liposomes: Prepared by forcing lipid dispersion through
small pores.
• Sonicated Liposomes: Formed by ultrasonic energy.
• Reverse-Phase Evaporation Liposomes: Created using organic
solvents and evaporation.

Mop.

I. Passive Loading Techniques:

1. Mechanical Dispersion: (a) Lipid Hydration Method:

• This method involves preparing multilamellar vesicles (MLVs) by
forming a thin lipid film, hydrating it with an aqueous buffer above the
gel-liquid crystalline transition temperature of the lipid.
• Compounds to be encapsulated are added to either the aqueous buffer
or organic solvent containing lipids.
• Disadvantages include low internal volume, low encapsulation
efficiency, and varying vesicle sizes. Encapsulation efficiency can be
improved by hydrating lipids in immiscible organic solvents like
petroleum ether or diethyl ether.
• MLVs can be formed by emulsification through sonication or by
nitrogen removal.
(b) Micro Emulsification:
• Used for preparing small lipid vesicles in large quantities.
• Achieved by micro-emulsifying lipid compositions using high-pressure
homogenizers.
• High-speed rotations (20 to 200) generate shear stress.
(c) Sonication:
• Involves sonication of MLVs using a bath-type sonicator or probe
sonicator.
• Drawbacks include low internal volume, degradation of phospholipids,
exclusion of large molecules, potential metal contamination, and
coexistence of MLVs with small unilamellar vesicles (SUVs).
(d) French Pressure Cell Method:
• Involves extrusion of MLVs through a small orifice at high pressure
(20,000 psi) at low temperature (4°C).
• Advantages include simplicity, rapidity, reproducibility, and gentle
handling of unstable materials.
• Resulting liposomes are larger than sonicated SUVs, but difficulties may
arise in maintaining the required temperature and limited working
volume.
(e) Membrane Extrusion:
 • Liposomes are passed through a polymer filter with a web-like
structure, providing a narrow size distribution and selected average size
less than about 0.4 microns.
(f) Dried Reconstituted Vesicles:
• Preformed liposomes are added to an aqueous solution containing the
drug or mixed with a lyophilized dehydration mixture.
(g) Freeze-Thaw Method:
• Small unilamellar vesicles (SUVs) are rapidly frozen, followed by slow
thawing, leading to the formation of ultra-small vesicles (ULVs).
• Fusion of SUVs during freezing and thawing results in ULV formation.
• Entrapment efficiencies of 20-30% can be achieved using this method.
2. Solvent Dispersion: (a) Ethanol Injection Method:
• Lipid solution in ethanol is rapidly injected into excess buffer to form
MLVs.
• Drawbacks include heterogeneous size distribution and difficulty in
removing all ethanol, which may form an azeotrope with water.
(b) Ether Infusion Method:
• Lipids dissolved in diethyl ether or ether-methanol mixture are slowly
injected into an aqueous solution of the drug.
• Liposomes are reformed by removing ether under vacuum, but
drawbacks include exposure to organic solvents and high temperatures,
leading to size variations.
(c) Double Emulsification:
• Involves primary emulsion preparation by dissolving the drug in an
aqueous phase, followed by emulsification in an organic solvent to
make a primary w/o emulsion.
• Further mixing with an emulsifier-containing aqueous solution results
in a w/o/w double emulsion.
(d) Reverse-Phase Evaporation:
• Lipid mixture is dissolved in an organic phase, and the solvent is
removed under reduced pressure.
• Lipids are re-dissolved in the organic phase, and the aqueous phase
with the drug is added.
• Sonication is performed until a clear one-phase dispersion is achieved.
• Organic solvent removal leads to the formation of reverse-phase
evaporation vesicles.
3. Detergent Removal:
• Detergent dialysis method involves solubilizing lipids with detergents at
their critical micellar concentrations.
• Detergent is removed by dialysis, leading to the formation of large
unilamellar vesicles (LUVs).
• Advantages include reproducibility and homogeneous vesicle
populations, but detergent contaminants may be retained.
II. Active Loading Techniques:

(a) Proliposome:

• Lipid and drug are coated onto a soluble carrier to form free-flowing granular
material.
• On hydration, an isotonic liposomal suspension is formed.
• Suitable for large-scale production of liposomes containing lipophilic drugs.

(b) Lyophilization (Freeze Drying):

• Used to dry thermolabile products that could be damaged by heat-drying.

• Addresses long-term stability issues with liposomes but may lead to leakage
of entrapped materials during the process and upon reconstitution.

Write in detail on non harmonal / copper IUDS with moa

Introduction:

• Intrauterine Device (IUD) is a small device placed in the uterus through the
cervix to prevent pregnancy.
• IUDs are highly effective, with a birth control success rate of 99.2-99.9%.
• However, they do not provide protection against sexually transmitted
diseases, including HIV/AIDS.

Mechanism of Action:

Copper intrauterine devices (IUDs) are non-hormonal contraceptive devices. They

work by utilizing the following mechanisms:

1. Copper Ions Release: Copper IUDs are typically made with a copper wire or
sleeve. They release copper ions into the uterine environment.
2. Sperm Immobilization: Copper ions are toxic to sperm, impairing their
motility and making it difficult for them to reach and fertilize the egg.
3. Prevention of Fertilization: Copper also changes the biochemical
environment within the uterus, making it less conducive for fertilization to
occur.
4. Prevention of Implantation: Copper-induced changes in the uterine lining
make it less suitable for a fertilized egg to implant, thus preventing pregnancy.

Applications:
 1. Contraception: The primary application of copper IUDs is as a highly effective
method of contraception. They are inserted by a healthcare provider and can
provide protection against pregnancy for up to 10 years, depending on the
specific brand and model.
2. Emergency Contraception: Copper IUDs can also be used as emergency
contraception when inserted within a certain timeframe after unprotected
intercourse (typically within 5 days).

Advantages:

1. Highly Effective: Copper IUDs are one of the most effective forms of
contraception, with a failure rate of less than 1%.
2. Long-Lasting: Depending on the model, they can provide protection for 3 to
10 years, reducing the need for regular contraceptive maintenance.
3. No Hormones: They do not contain hormones, making them a suitable
option for women who cannot or prefer not to use hormonal contraceptives.
4. Quick Reversibility: Once removed, fertility usually returns to normal, making
them suitable for those planning to conceive in the future.
5. Non-Interference with Sexual Activity: Unlike other contraceptive methods,
copper IUDs do not require any action or planning before sexual activity.
6. Non-Systemic: Because copper IUDs release copper locally in the uterus,
there are no systemic side effects.

Disadvantages:

1. Heavier and Painful Periods: Copper IUDs are associated with an increase in
menstrual bleeding and cramping, which can be uncomfortable for some
women.
2. Initial Discomfort: Some women may experience discomfort or pain during
the insertion process.
3. Risk of Expulsion or Perforation: There is a small risk of the IUD being
expelled from the uterus or, in rare cases, perforating the uterine wall during
insertion.
4. Infection Risk: While the IUD itself does not cause infections, it can slightly
increase the risk of pelvic inflammatory disease (PID) if an individual is already
at risk.
5. No Protection Against Sexually Transmitted Infections (STIs): Copper IUDs
do not provide protection against STIs, so additional methods (e.g., condoms)
are recommended for those at risk.
6. Cost: The upfront cost of getting a copper IUD and the associated medical
procedures can be relatively high.

Discribe hormonal IUD drug delivery system

Mechanism of Action:

Hormonal intrauterine devices (IUDs) use synthetic hormones, typically

levonorgestrel, to prevent pregnancy. Here's how they work:

• Progestin Release: Hormonal IUDs release a controlled amount of synthetic

progestin (levonorgestrel) into the uterus.
• Thickening Cervical Mucus: The progestin thickens cervical mucus, making it
difficult for sperm to pass through the cervix.
• Inhibiting Sperm Function: Progestin also impairs sperm function, reducing
their ability to reach and fertilize the egg.
• Uterine Lining Changes: The hormones alter the uterine lining, making it less
suitable for implantation, which reduces the likelihood of pregnancy even if
fertilization occurs.

Applications:

1. Contraception: The primary use of hormonal IUDs is as a highly effective

contraceptive method. Depending on the specific device, they provide
protection for 3 to 5 years.
2. Menstrual Regulation: Hormonal IUDs are often prescribed to address heavy
menstrual bleeding (menorrhagia) and to alleviate menstrual pain. Users may
experience lighter periods with less pain.

Advantages:

1. Highly Effective: Hormonal IUDs have a very low failure rate, making them
one of the most effective forms of contraception, with a typical use failure rate
of less than 1%.
2. Long-Lasting: Depending on the type, they offer protection for several years,
reducing the need for frequent contraceptive maintenance.
3. Lighter and Less Painful Periods: Many users report reduced menstrual
bleeding and cramping, which makes them an attractive option for managing
heavy and painful periods.
4. Quick Reversibility: Fertility usually returns promptly after removal, making
them suitable for individuals planning to conceive in the future.
5. Reduced Risk of Pelvic Inflammatory Disease (PID): The hormonal IUD can
create a barrier to pathogens by thickening cervical mucus, which may provide
some protection against PID.
6. Non-Interference with Sexual Activity: No action or planning is needed
before sexual activity, which can be a significant advantage for couples.

Disadvantages:
 1. Initial Discomfort: Insertion can cause discomfort or pain in some women.
2. Risk of Expulsion or Perforation: There is a small risk of the IUD being
expelled from the uterus or, in rare cases, perforating the uterine wall during
insertion.
3. Hormone-Related Side Effects: Some users may experience hormonal side
effects like changes in mood, acne, or breast tenderness.
4. No Protection Against STIs: Hormonal IUDs do not protect against sexually
transmitted infections (STIs), so additional precautions are needed for
individuals at risk.
5. Cost: The upfront cost of getting a hormonal IUD and the associated medical
procedures can be relatively high.
6. Menstrual Irregularities: While many users experience lighter periods, some
may also experience irregular bleeding or spotting, especially during the initial
months of use.
7. Preexisting Conditions: Hormonal IUDs may not be suitable for individuals
with certain medical conditions, such as liver disease or certain types of breast
cancer.
8. Need for Prescription and Insertion: Hormonal IUDs require a healthcare
provider's prescription and professional insertion, which may not be as readily
accessible in some regions.

Short note on neosomes

Introduction:

• Niosomes are a novel drug delivery system.

• They are vesicles with a bilayer of non-ionic surfactants.
• Similar to liposomes in structure but made of non-ionic surfactants.

Structure:

• Niosomes have a bilayer structure with hydrophilic ends on the outside and
inside.
• The bilayer encapsulates hydrophobic drugs, while the vesicle interior holds
hydrophilic drugs.
• Typically stabilized by cholesterol and a small amount of anionic surfactant.

Types:

1. Small Unilamellar Vesicles (SUVs): Prepared by sonication or French Press, with

a size of 0.025-0.05μm.
 2. Multi-Lamellar Vesicles (MLVs): Comprising multiple bilayers, prepared by
hand-shaking, with a size of 0.5-10μm.
3. Large Unilamellar Vesicles (LUVs): Prepared by injecting lipids into an aqueous
buffer, with a size >0.10μm.

Methods of Preparation:

1. Ether Injection Method: Dissolving the surfactant/cholesterol mixture in

diethyl ether and injecting it into an aqueous phase at 60°C.
2. Hand Shaking (Film) Method: Forming a surfactant/lipid film and hydrating it
with a drug solution.
3. Sonication: Adding an aqueous phase to the surfactant/cholesterol mixture
and probe-sonicating to yield SUVs.
4. Extrusion Method: Preparing a mixture of cholesterol and diacetyl phosphate,
forming a thin film, and hydrating it with an aqueous drug solution, followed
by extrusion.
5. Microfluidization Method: Using ultra-high velocity interaction of drug and
surfactant streams in microchannels.
6. Reverse Phase Evaporation: Forming an o/w emulsion from an aqueous drug
solution and evaporating the organic solvent.

Evaluation:

1. Size, Shape, and Morphology: Determined using freeze fracture electron

microscopy and photon correlation spectroscopy.
2. Entrapment Efficiency: Measured by separating untrapped drug using
methods like dialysis or using markers like Carboxyfluorescein.
3. Osmotic Activity: Studied by observing changes in vesicle size in hypertonic or
hypotonic solutions.
4. Vesicle Surface Charge: Characterized in terms of voltage at the particle
surface and zeta potential.

Applications:

1. Targeting of Bioactive Agents to Reticulo-Endothelial System (RES) or other

organs.
2. Neoplasia: Enhancing the efficacy of anti-tumor drugs with reduced side
effects.
3. Leishmaniasis: Targeting parasites residing in organs.
4. Delivery of Peptide Drugs: Improving peptide stability.
5. Immunological Application: Acting as potent adjuvants in immune responses.
6. Niosomes as Carriers for Haemoglobin: Using them as carriers for oxygen.
7. Transdermal Delivery of Drugs: Increasing drug penetration through the skin.
 8. Sustained Release: Offering controlled release of drugs.
9. Localized Drug Action: Keeping drugs localized at the administration site,
reducing systemic effects.

Advantages:

• Water-based vehicle for better patient compliance.

• Accommodate drugs with varied solubility.
• Controllable formulation characteristics.
• Controlled drug release.
• Osmotically active and stable.
• Biodegradable, biocompatible, and non-immunogenic surfactants.
• Improve drug bioavailability and skin penetration.
• Suitable for oral, parenteral, and topical administration.

Disadvantages:

• Low solubility.
• Short half-life.
• High production cost.
• Potential for aggregation, fusion, leakage of entrapped drugs, and physical
instability.

Explain in detail method to overcome barriers in ocular drug delivery system

here are the methods to overcome barriers in ocular drug delivery explained in
points:

1. Intravitreal Injections:
• Directly deliver drugs into the vitreous humor, bypassing the cornea
and scleral blood vessels.
• Allows for various drug formulations, including solutions, suspensions,
and depots.
• Elimination of drugs can occur through the retina or the anterior
chamber, following a first-order rate of decline.
• The elimination rate correlates with the drug's molecular weight, with
larger molecules having longer half-lives.
• Associated with adverse effects like retinal detachment, cataracts,
hyperemia, and endophthalmitis.
• Sustained release systems can reduce administration frequency and
improve patient compliance.
2. Subconjunctival Injections:
 • Administer drugs beneath the conjunctival membrane, avoiding the
cornea and conjunctiva, and providing direct access to the sclera.
• Less invasive with fewer side effects compared to intravitreal injections.
• Effective for delivering hydrophilic drugs by bypassing rate-limiting
barriers.
• Suitable for depot-forming formulations and the delivery of
macromolecular drugs like Avastin and insulin.
3. Retrobulbar and Peribulbar Route:
• Retrobulbar: Injection placed through the eyelid and orbital fascia to
deliver drugs to the back of the eyeball.
• Used for antibiotics, corticosteroids, and anesthetic agents.
• Delicate procedure with potential optic nerve damage, requiring
expertise and proper equipment.
• Peribulbar: Injections above and/or below the eye globe, often used for
anesthesia in cataract surgery.
• Safer than retrobulbar injections but may still lead to elevated
intraocular pressure in some cases.
4. Sub-Tenon Injections:
• Administered into the cavity between Tenon's capsule and the sclera
using a blunt cannula.
• Does not require deep sedation, making it safer for anesthesia delivery.
• Effective for steroids in treating conditions like uveitis, macular edema,
and non-necrotizing scleritis.
5. Intracameral Injections:
• Similar to intravitreal injections but delivers drugs to the anterior
chamber.
• Limited access to the posterior segment.
• Commonly used for anterior segment procedures like cataract surgery.
• Effective in reducing post-operative inflammation and cost-effective for
delivering antibiotics compared to topical antibiotics and antifungal
agents.

Role of Monoclonal Antibodies in NDDS:

1. Targeted Drug Delivery:
• Engineered to recognize and bind to specific biomarkers.
• Precisely delivers drugs to the desired site of action.
• Valuable in cancer treatment for sparing healthy cells.
2. Enhanced Drug Bioavailability:
• Extends drug circulation time in the bloodstream.
 • Increases drug half-life by protecting it from degradation.
• Reduces the need for frequent dosing.
3. Reduced Side Effects:
• Minimizes exposure of healthy tissues to the therapeutic agent.
• Lowers the risk of side effects and adverse reactions.
4. Immunomodulation:
• Modulates the immune system's responses.
• Used in autoimmune diseases to inhibit immune responses.
• Stimulates immune responses in cancer therapy.
5. Therapeutic Applications:
• Developed for a wide range of diseases, including cancer, autoimmune
diseases, and infectious diseases.
• Designed to block specific signaling pathways or bind to disease-
related receptors.
6. Personalized Medicine:
• Tailored to individual patients based on their unique disease
characteristics.
• Enables more effective and safer treatments.
7. Diagnostic Applications:
• Used in immunoassays to detect specific biomarkers and disease-
related proteins.
8. Combination Therapies:
• Combined with traditional small molecule drugs for enhanced efficacy.
• Common in cancer therapy with antibody-drug conjugates (ADCs).
9. Drug-Drug Interactions:
• Considered to address potential interactions affecting
pharmacokinetics and pharmacodynamics when using monoclonal
antibodies in combination with other drugs.