Inhaled formulations

Inhaled formulations Nasal formulations:<ul><li>Local treatment:<ul><li>Cold and flu</li><li>Allergies</li></ul></li><li>Systemic treatment:</li><li>Smoking cessation<ul><li>Diabetes</li><li>Migraine</li><li>Pain management</li><li>Vaccination</li><li>nasal cavity is lined up with epithelial cells which can take up the drug and distribute through blood which can provide systemic affects</li></ul></li><li>Formulations<ul><li>Liquid</li><li>Gel</li><li>Cream</li><li>Ointment</li></ul></li><li>Nasal formulation considerations:<ul><li>Solubility - needs to dissolve in 25-200 microliters volume</li><li>More lipophilic drugs are more readily absorbed</li><li>Drug absorption decreases with increasing molecular size</li><li>Increasing ionisation increases solubility (but could decrease permeability)</li><li>Systemic treatment formulations need to be readily absorbed by epithelial cells</li><li>Local treatment- formulation needs to remain in nasal cavity</li></ul></li></ul> Advantages of nasal formulation<ul><li>Avoids first pass metabolism</li><li>Large surface area for absorption</li><li>Good blood supply</li><li>Epithelium is permeable to small lipophilic drugs</li><li>Non- invasive</li><li>Easy to self administer</li></ul> Disadvantages of nasal formulation<ul><li>Limited to small delivery volumes - so potent drugs required</li><li>Mucociliary clearance/ barrier provided by mucus decreases absorption of some drugs</li><li>Enzymatic activity leads to degradation of drug compound</li><li>Low epithelial permeability for hydrophilic drugs</li></ul> Advantage of drug delivery via the lungs:<ul><li>Large surface area</li><li>Highly permeable membrane</li><li>Rich blood perfusion</li><li>Lack of mucociliary clearance</li><li>Painless</li><li>Natural</li><li>Immunotolerant</li><li>Avoid first pass metabolism</li><li><img alt="Pulmonary drug delivery - Advantages Rapid Onset of Action Lack of first-Pass metabolism Less Systemic Side effects Targeted Drug Delivery Lower Systemic Absorption " src="https://knowt-user-attachments.s3.amazonaws.com/347983bd-cb15-476f-94b1-8e91d45e4bdb.png" /></li></ul> Mechanisms of particles deposition in lungs:<ul><li>Inertial impaction<ul><li>When inhale the drug the particles hit the walls of the respiratory tract, making them deposit in the place they hit</li></ul></li><li>Gravitational sedimentation<ul><li>Larger particles due to gravitational forces get stuck to respiratory tract</li></ul></li><li>Electrostatic deposition <ul><li>Some formulation may be positively or negatively charged</li><li>A positively charged particle will be attracted to negatively charged cells in the respiratory tract</li><li>Negatively charged particle will be repelled by the negatively charged cells of the respiratory tract (so formulation needs to be adjusted to what target aiming for</li></ul></li><li>Interception<ul><li>As particles travel down respiratory tract they can get very close to the mucus layer of the lungs and become stuck</li></ul></li></ul> <ul><li>Brownian:<ul><li>Smaller particles (less than 0.5 micrometres) have Brownian motion which is the continuous movement of the particles.</li><li>Particles come in contact with the wall and stay in place where they come in contact</li></ul></li><li><img alt="sedimentation " src="https://knowt-user-attachments.s3.amazonaws.com/61da4618-197c-498a-91f1-b1caeee72344.png" /></li></ul> Devices for drug delivery to the lungs:<ul><li>Nebuliser:</li><li>Uses high frequency vibrations to break the particles and uses a flow to push the drug from the device to the patient</li><li>Jet nebuliser is most common</li><li>Drug needs to be dissolved in water based solvent</li><li>Can be solution of solid drug particles</li><li>High doses can be delivered- frequent use isn't required</li><li>Patients need to be static, longer time application so may not be suitable for children</li><li>PMDI's</li><li>(Pressurised metered dose inhaler)</li><li>Drug in solution or suspension</li><li>Drug is dissolved in a propellant or solution</li><li>Need to be shaken before use to allow even distribution of drug</li><li>Upon release propellant evaporates first so droplets of drug formulation remain</li><li>Spacers</li><li>Make it easier to use PMDI</li><li>Provide more time for propellant to evaporate so patient is only consuming drug</li><li><img alt="pMDl Accessory De%i€eo.. •t. • spacers pMD1 Loss Ectrostatk charge PATIENT Son cosevent Norvvoiatiie Dissolved drug or partos suspended " src="https://knowt-user-attachments.s3.amazonaws.com/55fa14d6-af53-4b00-9370-1827b3a2ca24.png" /></li><li>DPI's</li><li>(Dry powder inhalers)</li><li>Solid prepartion</li><li>Humidity can lead to agglomeration of particles</li><li>Only excipent is carrier particles (lactose)</li><li>Deliver larger doses than PMDI's</li><li>Patients with impaired lung function are unable to use these as they are unable o get the drug from the inhaler</li><li>Mixed powder can reduce electrostatics and reduced agglomeration</li></ul><img alt="Comparison pMDl

Portable and compact
No preparation
No contamination risk
Reproducible dosing
Cost effective Actuation-inhalation coordination High oropharyngeal deposition No dose counter DPI Portable and compact No need for actuation- inhalation coordination No propellant Dose counters included Short treatment time Dose dependent on the inspiratory force Single dose DPIs require dose preparation Humidity and heat may alter the performance Costly Nebuliser
High doses can be delivered
easy to administer for any patient population

Bulky Expensive High wastage of drug Requires preparation
Long treatment times Some require power source " src="https://knowt-user-attachments.s3.amazonaws.com/02032169-395f-4d20-9d0c-284f1434af72.png" />Testing:<ul><li>Aerodynamic assessment</li><li>Particle size distribution</li><li>Spray pattern and plume geometry</li><li>Stability testing</li></ul>