Prepared by:Krupali Antala

En.no:1508212202001

Pulmonary drug delivery system

PARUL INSTITUTE OF PHARMACYDEPARTMENT OF PHARMACEUTICS

LIMDA, WAGHODIA, VADODARA

Anatomy Formulation Devices:I. dry powderII. pressurised meter dose inhalerIII. nebulizer Advantages Disadvantages

Contents:

The vestibular region: It is located at the opening of nasal passages and is mainly responsible

for restricting entry of air borne particles. The respiratory region: The respiratory region is the largest having the highest degree of

vascularity. The respiratory region contains three nasal turbinate: superior, middle, and inferior which project from the lateral wall of each of the nasal cavity.

The olfactory region The olfactory region is situated between the nasal septum and the

lateral walls of each of the two nasal cavities and just below the cribriform plate of the ethmoid bone separating the cranial cavity from nasal cavity.

Anatomy of nasal route

Types of dosage forms and delivery systems Nasal drops are the simplest and the most convenient nasal pharmaceutical form, but the exact amount of drug delivered is not easily quantified and often result in overdose. Moreover, rapid nasal drainage can occur when using this dosage form.

Solution and suspension sprays are preferred over powders sprays because the last one easily prompted the development of nasal mucosa irritation.

Recently, gel devices have been developed for a more accurate drug delivery. They reduce postnasal drip and anterior leakage, fixing the drug formulation in nasal mucosa. This enhances the drug residence time and diminishes mucociliary clearance, thereby, potentially increases nasal absorption. Over the last few years, specialized systems such as lipid emulsions, microspheres, liposomes and films have also been developed to improve nasal drug delivery.

Formulation properties which affect nasal drug delivery

This enhances the drug residence time and diminishes mucociliary clearance, thereby, potentially increases nasal absorption. Over the last few years, specialized systems such as lipid emulsions, microspheres, liposomes and films have also been developed to improve nasal drug delivery

Physical form of formulation: Nasal drug absorption depends on the physical form of the

formulation. A powder form was found to be more effective than liquid formulations because powder is not readily washed out with the nasal secretions.

Cont..

Dry Powder Inhalation (DPI) Devices

The Pressurized Metered-Dose Inhalation (pMDI) Device

Nebulizers

Pulmonary Drug Delivery Devices

DPIs are used to treat respiratory diseases such as asthma and COPD, systemic disorders such as diabetes, cancer, neurological diseases (including pain), and other pulmonary diseases such as cystic fibrosis and pulmonary infectious diseases

Devices requiring the patient's inspiration effort to aerosolize the powder aliquot are called passive devices because as they do not provide an internal energy source

Active devices provide different kinds of energy for aerosolization: kinetic energy by a loaded spring and compressed air or electric energy by a battery

Dry Powder Inhalation (DPI) Devices

Most DPIs contain micronized drug blended with larger carrier particles, which prevents aggregation and promotes flow

Cont…

Principle of dry powder inhaler design

Dose type # 3 Capsule Dose range From µg to 50 mg Pressure Drop kPa at 35 L/min. Performance

substantially flow-independent 25 L/min.

Lifetime 30 to 60 capsules (one month’s use)

Componants Three, Plastic Performance Lactose-based, fine particle

fraction: 20 – 50% Particle engineered, FPF: 50 – 80%

Patent Filed in 2010 Uses Chronic or acute uses

Formulation

The pressurized metered-dose inhalation (pMDI) device was introduced to deliver asthma medications in a convenient and reliable multi-dose presentation

The key components of the pMDI device are: container, propellants, formulation, metering valve, and actuator

The pMDI container must withstand high pressure generated by the propellant. Stainless steel has been used as a pMDI container material. Aluminum is now preferred because, compared to glass, it is lighter, more compact, less fragile, and light-proof

The Pressurized Metered-Dose Inhalation (pMDI) Device

Drug Brand Main

Excipients Supplier Main Indications

Olapatadine Patanase Benzalkonium chloride, dibasic sodium phosphate,

Alcon Laboratories

Mometasone

Nasonex Microcrystalline cellulose, carboxymethylcellulose sodium, benzalkonium chloride

Schering-Plough

Management/treat ment of symptoms of seasonal and perennial rhinosinusitis

Formulation

Coatings on the internal container surfaces may be useful to prevent adhesion of drug particles and chemical degradation of drug

Propellants in pMDIs are liquefied, compressed gases that are in the gaseous phase at atmospheric pressure but form liquids when compressed

They are required to be nontoxic, nonflammable, compatible with drugs formulated either as suspensions or solutions, and to have appropriate boiling points and densities

The Pressurized Metered-Dose Inhalation (pMDI) Device

Using MDI without Spacer

A nebulizer is a device used to administer medication to patient in the form of a mist inhaled into the lungs

It is commonly used in treating cystic fibrosis, asthma, and other respiratory diseases

There are two basic types of nebulizers:◦ The jet nebulizer functions by the Bernoulli principle by which

compressed gas (air or oxygen) passes through a narrow orifice, creating an area of low pressure at the outlet of the adjacent liquid feed tube. This results in the drug solution being drawn up from the fluid reservoir and shattering into droplets in the gas stream

◦ The ultrasonic nebulizer uses a piezoelectric crystal, vibrating at a high frequency (usually 1–3 MHz), to generate a fountain of liquid in the nebulizer chamber; the higher the frequency, the smaller the droplets produced

Nebulizers

rapid absorption, higher bioavailability, therefore, lower doses;

• fast onset of therapeutic action; • avoidance of liver first pass metabolism; • avoidance of metabolism by the gastrointestinal tract; • avoidance of irritation of the gastrointestinal membrane; • reduced risk of overdose; • non-invasive, therefore, reduced risk of infectious disease

transmission; • ease of convenience and self-medication; • improved patient compliance; • can be a beneficial adjunct product to an existing product

Advantages

mucociliary clearance reduces the residence time of drug;

• not applicable to all drugs; • insufficient absorption due to lack of adequate

aqueous solubility; • require high volume of dose (25-200 ml)

depending on aqueous solubility of drug; few drugs can cause nasal irritation;

• few drugs may undergo metabolic degradation in the nasal cavity;

• less suitable for chronically administered drugs;

Disadvantages

Physiological factors- 1.Mucocilliary Clearance 2.Enzymatic Degradation Low Bioavailability Physic-chemical factors 1.dissolution rate 2.particle size 3.solubility 4.molecular weight 5.partition coefficient 6.polymorphism,

Factors Affecting Nasal Drug Absorption

pH of the formulation Osmolarity Non-aqueous nasal sprays

Formulation factors

Types of Inhalers Metered Dose Inhalers

(MDI)•These inhalers use a chemical propellant to force a measured dose of medication out of the inhaler.

•It may be easier to use a MDI with a spacer (a short tube that attaches to the inhaler )

• Dry Powder Inhalers (DPI)

•No chemical propellant. Medication released by breathing in more quickly with a traditional MDI

•easier to use than the conventional pressurized MDI because hand-lung coordination isn't required

•Spacers shouldn't be used with dry powder inhalers

Sanjay Dey1*, Beduin Mahanti1, Bhasakar Mazumder2, Nasal drug delivery: An approach of drug delivery through nasal route, Pelagia Research Library, Der Pharmacia Sinica, 2011, 2 (3): 94-106.

Cecilia Wadwll, In vitro studies on factors influencing permeability and implications on absorption, Thesis Uppsala University, 2002.

S. B. Patil, R. S. R. Murthy, Preparation and in vitro evaluation of mucoadhesive chitosan microspheres of amlodipine besylate for nasal administration, Indian journal of pharmaceutical sciences January - February 2006:64-67.

Reference

Thank you