Classification of Aerosols 3
Aerosols may be classified as 1) Space Sprays 2) Surface coats 3) Foam
4.1) Space Sprays: These are finely divided sprays having particle size up to 50 um. E.g. Insecticides, Disinfectants and Room Deodorants etc.
4.2) Surface Coats: These are also sprays but disperse phase particles are coarse with sizes up to 200 um. They produce a wet coat when sprayed on a surface. E.g. Hair sprays, Powder sprays and topical medicament sprays.
4.3) Foam: these are produced by rapid expansion of propellants through an emulsion. Hence product comes out in the form of a foam or froth. E.g. Shaving cream and vaginal cream.
Inhalation dosage forms are the form of drugs or solutions of drugs administered through the (nasal or oral) respiratory route. Inhalers used for local action on the bronchial tree or for the systemic effects through absorption from the lungs.
Inhalation of a micronized powder directly administered into the lungs using a special breath activated device through inhalers only.
Depending on the physical state of the dispersed phase and continuous phase, inhalation system of drug is classified into three types
4.4 A. Pressurized metered dose inhalers (pMDIs)
4.4 B. Dry powder inhalers (DPIs)
4.4 C. Nebulizers
4.4. A. Pressurized Metered dose inhaler (pMDIs): 2, 3, 14, 15
The pressurized metered dose inhalers (pMDIs) consist of a canister, actuator and a spacer. The canister is composed of a metering dose valve with an actuating stem. The formulation (containing the active ingredient i.e. drug, a liquefied gas propellant and a stabilizer) is present in the carnister. The drug may be suspended or dissolved in the liquefied gas
propellant. Upon actuation, the metering dose valve is opened which releases a single metered dose of medication along with the liquified gas propellant to spray out of a carnister. This process is called "cavitation". The liquefied gas propellant is volatile in nature, which breaks down into liquid droplets and evaporates rapidly and the dried micronized drug are inhaled to the lung. Drawbacks of Pressurized metered dose delivery:
- Various chlorofluorocarbons (CFC) are used as the propellant, it causes depletion of ozone layer. So later it was replaced with hydro fluorocarbons. Hydro fluorocarbons cause greenhouse effect.
- pMDIs are pressurized forms and it emits the dose at high velocity and gets deposited in the oropharynx.
- The mixture of propellant and the cosolvent may extract some of the organic compounds from the device components leads to chemical degradation.
How to use inhaler (Spacers)
4.4 B. Dry powder inhalers (DPIs): 2, 3, 14, 15
The DPIs are very advantageous than pMDIs. Because
a) DPIs require no coordination of actuation and inhalation. It activated by patient's
b) DPIs donot extract organic compounds from the device components and the chances of degradation is less than pMDIs.
c) The rate of drug release / delivery is good than pMDIs.
d) These are efficient, more stable and easier to use than pMDIs.
- DPIs are composed of micronized powdered drug particles. The micronized powdered drug particles (of sizes < 5um) are mixed with much larger sugar particles (of size < 30 um) eg. Lactose monohydrate.
- The smaller drug particles forms loose aggregate with lactose monohydrate. The micronized powdered drug particles have high cohesive force, so they have a tendency of adhering to each other. The addition of large particle sized lactose monohydrate reduces the cohesive force of the micronized drug particles and form loose agglomerate with the micronized drug particles. It helps in an easy deaggregation of the agglomerates, upon inhalation, the agglomerates get broken down into its constituent particles, with the help of mechanical devices such as screens, on which the particles agglomerates impact.
- It releases the smaller sized powdered drug particles into the air to be inhaled to the lung. Here the larger sized lactose monohydrates particles are retain or left behind in the device and in the mouse throat.
DPI's are classified into two types
a) Unit dose devices b) Multi dose devices
a) Unit-dose devices:
Unit dose devices are re-useable or disposable single-dose dry powder inhalers. These are designed easy to use, economical and suitable for a wide range of conditions that require a rapid onset of effect or that are for occasional use. Generally Unit dose device is the filled in capsule placed in the device. The capsule shell is opened in the device and the powder is inhaled by the user. The capsule shell remaining in the device is to be discarded after use, so that the device can be reused with a new filled capsule. The unit dose devices cannot provide large dose as in the case of Asthma attack (Disadvantage).
Example for unit dose dry powder inhalers-
The InnovaTM (Inhale Therapeutic Systems (San Carlos, California and U.S.A.)) is a long term used unit dose dry powder inhaler placed in a transparent holding chamber consisting of a stored bolus of compressed air which generate aerosol independent of patient's effort. The holding chamber enables patients to view the aerosol to assure proper dosing. Further, the device is capable to fluidize and extract up to 90% of the dose from the reservoir, So that waste is minimised and enhancing the accuracy and precision of the dosage.
The SoloTM device is a short term used patient-driven unit dose dry powder inhaler. It has a built-in flow control to maximize the reproducibility of dose to patient.
b) Multi dose Devices:
Turbuhaler was the first developed multi dose DPIs by A.B. Draco (now a division of Astra Zeneca) capable of delivering carrier-free particles at moderate flow rates. However, one of the drawbacks of the Turbuhaler is that it has a variable rate of delivery due to different flow rate. To work out with the drawback and for multiple dosing and consistent performances, Turbuhaler was replaced by Diskhaler developed by Glaxosmith.
Diskhaler was used to deliver several drugs like salbutamol and beclomethasone etc., this device uses a circular disk containing of either four or eight powder doses that are maintained in separate aluminum blister reservoirs. On priming the device, the aluminum blister is pierced and the contents of the pouch are dropped into the dosing chamber. This product had limited commercial success and was superseded in the late 90's by the Diskuse.
Diskuse is a true multi dose device, having 60 doses in a foil- foil aluminum strip that is opened only at the point just prior to patient inspiration. Consistent performance and most patient acceptance is allowed the Diskuse to become the gold standard of multi dose powder delivery devices. Others like the GyroHaler(r) and OmniHaler(r) are economical, multi-unit dose dry powder inhaler designed to deliver locally acting drugs to the lungs.
Clickhaler(r) is a multi-dose, reservoir dry powder inhaler. It is approved for use to deliver a number of drugs used to treat patients with asthma and COPD (salbutamol, beclometasone, formoterol, budesonide and procaterol) in Europe and Japan. Clickhaler(r) is an automated inexpensive multi - unit dose DPI device.
Duohaler(r) is a fixed dual-therapy, passive, multi-dose dry powder inhaler where two individual drug formulations are placed in two separate drug reservoirs that feed to two separate metering chambers from which the drugs are delivered to the user in the same breath.
PowderHale(r) is Vectura's patented dry powder inhaler technology, designed as to allow suspended drug particles to achieve high lung penetration with low dose. This is achieved by using inactive excipient, known as a Force Control Agent (FCA) to the drug formulation.
DPIs major drawbacks as:
a. The dispensing / generalisation of aerosol depend on patient's inspiratory airflow.
b. DPIs suffer from dose uniformity problems.
c. Complex/expensive development and manufacturing process.
d. It may lead to pharyngeal deposition of the drug.
4.4 C. Nebulizers: 2, 3, 14, 15
Nebulizer is a device used to administer medication in the form of a mist inhaled through the lungs. Nebulizers use for oxygen, compressed air or ultrasonic power to break up medical solutions and suspensions into small aerosol droplets called mists that can be directly inhaled from the mouthpiece of the device. It produces a mist of drug containing water droplets for inhalation purpose. The powdered drug is present either in solution form or suspension form in the nebulizer.
Advantages of nebulizers:
- Patient coordination not required.
- Effective with tidal breathing.
- High dose possible.
- No chlorofluorocarbon (CFC) is released.
- Nebulizers used with supplemental oxygen.
- Can use for combination therapy if compatible.
- The ultrasonic nebulizer is faster in delivery, smaller and portable.
Disadvantages of nebulizer:
- They are expensive.
- Electrical power or battery sources are required.
- Jet nebulizer requires pressurized form of gas.
- The frequent cleaning required.
- There is a chance of contamination.
- The suspension of dosage cannot be properly aerosolized.
- The jet nebulizer produces large and different sizes of particles.
- The ultrasonic stimulation and rise in temperature may cause degradation of drug.
Nebulizers are usually of two types:
i) Electronic nebulizer and
ii) Jet or ultrasonic nebulizer.
Jet or ultrasonic nebulizer uses a source of pressurized air to blast a stream of air through a drug containing water reservoir, producing water droplets. In contrast, electronic nebulizers develop mechanical vibration to produce water droplets.
The nebulizers are generally used for the treatment of acute conditions (e.g. acute asthma, respiratory infection) or in those patients who have difficulties using other respiratory dosage forms.
Some of the Nebulizers of marketed products:
Omron Microair Nebulizer:
The features of Omron Microair Nebulizer are:
- A therapeutic aerosol is works by electronic vibrating mesh technology.
- It delivers contents completely.
- It consists of universal adapters.
- As its lightweight weighs only 6 ounces (170 g) with batteries, so easily portable.
- Ideal for pediatric asthma treatment.
- It saves energy due to low power consumption. [4 hours of continuous operation on 2 alkaline batteries (batteries sold separately) 8 hours when used about 30 minutes a day.]
- It is smallest size of electronic nebulizer.
- For easy cleaning detachable nebulizer head is present.
- It is replacement for Metered Dose Inhalers (MDI).
DeVilbiss DeVilbiss PulmoMate Compressor / Nebulizer provides an incomparable combination of quality and value. Its design has been made in such a way that it fits easily into luggage, backpacks for easy transport. The DeVilbiss PulmoMate features an updated compressor/motor for longterm durability and performance.
Pari Trek S is the best compressor nebulizer machine for travelling. This nebulizer include a DC car adapter and good looking portable case which help those who travel a lot by making nebulization treatments in the car possible.
4.5) Intra Nasal Aerosols:
This topic already described in aerosol systems.