Courses:Pulmonary Drug Delivery/Formulation of aerosol
From Pharmpedia
< Courses:Pulmonary Drug Delivery
4.Formulation of aerosol 4. What are the different components of aerosol formulation? What are different types of formulation? Explain in detail the different types of formulation giving the principle behind each type with suitable examples
A. The aerosol product essentially consists of two components: 1.Product concentrate 2.Propellant
I.The Product concentrate consists of: 1.Active ingredients or mixture of active ingredients 2.Other necessary agents such as solvents, antioxidants and surfactants. II.The propellant may be single propellant or a blend of various propellants. This is equivalent to other vehicles used in pharmaceutical formulations. Just as a blend of solvents is used to achieve desired solubility characteristics or various surfactants are mixed to get the desired HLB value for an emulsion system, the propellant is selected to give the desired vapor pressure, solubility and particle size. III.Since one must be familiar with the physicochemical properties of surfactants, solvents and suspending agents, it follows that the formulation of aerosol preparation must be thoroughly familiar with propellants and the effect of propellants on the final product. Propellants can be combined with active ingredients in many different ways producing products with varying characteristics. Depending on the type of aerosol system utilized, the pharmaceutical aerosol may be dispensed as a fine mist, wet spray, and quick – breaking foam, stable foam, semi-solid or solid. The type of system selected depends on many factors: 1.Physical, chemical and pharmacological properties of active ingredients and 2.Site of application
The different types of aerosol formulation can be classified as follows: 1.Solution system or Two phase system 2.Water-based system or Three phase system 3.Suspension or dispersion systems 4.Foam Systems a.Stable foam b.Aqueous stable foam c.Non aqueous stable foam d.Quick breaking foam 5.Intranasal aerosol.
Solution system: A large number of aerosols can be formulated as a solution system which consists of two phases: a vapor phase and a liquid phase. Here the active ingredient is soluble in the propellant and thus forms a solution of the drug or active ingredient. Depending on the type of spray required, the propellant many consist of:
1. Propellant 12 or A-70 (which procedure very fine particles because of higher vapor pressure)
2. A mixture of propellant 12 and other propellants. If the other propellants have lower vapor pressure, the pressure of the final system decreases resulting in larger particles. Also lowering of the vapor pressure is produced through the addition of less volatile solvents such as ethyl alcohol, propylene glycol, ethyl acetate, glycerin and acetone. These are solvents added to increase the solubility of drug in the propellant. The amount of propellant used may vary from 5% for foams to 95% for inhalation products of the entire formulation. Spray systems with large particles are also useful topical preparations, since they tend to coat the affected area with a film of active ingredients.
Example 1 Sl.No. Contents Weight % 1. Active ingredient 10-15 2. Propellant 12/11 (50:50) to 100
Prop 12/11 30:70 Oral inhalation aerosols Prop 12/114 45:55 Prop 12/114 55:45
Metal container glass container Prop 12/114 (20:80) or (10:90)
Example 2
Sl.No. Contents Percentage
1. Isoproterenol HCl 0.25 2. Ascorbic acid 0.10 3. Ethanol 35.75 4. Propellant 12 63.90
For asthma 15 to
30 ml Stainless steel,
Aluminum. or glass
container
Aerosol intended for inhalation or local activity in the respiratory system in the treatment of asthma.
Example 3 Since propellant 12 has a relatively high vapor pressure, prop 114 is added to reduce the vapor pressure. Sl.No. Contents Percentage 1. Octyl nitrite 0.1 2. Ethanol 20 3. Prop 114 49.2 4. Prop 12 30.7
Example 4
Sl.No. Contents Percentage 1. Active ingredients up to 10-15 2. Solvents such as ethanol or propylene glycol 10-15 3. Distilled
water 10-15 4. Hydrocarbon Prop A-46 55-70
In the above example, hydrocarbon propellant has been used for topical preparations. Since the vapor pressure is low the product is packaged in plastic coated glass bottles.
Water based systems Or three phase system contain large amounts of water added to replace all or part of the non aqueous solvent used in aerosol. Depending on the formulation, they are emitted as a spray or foam to produce a spray, the formulation must consist of a dispersed active ingredients and other solvents in an emulsion system in which the propellant is in the external phase. In this way, when the product is dispensed, the propellant vaporizes and dispenses the active ingredients into minute particles. Since propellant water and most not miscible , a three phase aerosol forms ( propellant phase, water and vapor phase)
Formulation 1.Ethanol has been used as a co solvent to solubilise some of the propellant in the water. It also produces smaller particles. 2.Surfactants used to get a homogenous dispersion Spans – Span 20,40,60 & 80. Glycerol and glycols including long chain fatty acid esters of polyhydric compounds including glycols. Surfactant concentration is 0.5 to 2.0%. 3.Propellant concentration varies from 25 – 60%.
Suspension or Dispersion Systems Various methods have been used to overcome the disadvantages of a cosolvent of propellant – specially alcohol is flammable and causes chilling sensation. One method is to suspend or disperse the drug in a propellant or mixture of propellants to prevent or decrease the rate of settling of disperse particles, various surfactants or suspending agents are added to the system.
Example 1
Sl.No. Contents Percentage 1. Ephedrine bitartarate (with in 1-5 ) 0.50 2. Sorbitan trioleate 0.50 3. Prop 114 49.50 4. Prop 12 49.50 Oral inhalation aerosol for pulmonary delivery
In this formula, ephedrine bitartarate has minimum solubility in the propellant system, but is sufficiently soluble in the fluids
in the lungs to exert the therapeutic activity.
Example 2
Oral inhalation aerosols
Sl.No. Contents quantity 1. Isoproterenol sulfate 33.3mg 2. Oleayl alcohol 33.3mg 3. Myristyl alcohol 33.4mg 4. Prop 12 7.0gm 5. Prop 114 7.0gm
Physical stability of aerosol dispersion can be increased by 1.Control of moisture control 2.Use of derivatives of the active ingredient having minimum solubility in the propellant system 3.Reduction of the initial particle size to less than 5. 4.Adjustment of density of propellant and suspended particles so that they are equalized and 5.Use of dispensing agents.
Example 3 Oral inhalation product containing a steroid for treating asthma.
Sl.No. Contents Quantity 1. Steroid compound 8.4mg
2. Oleic acid 0.5mg
3. Prop 11 4.7gm 4. Prop 12 12.2gm
1. If moisture content of suspended particles is more it may result in agglomeration because of particle size growth. This may result in valve clogging, inaccuracy of dose, damage to liner and also be to the container. Therefore moisture content of the suspended drug particles is maintained, at less than 300 ppm. This is achieved by passing through various desiccators containing desiccants.
2. If the drug dissolves partially in the vehicle in which it is suspended, this may result in the particle size growth and finally agglomeration. Therefore to overcome this problem a chemical derivative or salt which has minimum solubility in the propellant vehicle must be selected. However, the drug must be soluble in the fluids surrounding lung tissue.
Eg., Ephedrine bi tartarate is the salt of ephedrine used in suspension
formulation while ephedrine hydrochloride is used in formulating solution aerosols since it is soluble in hydroalcoholic solution.
3. Rate of agglomeration of suspected particles can be reduced by maintaining uniform particle size in the range of 1 to 5. Particle size also necessary to reach the intended site of action. For topical formulations, particle size not to be greater than 50 in size. Reduction in particle size brought about by grinding equipment.
4. Density of suspended material and the propellant is equalized by adding inert material to the suspended particles, which may have either more or less density so that the suspended particles have the same density as the propellant.
5. Various surfactants and lubricants may be added to control the rate of agglomeration. Such agents include, isopropyl myristate, mineral oil etc. The surfactant prevents agglomeration of the suspended particles and also acts a valve lubricant. It should have a HLB value less than 10 used in 0.01 to 1 % conc., e.g. sorbitan monolaurate, sorbitan mono oleate and sorbitan sesqui oleate, sorbitan tri oleate.
Foam Systems
Foam systems are mainly used for external preparations and not used for pulmonary delivery. However, they form an essential part of the aerosol product and has therefore been described in detail below. Emulsion and foam aerosols consist of active ingredients, aqueous or non-aqueous vehicle, surfactant and propellant and are dispersed as stable or quick breaking foam depending on the nature of the ingredients and the formulation. The liquefied propellant is emulsified and is generally found in the internal phase. Non-aerosol emulsions are usually in lotion or viscous liquid form, but aerosol emulsions are dispensed as foams and can be advantageous for various applications involving irritating ingredient or when the material is applied to a limited area.
Aqueous stable foams
As the name indicates, aqueous stable foams contain water as the vehicle. In order to impart stability to the formulation, a large concentration of lipids are incorporated as an oil in water emulsion. The general formula for the foam, the different types of lipids used and their concentration are given below:
General Formula
Active ingredients
Oil waxes O/W surfactants 95 – 96.5 % w/w Water
Hydrocarbon propellant 3.5 – 5.0 %
Formula for Emulsion base
Sl.No. Contents Quantity (%w/w) 1. Myrisitic acid 1.33 2. Salicylic acid 5.33 3. Acetyl alcohol 0.50 4. Lanolin 0.20 5. Isopropyl myristate 1.33 6. Triethanol amine 3.34 7. Glycerin 4.70 8. Poly vinyl pyrollidone 0.34 9. Water 82.93
Final formula
Active ingredients – 2.0 % w/w Emulsion base 94-95% w/w Hydrocarbon propellant 3.0 to 4.0 – or compressed gas propellant.
The active ingredients may be made up of steroids, anti-bacterials and antiseptics.
Non aqueous stable foams Non-aqueous stable foams are formulated by the use of various such as polyethylene glycol. A
general formula is given by: Glycol 91.0 – 92.5 % Emulsifying agent such as propylene glycol mono stearate and other glycol
esters 4 % Hydrocarbon propellant 3.5 – 5.0%
Various medicinal agents are added into the base.
Quick – Breaking Foams
Here, the propellant is present in low concentration and in the external phase. When the product is dispensed it is emitted as a foam which immediately collapses into liquid. Applicable to topical medication, applied to limited or large areas without the use of a mechanical force to dispense the active ingredients
Example
Ethyl alcohol 46.0 – 66.0 % Surfactant 0.5 – 5.0 Water 28.0 – 42.0 Hydrocarbon propellant 3.0 – 15.0
Surfactant can be of the non-ionic or cationic type it should be soluble in both alcohol and water. If the proportion of ingredients is varied, foams may be obtained having a wide range in stability.
Intranasal Aerosols: Drug delivery systems intended for the deposition of medication into the nasal passageways has long been used as an effective means of administering drugs intended to produce either local or systemic effect. Traditionally, the modes of administering intranasal preparation have been limited to nasal drops, nasal sprays (non-pressurized) inhalants, intranasal gels (jellies), cream and ointments. A new alternative is the pressurized metered nasal aerosol. Advantages: 1.Delivery of a measured dose of drug. 2.Excellent depth of penetration into the nasal passageway with minimal inadvertent penetration into the lungs. 3.Reduced droplet or particle size. 4.Lower dosage 5.Maintenance of sterility form dose to dose. 6.Greater patient compliance 7.Decreased mucosal irritability and 8.Greater flexibility in product formulation.
Examples: 1.Decadron Turbinaire which is a pressurized aerosol suspension containing dexamethasone sodium phosphate which is used in allergic or inflammatory nasal conditions. 2.Beconase and Vancenase – Pressurized aerosol suspension containing Beclomethasone dipropionate in seasonal and perennial rhinitis.
Formulation Mainly suspension formulation: Active ingredients ( micronized) up to 1.0 % weight Dispersing agents, additives, solvents up to 1.0 weight Prop 12/11 (60:40) up to 98% weight
Retrieved from "http://www.pharmpedia.com/Courses:Pulmonary_Drug_Delivery/Formulation_of_aerosol"
This page has been accessed 471 times. This page was last modified 23:10, 25 December 2005. All content, except where otherwise noted, is licensed under a Creative Commons Attribution License.
