Pharmaceutical Aerosols: General formulation and MCQs for GPAT, NIPER, Pharmacist and Drug Inspector exam

Pharmaceutical Aerosols: General formulation and MCQs for GPAT, NIPER, Pharmacist and Drug Inspector exam

Aerosol formulation: Topical pharmaceuticals may be formulated as aerosols using solutions, suspensions, emulsions, powders, and semisolid preparations, while MDIs are formulated as solutions or suspensions.

Solution aerosols – Topical aerosols consist of a solution of active ingredients in pure propellant or a mixture of propellant and solvents. The solvent is used to dissolve the active ingredients and/or retard the evaporation of the propellant. Solution aerosols are relatively easy to formulate, provided the ingredients are soluble in the propellant. However, the propellants are non-polar in nature and in most cases are poor solvents for some of the commonly used medicinal ingredients. Through use of a solvent that is miscible with the propellant, one can achieve varying degrees of solubility of the active ingredient. For topicals (isopropyl alcohol, isopropyl myristate, polyethylene glycols, etc.), ethyl alcohol has found the greatest use, although some other solvents may be of limited value. For those substances that are insoluble in the propellant or propellant/solvent system, a dispersion or suspension can be produced. In this case the drug must be micronized so that the particles are less than 10 micrometers in average diameter. Topical pharmaceutical solutions are formulated using the hydrocarbon propellants, butane, isobutene, and propane. Although butane and isobutene can be used individually, the hydrocarbons are generally used as a blend. Other non-MDIs are formulated as aqueous solutions (eye care, etc.) and utilize nitrogen as the propellant. These are packaged as a conventional aerosol or utilize a barrier system.

Dispersions (powder aerosols) – These aerosols are similar to solution aerosols except that the active ingredients are suspended or dispersed throughout the propellant or propellant and solvent phase. This system is useful with antibiotics, steroids, and other poorly soluble compounds. Problems associated with the formulation of this system include agglomeration, caking, particle size growth, and valve clogging. Some of these problems have been overcome through use of lubricants such as isopropyl myristate, sorbitan trioleate, oleic acid, or other substances that provide slippage between particles of the compound as well as lubricating component parts of the valve. Surfactants also have been used to disperse the particles. The use of dispersing agents such as sorbitan trioleate, oleic acid, or lecithin is useful in keeping the suspended particles from agglomerating. Thought also should be given to both the particle size and the moisture content of the powder. The moisture content should be kept between 100 and 300 ppm or less, depending upon the type of product, and the propellants and solvents must be dried by passing them through a drying agent. The particle size for metered-dose inhalants should remain in the micrometer range and should be between 2 and 8 micrometers or less, with a mass median diameter of between 3 and 6 micrometers.

Emulsions – An emulsion system is useful for a great variety of topical pharmaceutical products. Since these systems contain a relatively small amount of propellant (4 to 10 percent), there is little, if any, chilling effect. Active ingredients that may be irritating if inhaled can be used as a foam. Depending on the nature of the formulation and the manner in which the product is to be used, the foam is aqueous or nonaqueous and can be stable or quickbreaking.

Emulsions can be dispensed from an aerosol container as a spray, stable foam, or quick-breaking foam, depending on the type of valve used and the formulation. Two types of emulsions can be formulated for use in an aerosol. A W/O emulsion is one in which the water phase is dispersed throughout the oil phase; an O/W emulsion is one in which the water is the continuous phase. If the product concentrate is dispersed throughout a propellant, the system behaves similarly to a W/O emulsion. However, since the propellant is in the external phase, the product is dispersed as a wet stream rather than as a foam. When the propellant is in the internal phase (O/W), a foam will be produced. The consistency and stability of the foam can be modified by choice of surfactants and solvents used. Many water-based aerosols are of the W/O type, in which the propellant is in the external phase. Stable shave-cream foams, on the other hand, are produced by keeping the propellant in the internal phase.

The stable foam is similar to a shaving-cream formulation, into which therapeutically active ingredients are incorporated. The foam is dispensed and rubbed into the skin or affected area. By substituting glycols and glycol derivatives for the water in an emulsion, a nonaqueous foam is obtained. The foam stability can be varied by the choice of surfactant, solvent, and propellant. It has been suggested that these foams are applicable to ointment bases, rectal and vaginal medication, and burn preparations.

A quick-breaking foam allows convenient and efficient application of medication. In certain instances the product was dispensed as a foam that quickly collapsed. This was useful in covering large areas with no rubbing necessary to disperse the medication. These quick-breaking foams consist of alcohol, surfactant, water, and propellant.

Table 1 – Metered-dose Inhalants (solution and suspensions): prototype formulation

Solution (CFC, HFC):

Active ingredient(s): solubilized antioxidants: ascorbic acid

Solvent blends: water, ethanol, glycols

Propellants: 12/11, 12/114 or 12 alone; 134a, 227, 134a/227

Suspensions (CFC):

Active ingredient(s): micronized and suspended

Dispersing agent(s): sorbitan trioleate, oleyl alcohol, oleic acid, lecithin, etc.

Propellants: 12/11, 12/114, 12 or 12/114/11 suspensions(HFC)

Active ingredient(s): micronized and suspended solvent:ethanol

Dispersing agent(s): sorbitan trioleate, oleyl alcohol, oleic acid, lecithin, etc.

Propellants: 134a, 227, 134a/227

Or

Active ingredient(s): micronized and suspended propellants: 134a, 227, 134a/227

Formulation factors – Included among formulation factors are the physicochemical characteristics of the active ingredients, the particle size and shape of the drug, the type and concentration of surface-active agent used, and, to some extent, the vapor pressure and the metered volume of propellants. In terms of physicochemical properties, the lipoidal solubility and pulmonary absorption rates of the active ingredient are of utmost importance. Another physicochemical factor governing the biopharmaceutics of a drug is its dissolution characteristics in pulmonary fluids. Drugs having a rapid dissolution rate in pulmonary fluids predictably produce much more intense and rapid onset of action, having a shorter duration than their less soluble derivatives. Therapeutic agents that exhibit very poor solubility in pulmonary fluids are to be avoided since they are likely to serve as irritants and precipitate bronchial spasms. The selection of the appropriate surface-active agent (required in most pressurized inhalation suspension aerosols) is another important consideration, since the surfactant will influence droplet evaporation, particle size, and overall hydrophobicity of the particles reaching the respiratory passageways and pulmonary fluids. Solubility of these dispersing agents or surfactants is limited when formulating with an HFC propellant. Ethyl alcohol has been added to increase their solubility.

Multiple choice questions:

1.Topical pharmaceuticals may be formulated as aerosols using

a)emulsions

b)powders

c)semisolid

d)all of these

2.MDIs are formulated as

a)solutions

b)suspensions

c)powders

d)a and b

3.For topical aerosols which of the following solvents are used?

a)isopropyl alcohol

b)isopropyl myristate

c)polyethylene glycols

d)all of these

4.For those substances that are insoluble in the propellant or propellant/solvent system, a dispersion or suspension can be produced.

a)true

b)false

5.In this case the drug must be micronized so that the particles are ______ in average diameter.

a)<10 micrometer

b)>10 micrometer

c)= 10 micrometer

d)none of these

6.Topical pharmaceutical solutions are formulated using

a)butane

b)isobutene

c)propane

d)all of these

7.Dispersion aerosols are useful with

a)antibiotics

b)steroids

c)poorly soluble compounds

d)all of these

8.Problems associated with the formulation of dispersions include

a)agglomeration

b)caking

c)particle size growth

d)all of these

9.Which of the following lubricants is/are used in dispersion aerosols?

a)isopropyl myristate

b)sorbitan trioleate

c)oleic acid

d)all of these

10.The particle size for metered-dose inhalants should remain in the micrometer range and should be

a)2-8 micrometers

b)5-10 micrometers

c)10-15 micrometers

d)2-10 micrometers

11.An emulsion aerosol system contain what percent of propellant?

a)4-10%

b)10-12%

c)50%

d)95%

12. Active ingredients that may be irritating if inhaled can be used as

a)spray

b)foam

c)wet stream

d)all of these

13.Quick-breaking foams consist of

a)alcohol

b)surfactant

c)water

d)all of these

14.In Metered-dose Inhalants(solutions) solvent blends used is/are

a)water

b)ethanol

c)glycols

d)all of these

15.In Metered-dose Inhalants(Suspensions) solvent used is/are

a)water

b)ethanol

c)glycols

d)all of these

 

Solutions:

  1. d)all of these
  2. d)a and b
  3. d)all of these
  4. a)true
  5. a)<10 micrometer
  6. d)all of these
  7. d)all of these
  8. d)all of these
  9. d)all of these
  10. a)2-8 micrometers
  11. a)4-10%
  12. b)foam
  13. d)all of these
  14. d)all of these
  15. b)ethanol

References:

  1. Remington Essential of Pharmaceutics, 1st edition 2013, page no. 644-648.

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