Innovat International Journal Of Medical & Pharmaceutical Sciences, 2016; 1(1)
EXCIPIENTS AND ITS VARIATION IN
PHARMACEUTICAL AEROSOL FORMULATION: A
REVIEW
www.innovatpublisher.com
Review Article
MAHENDRA PRATAP SWAIN1, *MAUNAB PATRA2, DR. MEENAKSHI PATNAIK3
Research Officer1,*Senior Research Officer2, MD & CEO3, Research & Development, ABBESS Healthcare OPC Pvt. Ltd., E-mailresearch@abbess.in,Website- www.abbess.in
Received 2016.10.27-Accepted 2016.11.18
Abstract
An aerosol can have variations in formulation as per the area of application and intention of use. In short aerosol formulations are the best NDDS for dispensing Active
Pharmaceutical Ingredients (API’s) to the systemic circulation as well as faster local action as compared to OSD. As this dosage form is applied topically, it does not
affect the major organs of the body. It has been concluded that it does not show or shows minimum hypersensitivity to locally applied area. It shows best bioavailability
as compared to the OSD & desired pharmacological effect. Now a days, new excipients are being used to used get the better formulation efficacy and for batter patient’s
compliance. According to the formulation to be processed, we should use specific excipients as conformed by the assay procedure in respective furmularary or
pharmacopoeia. From various excipients like colorants, disintigrants, antiadherants, lubricants, sweeteners, binders, flavourin agents, glidants, sorbents, preservatives
and vehicles, various dosage forms were formulated as per target and bioavailability. The present review is based on the excipients used in topical pharmaceutical
aerosols and its variations.
Key word: Topical Aerosol, Excipients, Variation, effect on formulation.
INTRODUCTION
Excipients are defined as inert, safe and nontoxic compound that could be added
to the drug formula to enhance the pharmaceutical and pharmacological properties
of dosage form.1 Excipients can be classified either according to their function or
according to the dosage forms they are being added to.
In general excipients such as diluents, fillers, disintegrating agents, lubricants,
glidants, sweetening agent, coloring agent, flavoring agent, solubility enhancer,
emulsifying agent, suspending agent, surface active agent, plasticizer used in
various dosage forms.[3] The fact that excipients are inert substances has been
changed with time since now. Some excipients have direct influence in
dissolution rate and drug absorption.[3] Furthermore some excipients had been
found to encounter some activity regarding the facilitation of penetration inside
the tumour cell. On the other hand some studies confirmed presence of some side
effects associated with presence of certain types of excipients, e.g. sucrose,
lactose, parabens, and menthol are associated with diabetes mellitus, stomach
cramps, hypersensitivity reaction, spasms of the larynx in infants, respectively.[3]
Since M.. Dou Vsa, P. Gibala, J. Havl'I Vcek, L. Pla Vcek, M. Tkadlecov'a, J. B
Vrich'a Vc discovered the phenylephrine in common cold formula is the cause to
degradation during pharmaceutical processes having saccharose.[4]
The use of excipients in pediatric formulations is one of the most important
challenges faced by the formulators. We cannot consider paediatrics
pharmacology as that of the adults because they have special and unique needs.
On the other hand the different anatomical and physiological features should be
considered in formulating pediatric dosage forms which make the formulation
difficult as far as compatibility, stability and palatability of the formula is
concerned. Cardiovascular, hepatic, respiratory and central nervous system
toxicity is found to be associated with the use of a general solvent propylene
glycol. Sucrose as sweetening agent, in higher concentration can cause dental
caries[6]. Hereby, we can conclude that excipients should not be considered any
longer inert, but we should do an extra effort to investigate the possible side or
toxic effect of the excipients in order to have safe formulation practice. Before
formulate on the aerosol spray, we have to go through the batter choice excipients
for a batter formulation.
An Aerosol i.e., pressurized packages, pressurized dosage forms is the best NDDS
for dispensing the API(s) to the systemic circulation as well as the local action.
An Aerosol is defined as "A disperse system, in which most fine solid drug
particles and/or liquid droplets get dispersed in to relevant propellant (gas), which
behave like continuous phase" or we can say in other word that "An Aerosol is
system which expels or actuate the contents from the container depending on the
pressure developed by compressed or liquefied gas". An aerosol is also defined
pressurized dosage forms containing one or more therapeutic active ingredients
which upon actuation emit a fine dispersion of liquid and/or solid materials in a
gaseous medium containing smaller than ≤ 45 µm".[7] In this preparation two
phases are combined: Dispersed phase and Continuous Phase, Dispersed Phase
may be solid and/or liquid and the Continuous phase is Gas or Propellant or blend
of propellants. Pharmaceutical aerosol has been playing an important role in the
healthcare profession and best wellbeing of millions people throughout the world
last many year. These products include pressurized MDIs,[9] DPIs,[10]
sublingual,[11] nebulizers,[12] topical sprays (coolants, local anaesthetics) and
dental sprays. The technology continual causes advancement, the ease of use, and
the more desirable pulmonary effect than IV bolus formulation for
systemicdrugs.[8] This has increased the attraction for the pharmaceutical aerosol
delivery system in recent years.[7] The term pressurized package is generally used
when referring to the aerosol container. Pressure is developed to the aerosol
system through the use of one or more liquefied or gaseous propellants.
As we need to add many spices to have nice cooked meal with enjoyable taste
reflecting the harmonization of different ingredients, it will be the same for as
case of in drug formulation as we need to add a many of additive to enhance the
performance of our dosage form.
Since the mid of 1950s, aerosol dosage forms of pharmaceuticals have played an
important role in treating respiratory illnesses such as asthma and COPD, and
today this MDIs & DPIs have become an important part of that treatment or
medication.[9]Administration of drugs by the pulmonary route is technically
challenging because oral deposition can be high, and variations in inhalation
technique can affect the quantity of drug delivered to the lungs. Therefore, there
have been considerable efforts to provide more efficient and reproducible aerosol
systems through improved drug delivery devices and through better formulations
that disperse more readily during inhalation.[5,6,8]
Advantages over other dosages forms
Mahendra Pratap Swain et.al
5
Table 1. Advantages of aerosol over other dosage forms
Aerosol
Other dosage forms
i. Contents can easily be withdrawn from the package without contamination or
exposure of the remaining material as it is packed in a tight and high strong
materials.
i. In case of OSD there are higher chances to contaminate through hand and also in
minute brakeage of packaging materials as it is so thin.
ii. Convenient to apply and administer without the help of others.
ii. Not so much convenient (Exception ODTs) and Help and guide are needed.
iii. The onset of action is very faster.
iii. Comparably not so much faster in OSD and Other dosage forms.
iv. Dispersion of APIs is very good and shows a batter pharmacological action
within a shorter period of time.
iv. Dispersion takes more time as well as absorption (show low efficacy on ADME
process of pharmacokinetic). So it relatively shows less pharmacological action.
v. Due to its closed packaging of aerosols, there is no direct contact with the
APIs.
v. In this case it’s not so as its packaging is thin and blistered.
vi. Aerosol formulation and its DDS avoid the decomposition or inactivation of
drug, due to the pH or enzymatic action of the stomach or intestine by oral
administration.
vi. Inactivation is generally seen as it direct contact with enzymes of food particles.
vii. Avoids the first pass metabolism (Presystemic metabolism)[17]& Hepatic
metabolism leeds to high drug absorption.
vii. Hear is shows first pass metabolism so less drug is go through ADME process.
viii. A specific amount of calculated dose or drug can be actuated from the
container without contamination.
viii. No specificity and shows contamination.
x. Hydrolysis of APIs and used excipients can be prevented since propellants do
not contain any moisture.
x. Hear moisture contact is high as it expose to environment leeds to hydrolysis of
drug excipients and APIs.
xi. It gives sterility to APIs, because microorganism can’t enter even when the
valve is opened.
xi. Comparatively no such sterile.
xii. The fastest volatilization of used propellants provides a cooling sensation
and refreshing effect causing the sinus activation that leads to dilation of blood
capillaries and muscle relaxation thus best result by APIs obtained.
xii. No volatilization in OSDs, so no cooling effect as well as no effective action.
xiii. Aerosol formulation, maintaining valve assembly control, the physical form
and particle size of the emitted product may increase efficacy of a drug.
xiii. Efficacy can be increase in case of Parenteral not in case of OSDs.
xiv. Irritation and Inflammation can be reduced by application of topical aerosol
APIs in a uniform thin layer to the skin without touching the affected area.[8]
xiv. As like aerosol no such irritation seen but in case of parenteral highly irritative
if not dispense properly.
Disadvantages of Aerosols

Aerosol formulations are highly flammable.[10]

Usually disposal of empty aerosol containers is difficult.

High volatility property of the propellant(s) can cause irritate on open
wounds.

Some persons may be hyper/ hyposensitive to the propellant(s) and
persons who inhalation aerosol(s), the fluorinated hydrocarbons may
causes carcinotoxic[11]or carcinogenic and Cyto-toxicity on repeated
use.

Aerosol packs needs to be kept away from high temp, because the
pressure develops inside can cause the container to collapse.

If the drug liquid formulation is not soluble in the propellant, then
aerosol formulation is difficult and difficult to achieve the proper
pharmacological outcomes.

Some of the propellant(s) may cause toxic reactions, therapy if
continued for a longer period of time.
Working Principle of Aerosols
In Aerosol DDS, propellant / propellant mixture and product concentrate is sealed
and packed within an aerosol container. Equilibrium is quickly established
between the portion of propellant that remains liquefied and the other which
remains at vaporized state. It occupies the upper portion of the aerosol container.
So, the vapour phase develops pressure in sealed container, against the walls. At
the end of dip-tube of valve assembly a liquid phase is situated which contains the
Innovat International Journal Of Medical & Pharmaceutical Sciences Vol 1 Issue 1 Nov-Dec 2016
liquefied gas and the product concentrate [API(s) + Excipients], liquefied gases
have high pressure & this pressure is responsible for actuation of the aerosols due
to increase in the valve forces. This forces pushes the liquid phase up to the dip
tube and through the orifice of the valve, contents get released into the
atmosphere.
As Propellant(s) get released in to environment by actuation, it expands and
evaporates within a short period of time because of the drop down in pressure,
which leaves only the product concentrate as airborne liquid droplets or dry
particles depending upon the type of formulation for subjected area So, by even
actuation of the product the pressure within the container remains constant and the
product may be continuously released at same rate and in same proportion.
After activation of the valve assembly in aerosol system, the pressure exerted by
the propellant(s), forces the contents of the package to sot-out through the orifice
of the aerosol valve assembly. The physical form of the formulation emitted,
depends on formulation type (selection of excipients used) and type of valve is
used. Generally, aerosol products designed as to expel their contents in the form
of a fine mist, a coarse, wet, or dry spray or simply as aero-dispersed form; a
steady stream; or stable or fast breaking foam.[13]
Important thing is when the liquid reservoir or formulation has just exhausted, the
internal pressure decreases. So the gas may be expelled from the container with
diminishing pressure until totally empty.
Excipients Used in Pharma Aerosols
Role of Key Solution/ Suspension Excipients
4-8
Mahendra Pratap Swain et.al
Water is the most widely used vehicle; due to: Lack of toxicity, physiological
compatibility,[14] and good solubilising power[14] (high dielectric constant), but
as it have the property;
Likely to cause instability of hydrolytically unstable drugs or polar drugs.
Good media for microbial growth
6
utilised in liquid drug formulations to increase the solubility of poor waters
soluble substances and/or to enhance the chemical stability of APIs.[16]
Polar co-solvents are used for: Enhance solubility, masking taste & smell and
anti-microbial effectiveness or stability. It also reduce the dose volume (e.g. oral,
injections) Or, conversely. Examples: propylene glycol, glycerol, ethanol, low
molecular weight PEGs.[8,9]
Non polar co-solvents, e.g. Emulsions / microemulsions using fractionated
coconut oils
Buffering Agents
Figure 1. Excipients used in Pharma aerosols
Sorbitol, dextrose etc.are often added as solubiliser, as well as base sweeteners, as
like pros and cons to water.
Solvents/Co-Solvents
Solvents are the chemicals that dissolves a solute (a chemically different liquid,
solid or gas), forms a solution. Solvents are usually liquid, but can also be a solid
or a gas. E.g.: organic solvents (Acetone, acetic acid, Acetonitrile, Benzene,
carbon tetrachloride, methylene chloride etc.) and inorganic solvents(liquid
ammonia, liquid sulfur dioxide, sulfuryl chloride and sulfuryl chloride fluoride,
phosphoryl chloride, dinitrogen tetroxide, antimony trichloride, bromine
pentafluoride, hydrogen fluoride, pure sulfuric acid etc.)
Co-solvents are defined as these are the water-miscible organic solvents that are
Buffering agents are the weak acids or bases used to maintain the acidity (pH) of
a solution near to 1 although after addition of another acid or base. pH of the
formulation is necessary in order to: Ensure physiological compatibility and
incompatibility, Maintaining or optimising stability of the chemical, antimicrobial effectiveness on formulation, Optimise solubility (or insolubility if taste
is an issu). E.g.:( Gifford, Sorensen, The Clark-Lubs etc are solutions and
Sodium bicarbonate, magnesium carbonate and sodium citrate etc. are
solute)[8,9,19]
Preservatives
A substance used to preserve the drug formulations, foodstuffs, wood, or other
materials against decay is so called as preservatives. Preservatives are used in
multi usable cosmetic/pharmaceutical products. It prevents an increased risk of
contamination and proliferation by opportunistic microbes, E.g. not required for
sterile,
single-dose
products.
Ideal properties of these type excipients mostly targeted for microbial cells and
have no toxicity/irritative effect towards mammalian cells. There are a limited
number of approved preservatives available for multiuse aerosol as well as OSDs,
and options are even more limited for other routes of administration. Should not
use in parenteral infusions.[8,9,10,18]
Some examples of various topical preservatives are:
Table 2. Examples of topical preservatives
Chemical class
Quaternary ammonium Compounds (QACs)
Preservatives
Benzalkonium chloride, cetrimonium bromide, benzethoniun chloride, alkyltrimethylammonium bromide
QACs/ metal chelator
Alkyl/ Aryl Alchol
Amino aryl acid ester
Alkyl/ aryl amides
Organomercurials
Bigunides
Phenol
QACs e.g. : EDTA/ Benzalkonium chloride
Benzoic acid, soric acid
Methyl, ethyl, propyl, butyl Parabens and combination
Chloroactamide, trichlorocarban
Thimerosal
Chlorhexidine
4-chlorocresol, 4-chloroxylenol, dichlorophene, hexachlorophene
Anti-Oxidants
A Chemical that decrease damagation of FPPs due to oxygen is called as Antioxidants. Now a day used antioxidants include enzymes and other substances.
Vitamin C, vitamin E, and beta carotene are capable of counteracting the
damaging effects of oxidation. Antioxidants are also generally used in food
products such as vegetable oils and prepared foods to prevent or delay their
deterioration from the action of air. These are used to control oxidation of APIs.
Preservative, e.g. potassium sorbate and Vehicle, e.g. oils or fats susceptible to βoxidation (rancidification); Colourants (ageing discolouration). [8,9,19]
Oxidation monitored by specific assay, Light exposure and metal ion impurities
can accelerate oxidative degradation and hence cause depletion of anti-oxidant.
Efficacy of this affected by incompatibility with other excipients somehow with
APIs, e.g., partitioning into micelles (from surfactants), Adsorption onto surfaces
(container, thickening agent and suspended particles), Interaction with metal ions
etc.
tragacanth, alginates, cellulose derivatives. It is also use as suspending agents and
encourages deflocculation if its levels is too low.[8,9,19]
Anti-Foaming Agents (Defoamer)
A substance used to reduce foam formation in liquid dosage formulation is called
anti foaming agents also called as Defoamer. Commonly in process of
manufacturing or when reconstituting of liquid dosage have this problem of foam
formation forms needs it due to undesirable and disruptive Anti-foaming agents.
These are effective to reduce foam by lowering surface tension and cohesive
binding of the liquid phase. Generally used antifoaming substances are insoluble
oils, polydimethylsiloxanes and other silicones, certain alcohols, stearates and
glycols. A typical example is Simethicone (polydimethylsiloxane-silicon dioxide),
which is used at levels of 1-50ppm. In addition to the process called wet
granulation using a foam rather than aqueous granulation fluid is gaining
popularity.[8,9,19]
Wetting Agents
Humectants
A chemical, added to liquid to reduce its surface tension and make it more
effective in spreading over and penetrating surfaces.
•Oral: polysorbates (Tweens), sorbitan esters (Spans)
•Parenteral: polysorbates, poloxamers, lecithin
• External: sodium lauryl sulphate
Exceptionally, these are cause excessive foaming and can lead to deflocculation
also form undesirable physical instability (sedimentation) if levels too high. In
other hand hydrophilic colloids that coat hydrophobic particles, e.g bentonite,
Innovat International Journal Of Medical & Pharmaceutical Sciences Vol 1 Issue 1 Nov-Dec 2016
These are important pharmaceutical as well as cosmetic ingredients used to
prevent loss of moisture thereby retaining the skin's natural moisture.
Hygroscopic excipients used about 5% in aqueous suspensions and emulsions for
external application. Generally these are used for prevent drying of the product
after application to/on the skin and prevent cap-locking caused by condensation
onto neck of container closure of a container after first opening.
Examples include: propylene glycol, glycerol, PEG.[8,9,10,19]
4-8
Mahendra Pratap Swain et.al
Preservatives
Propylene Glycol Toxicity
Propylene glycol (PG) batter and widely used solvent with anti-microbial
properties used in pharmaceutical preparations including oral liquids, topicals and
parenteral preparations.
• PG is being associated with cardiovascular, hepatic, respiratory and CNS
adverse events, especially in neonates where the biological half-life is prolonged
(~17h) compared with adults (5h).
• If parentral preparation containing PG must be infused slowly.
• PG has laxative action at high oral doses through high osmotic pressure
effects.[8,9,19,20,21]
7
“flushing out” umbilical catheters with solutions containing benzyl alcohol,
because of trace levels of Benzaldehyde that were present; Dilution of
nebulisation solutions with benzyl alcohol-preserved saline led to severe
respiratory complications and even death in neonates. Attributed to accumulation
of BA due to an immature metabolic capability. Only dilute inhaled solutions with
non-preserved, sterile diluents.[8, 9, 20, 21, 22]
Sodium Benzoate toxicity
Widely used as a preservative in cosmetics, foods and pharmaceuticals (including
injectable and oral liquids). Injectable combinations of Sodium Benzoate and
Caffeine should not be used in neonates, found to elicit non-immunological
contact reactions, including urticarial and atopic dermatitis; Limitation on dosing
of sodium benzoate to neonates ≤10mg/kg/day due to immature metabolic
capability.[8, 9, 20, 21, 22, 23]
Ethanol Toxicity
Thimerosal toxicity
Widely used as a co-solvent to aid solubility; In USA, maximum use in the
following measure:
• <0.5% for children under 6-years
• <5% for children 6-12-years
• <10% for children over 12-years
Acute (overdose) or chronic (long-term use) toxicity is possible; May cause
adverse symptoms of intoxication, lethargy, stupor, coma, respiratory depression
and cardiovascular collapse[8,9,20,21]
Peanut Oil Toxicity
Peanut oil is used as a food additive and as a solvent in intra-muscular
injections.[8,9]
It has been suggested that the use of peanut oil in childhood (infant formula and
topical preparations) can lead to later episodes of hypersensitivity, and therefore
should be discontinued.[8,9,20,21]
Anti-microbial Preservatives
Benzyl Alcohol toxicity in neonates, so widely used as a preservative in
cosmetics, foods and pharmaceuticals (including injectable and oral liquids);
Toxic syndrome observed in neonates – it was attributed to the practice of
Used as a preservative in cosmetics, in soft contact lens solutions and
pharmaceuticals (primarily vaccines). Being phased out from most paediatric
vaccines as better options emerge, possible links with toxicity in paediatric
vaccines, e.g. childhood autism, have been discounted after much debate. [6, 8, 9,
23]
Propellants
A topical aerosol made up of two components i.e., product concentrate and
propellant. A propellant is a chemical with a vapour pressure greater than
atmospheric pressure at 40°C (105°F).[12] Propellants commonly used in
pharmaceutical aerosols are
include chlorofluorocarbons (CFCs),
hydrocarbons(HCs),
hydro-chlorofluorocarbons(HCFCs)
and
hydrofluorocarbons(HFCs), and compressed gases.
Hydrocarbons are generally widely accepted as it Low Relative Cost, have best
Stability and Purity property as well as the fulfilling the following criteria in
range for accepting it; they are low odour, range of boiling points, wide range of
vapour pressures, low toxicity, versatility and efficiency, natural compounds,
flammability, echo friendly.[9, 12, 23, 24, 26, 27, 28]
Various propellants used in pharmaceutical aerosol and its properties
Table 3. Various propellants used in pharmaceutical aerosol and its properties:
Code
V.P. (psia)
700F
B.P.
(°F at 1 atm.)
Density (g/ml)
70 0F
I. Chloroflurocarbon propellants:
Trichloromonofluoromethane
CCl3F
Dichlorodifluoromethan
CCl2F2
11
12
13.4
84.9
74.7
-21.6
1.485
1.325
Dichlorotetrafluoroethane
114
Name of Chemicals
Empirical Formula
CClF2ClF2
Water solubility
1.1 g/L (at 680F)13
280 mg/L (at 770F)14
130 mg/L (at 770F)14
0.01%15, 16
27.6
39.4
1.468
II. Hydrochlorofluorocarbon and Hydrofluorocarbon Propellants:
Chlorodifluoromethane
CHClF2
22
-135.7
-41.4
1.21
Trifloromonofluoroethane
CF3CH2F
134a
85.8
-15.0
1.21
Chlorodifluoroethane
CH3CClF2
142b
43.8
14.4
1.12
Difluoroethane
CH3CHF2
152a
43.8
-12.5
0.91
Heptafluoropropane
III. Hydrocarbon Propellants:
Propane
Isobutene
Butane
Pentane
IV. Compressed Gases:
CF3CHFCF3
227
27.7
2.3
1.41
2770 mg/L (at 770F)14
1.0 wt.% @ 70°F,
autogeneous pressure
1,400 mg/L (at 770F)14
1.7 wt.% @ 70°F,
autogeneous pressure
108 mg/L (at 770F)14
C3H8
C4H10
C4H10
C5H12
A-108
A-31
A-17
124.7
45.1
31.2
-6.2
-43.7
10.9
31.1
-
0.50 @ 68 0F (g/ml)
0.56 @ 68 0F (g/ml)
0.58 @ 68 0F (g/ml)
0.63
62.4 ppm (at 770F)14
263 mg/l (at 770F)14
61.2 mg/L (at 770F)14
38 mg/L (at 770F)14
Nitrogen
N2
NA
492
-320
0.97
Nitrous oxide
Carbon dioxide
N2O
CO2
NA
NA
735
852
Compressed air
Mixture of N2 and O2
NA
NA
-127
-109
-297.4 0F (O2)
-384.8 0F (N2)
1.53
1.53
1 (O2) 0 (N2)
Linda safety data
0.015 @ 770F or
1.81X10+4 mg/L (at 69.80F)14
0.588 @ 770F
0.759 @ 770F
39 mg/l (O2)
20 mg/l (N2).
*NB: Hydrocarbon blends are also used as propellant e.g.:
• A-46 =15.2% Propane / 84.8% Isobutane
• NP-46 = 25.9% Propane / 74.1% N-butane
Innovat International Journal Of Medical & Pharmaceutical Sciences Vol 1 Issue 1 Nov-Dec 2016
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Mahendra Pratap Swain et.al
8
• NIP-46 = 21.9% Propane / 31.3% Isobutane /46.8% N-Butane As like this many blends are also used in aerosol formulation. Various examples of blends are A-31, P31, NIP-31, A-70, NP-70, NIP-70, A-85, NP-85, A-108. 25, 26, 27, 28
10. Committee of experts on the transport of dangerous goods and on the
Abbreviation
globally harmonized system of classification and labelling of
Active Pharmaceutical Ingredients
APIs
chemicals. From web www.google.com.
New Drug Delivery System
NDDS
11. F. Chen, Toxicology and Cellular Effect of Manufactured
Metered Dose Inhalers
MDIs
Nanomaterials US patent 20,120,315,218 A9, 2012
Dry Powder Inhalers
DPIs
12. D. D. Roberts, P. D. R. Soto, Methods for modulating
Chronic Obstructive Pulmonary Disease
COPD
chemotherapeutic cytotoxicity WO 2,014,160,183 A1, 2014
Liquefied Gases
LGs
13. Web: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401168/
Oro-Dispersible Tablets
ODTs
14. Physiological Aspects of Compatibility and Incompatibility in Grafted
Absorption, Distribution, Metabolism And Excretion
ADME
Cucumber Seedlings, Journal of the American Society for
Finished Pharmaceutical Products
FPPs
Horticultural Science, 2011
Propylene Glycol
PG
15. Ultraviolet and visible spectroscopy, 2008, 2nd ed.
Chlorofluorocarbons
CFCs
16. Web:
http://www.tandfonline.com/doi/pdf/10.1081/E-EPT3Hydrocarbons
HCs
100000466
Hydro-chlorofluorocarbons
HCFC
17. I. P. b. Sousa, A. B. Schnürch,Presystemic metabolism of orally
administered drugs and strategies to overcome it, sciencedirect,Journal
Hydro-fluorocarbons
HFCs
of Controlled Release Volume 192, 28 October 2014, Pages 301–309
18. Pharmaceutical inhalation aerosol technology, 2015,2nd ed.
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