Contents
Surfactants, CMC, Emulsions and Foams

Surface Tension of Inhalation Formulations: Pendant Drop Checks for Aerosol, Nebulizer and Inhaler Liquids, and Pulmonary Surfactant Mechanics

Surface tension is one of the liquid properties that shapes how an inhalation formulation breaks into droplets in a nebulizer, nasal spray or spray dryer. Measure it by pendant drop at the formulation bench, alongside viscosity and droplet size testing, so excipient and surfactant changes are seen before device tests.

Who this is for: Formulation scientists and CDMOs developing nebulizer solutions, nasal sprays, soft mist liquids and spray drying feeds for dry powder inhalers, and pulmonary surfactant researchers.

Where it fits: Excipient and surfactant screening, batch comparison of liquid formulations, and spray drying feed checks before droplet size and device testing.

What it does not do: It does not measure droplet size, aerodynamic diameter or delivered dose, and it is not a lung function or clinical test.

Method
Pendant drop surface tension, equilibrium and over drop age, with Young Laplace fitting
Standard
Supports formulation characterization; droplet size is tested by laser diffraction or cascade impaction under FDA and USP methods
Setup
About 2 minutes
Abhimanyu Photo
Written by
Abhimanyu Bhandankar
Holds an MBA from Schulich School of Business and a BE in IT. He joined Droplet Lab in July 2019 and now leads sales and marketing.
CEO at Droplet Lab
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Droplet-Lab logo
Technical Review by
Droplet Lab Team
Droplet Lab builds precision instruments and software for surface science measurement, specialising in contact angle analysis and surface tension characterisation. Used by researchers across materials science, pharmaceuticals, coatings, and advanced manufacturing, Droplet Lab's Dropometer has contributed to studies published in peer-reviewed journals including Advanced Functional Materials (Impact Factor 19). The team combines instrument engineering with deep domain knowledge in wettability science with a focus on practical accuracy.
Read More
Abhimanyu Photo
Written By

Abhimanyu Bhandankar

CEO at Droplet Lab

Holds an MBA from Schulich School of Business and a BE in IT. He joined Droplet Lab in July 2019 and now leads sales and marketing.

Droplet-Lab logo
Reviewed By

Droplet Lab Team

Droplet Lab builds precision instruments and software for surface science measurement, specialising in contact angle analysis and surface tension characterisation. Used by researchers across materials science, pharmaceuticals, coatings, and advanced manufacturing, Droplet Lab's Dropometer has contributed to studies published in peer-reviewed journals including Advanced Functional Materials (Impact Factor 19). The team combines instrument engineering with deep domain knowledge in wettability science with a focus on practical accuracy.

Why it matters

Why surface tension matters for inhaled medications

363 million

people were affected by asthma in 2023, one of several respiratory diseases treated with inhaled medications.

World Health Organization, asthma fact sheet

70 to under 1 mN/m

is the range lung surfactant spans: the surface tension of water near body temperature is about 70 mN/m, and clinical surfactants reached minimum values below 1 mN/m on compression.

Possmayer et al., Chem. Rev. 2023; Xu, Li and Zuo, Am J Physiol Lung, 2023

Surface tension named

by FDA among formulation characteristics, with viscosity, density and rheology, that matter when choosing the container closure for nasal and inhalation sprays.

FDA guidance, nasal spray and inhalation solution, suspension and spray drug products, 2002

Sources: World Health Organization, Asthma fact sheet; Possmayer F. et al., Pulmonary surfactant: a mighty thin film, Chemical Reviews, 2023; Xu X., Li G., Zuo Y.Y., American Journal of Physiology Lung Cellular and Molecular Physiology, 2023; US FDA, Nasal spray and inhalation solution, suspension, and spray drug products: chemistry, manufacturing, and controls documentation, 2002. Figures come from these sources, not from Droplet Lab measurements.

Quick reference

What this inhalation formulation check does and what it does not

A quick reference for inhalation formulation teams checking fit before reading further.

Evidence Box

Problem this solves

Excipient, surfactant or concentration changes that shift a formulation's surface tension, seen only later in droplet size or spray dried particle results.

Standards

FDA guidance names surface tension among formulation characteristics for nasal and inhalation sprays; droplet size itself is tested by laser diffraction or cascade impaction.

Peer reviewed method

The Dropometer drop shape method was validated against a KRUSS DSA100E in two peer reviewed papers, in Review of Scientific Instruments and Colloids and Surfaces A.

Customer case study

A pharmaceutical CDMO measures surface tension at the formulation bench to steer spray dried droplet and particle size, measuring in house within about ten weeks of first enquiry.

Published research

Pulmonary surfactant researchers use drop shape methods such as constrained drop surfactometry to measure surface tensions from about 70 down to below 1 mN/m.

Honest limit

Surface tension is one of several drivers of droplet size. Viscosity, density and the device matter as much.

Who this is for

What inhalation formulation question are you trying to answer?

Pick the card closest to your role. Each one points to the part of this page that answers it.

Formulation scientist

You develop nebulizer solutions and suspensions, nasal sprays or soft mist liquids, and change surfactants, salts, saline strength or cosolvents. Surface tension at each step shows how much the liquid changed before you run droplet size tests.

Measure viscosity and density too; surface tension alone does not set droplet size.

Spray drying or CDMO team

You make spray dried powders for a dry powder inhaler, with or without a carrier, or other particulate products. Feed surface tension tracks how excipient and surfactant changes will shift atomized droplet size, particle size and surface area, as one CDMO does.

Measure the feed at its spray temperature and concentration.

Pulmonary surfactant researcher

You study lung surfactant biophysics, surfactant preparations or their aerosol delivery. Pendant drop gives equilibrium and adsorption surface tension at the bench; compression cycling needs a dedicated surfactometer.

Pendant drop does not reproduce breathing cycles.
Fit check

Is this the right check for your inhalation work?

It measures the surface tension of the liquid. It does not measure the aerosol.

Good fit if

You compare surfactants, excipients or concentrations in a liquid formulation.
You check spray drying feeds before atomization.
You compare batches or suppliers of a nebulizer or nasal formulation.
You measure adsorption of surfactant preparations over drop age.
You need small sample volumes of costly drug substance.

Less relevant if

You need droplet size distribution or aerodynamic diameter.
You need delivered dose or aerosol output.
You need surface tension under breathing like compression cycles.
You test dry powders directly, not liquids.
Summary

How surface tension supports inhalation formulation work

The answer in under a minute.

Measure the surface tension of each liquid inhalation formulation or spray drying feed by pendant drop, at a fixed drop age and temperature. It shows how excipient and surfactant changes alter the liquid that the nebulizer, spray or atomizer must break up. Confirm the effect with droplet size testing.

The Dropometer pendant drop tensiometer runs the measurement. Our pendant drop method entry and surface tension measurement guide explain the method. A pharmaceutical CDMO uses it to steer spray dried particle size, and our pharmaceutical guide covers wider formulation work.

The problem

Why surface tension matters in pulmonary drug delivery

Inhaled medicine for asthma, obstructive lung disease, cystic fibrosis and respiratory infection depends on pulmonary drug delivery: making droplets or particles of the right size, so that inhaled medications deposit within the lungs rather than in the mouthpiece, throat or trachea. Patients inhale the aerosol, and aerosol penetration from the central airways to the small airways and peripheral lung depends on the size of the particles delivered; the airway surface liquid and mucus then govern clearance and absorption. Nebulizers, nasal sprays, soft mist inhalers and spray dryers all start with a liquid, and how that liquid breaks into droplets depends on its surface tension, viscosity and density as well as the device. FDA guidance for nasal and inhalation sprays names surface tension among the formulation characteristics that matter, and droplet size distribution is tested by laser diffraction or cascade impaction. Small formulation changes, a new surfactant, salt level or cosolvent, can shift surface tension and with it droplet formation, as one CDMO found for spray dried powders. The lung itself is a surface tension problem too. Pulmonary surfactant, a film of phospholipid and surfactant proteins, causes a decrease in alveolar surface tension from about 70 mN/m for water to very low values on compression. Surfactant preparations, many of bovine or porcine origin, are given by instillation to the preterm infant and studied as aerosolized therapy, and plasma proteins such as serum albumin can inhibit them. Teams need a quick, small volume surface tension measurement at the formulation bench, before slower droplet size and device tests.

Droplet size changes after an excipient or surfactant change.
Spray dried particle size drifts between feed batches.
Nebulizer output or droplet size differs between batches of one formulation.
A new supplier's surfactant behaves differently in the formulation.
Surface tension readings drift during measurement.
Troubleshooting

Why inhalation formulation results shift and what to check

Why:

  • Surfactants and some excipients lower surface tension, which changes how the liquid breaks into droplets.

How to detect:

  • Surface tension differs between old and new formulations at the same drop age.

Corrective action:

Measure surface tension against concentration, and check droplet size on the shortlist. Our CMC assessment page covers surfactant curves.

Why:

  • Surfactants take time to reach a fresh surface, so atomization sees a higher dynamic surface tension than equilibrium.

How to detect:

  • The reading keeps falling over seconds to minutes.

Corrective action:

  • Record surface tension over drop age and compare early and late values.

Why:

  • Viscosity and density also drive droplet size, sometimes more than surface tension.

How to detect:

  • Droplet size changes while surface tension stays the same.

Corrective action:

  • Measure viscosity and density with every formulation change.

Why:

  • Nebulizer type, mesh condition and spray actuation change droplet size directly.

How to detect:

  • The same formulation gives different droplet sizes on different devices.

Corrective action:

  • Test formulations on one device, and treat device changes separately.

Why:

  • Surface tension falls as temperature rises, and spray drying feeds may be heated.

How to detect:

  • Readings vary with room or feed temperature.

Corrective action:

  • Measure at a fixed temperature close to use conditions.

Why:

Drop age, density values and contamination change readings. Our guide to reproducible surface tension measurement covers fair comparisons.

How to detect:

  • A reference liquid reads differently between sessions.

Corrective action:

  • Write the method down and measure water or a reference solution each session.

Not sure surface tension explains your droplet size change?

Send two formulations and their droplet size data, and we will look at them with you on a call.

Lab records

What an inhalation formulation surface tension record contains

Each measurement produces a record you can file with the formulation batch, beside viscosity and droplet size results. It can feed into your existing development records.

Formulation and batch

Formulation version, batch, surfactant and excipient levels, and saline or buffer strength.

Method settings

Temperature, density, drop age at reading and number of drops.

Readings

Surface tension per drop, the median and spread, and the curve over drop age.

Linked tests

Viscosity, density and droplet size or particle size results for the same batch.

Decision

Proceed to device testing, adjust the formulation, or investigate.

Drop images

Automatic edge and baseline detection gives the same reading from the same image, so a reviewer can recheck any result.

Measurements

What to measure on an inhalation formulation

Equilibrium

Surface tension at a fixed drop age

Why it matters: It compares how much each formulation lowers surface tension.

How to interpret: Compare with the previous formulation and with water or saline measured the same way.

When it is not enough: It does not predict droplet size on its own.

Dynamic

Surface tension over drop age

Why it matters: Atomization creates fresh surface in milliseconds, before surfactants fully adsorb.

How to interpret: A slow fall suggests the spray sees a higher tension than the equilibrium value.

When it is not enough: Pendant drop cannot reach millisecond surface ages.

Concentration

Surface tension against surfactant concentration

Why it matters: It shows where extra surfactant stops lowering surface tension.

How to interpret: Use the curve to set surfactant levels with a margin.

When it is not enough: It does not show effects on drug stability.

Companion

Viscosity, density and droplet size

Why it matters: Together with surface tension they explain droplet formation.

How to interpret: Change one property at a time where you can.

When it is not enough: Device tests remain the final check.

Validation

Validated measurement approach for formulation surface tension

How the Dropometer itself has been validated, and where pharmaceutical teams have used it.

Peer reviewed method

The Dropometer drop shape method is published in Review of Scientific Instruments and Colloids and Surfaces A. Contact angle was validated against a KRUSS DSA100E, with a published accuracy of 0.35°.

See the validation papers

Customer evidence in spray dried formulation

A pharmaceutical contract development and manufacturing organisation turns client drug substances into solutions and spray dried powders. Its scientists found small excipient changes shift a formulation's surface tension and with it the droplet and particle size from the spray dryer. In 2025 they added a Dropometer and were measuring in house within about ten weeks.

Read the case study
QC Protocol

How to measure surface tension of inhalation formulations

Six steps per formulation. Repeat for each excipient, surfactant or concentration change.

1

Lock the method

Fix temperature, drop volume, drop age at reading and the number of drops for each formulation type.

3

Measure the formulation

Form a pendant drop of the formulation from a clean capillary needle and record surface tension over drop age.

4

Repeat and record

Repeat the set number of drops and record the median at the locked drop age.

5

Compare versions

Compare with the previous formulation, and assess it in combination with viscosity and density for the same batch.

We completed our gage R&R study on the unit and it performed very well.

Brandon Barbee

Corporate Quality Engineer, Zeus Industries, Polymer Manufacturing

Download the inhalation formulation surface tension SOP

A two page SOP you can adapt for your formulations, with the method lock, drop age, reference checks, a troubleshooting table and a record sheet.

Pendant drop surface tension measurement with the Dropometer

Pendant drop surface tension measurement with the Dropometer

Example output

Example surface tension log for nebulizer formulation versions

Example data only. Your values will differ and must be confirmed with your own droplet size testing.

How to read this log

Adding surfactant lowered surface tension; version C lowered it most but kept falling with drop age, so the spray may see a higher value than the equilibrium reading. The droplet size column comes from laser diffraction on the same batches, not from the tensiometer.

Example inhalation formulation surface tension log

Version Change Surface tension at 5 s (mN/m) Surface tension at 120 s (mN/m) Droplet size change Decision
Reference Saline only 72 72 Reference Reference
A Low surfactant 58 52 Small Keep
B Medium surfactant 50 44 Moderate Keep
C High surfactant 54 36 Larger than expected Investigate
D Cosolvent added 61 60 Small Keep

Example data, not customer data. Saline based formulations at 25 °C; median of 3 drops; early value at 5 s, equilibrium at 120 s.

Signal order

The order to check signals on a formulation

Check these in order. Each one rules out a cause before you look at the next.

1

Method and reference

Rules out temperature, density and contamination errors.

2

Equilibrium surface tension

Shows how much the formulation changed.

3

Curve over drop age

Shows how fast surfactants adsorb.

4

Viscosity and density

Rules out the other liquid drivers of droplet size.

FAQ

Common questions about surface tension in inhaled medications

Questions inhalation formulation teams ask about surface tension.

It is one of the drivers, with viscosity, density and the nebulizer itself. Lower surface tension usually makes a liquid easier to break into droplets, but the size you get also depends on the device and its settings. Measure surface tension as part of the formulation picture, and confirm droplet size by laser diffraction or cascade impaction.

FDA guidance for nasal spray and inhalation solution, suspension and spray products lists surface tension among formulation characteristics, with viscosity, density and rheology, relevant to the container closure system. Droplet size distribution and aerodynamic size are tested separately. Surface tension is a development tool here, not a release test on its own.

The mechanism is simple: sprays and nebulizers create fresh surface very quickly, before surfactants fully adsorb, and this adsorption phenomenon takes time. A formulation that reaches low surface tension only after a minute may behave like a higher tension liquid during atomization. Pendant drop shows the trend from seconds onward; faster methods are needed for millisecond surface ages.

For equilibrium and adsorption surface tension, yes. Surfactant preparations adsorb to about 22 to 25 mN/m at equilibrium, Zuo reported. The very low values, below 5 mN/m, appear only under compression cycling, which needs a dedicated captive bubble or constrained drop surfactometer rather than a pendant drop tensiometer.

The feed's surface tension affects how the atomizer forms droplets, which sets particle size and shape. A pharmaceutical CDMO measures feed surface tension at the formulation bench to steer particle size before spray drying runs. Measure at the feed temperature and solids content you will spray.

Only a single pendant drop per reading, tens of microlitres, plus enough for repeats. That suits early formulation work with costly drug substance. Clean the needle between formulations so surfactant carry over does not lower the next reading.

Yes. A surface tension curve against concentration shows where surfactant stops lowering surface tension, the critical micelle concentration. Our page on the FDA 510(k) surface tension appendix describes how FDA uses such curves for contact lens care products, a different product class.

A pendant drop tensiometer with temperature control and drop age tracking. The Dropometer does this at the bench with small volumes. Our production QC buying guide compares options, and our surfactants and emulsions hub covers related formulation pages.

Business impact

What changes when you measure formulation surface tension

Typical changes in how teams work. Benchmarks are given only where a published source exists.

Before and with formulation surface tension checks

Metric Before Dropometer With Dropometer Indicative Benchmark
Formulation screening Droplet size test for every version Surface tension first, device tests on the shortlist No published benchmark; track on your own projects
Spray drying feeds Particle size seen after the run Feed surface tension checked before the run CDMO in house measurements within about ten weeks of enquiry (case study)
Regulatory dossier Surface tension not recorded Surface tension recorded with viscosity and density Named among formulation characteristics in FDA nasal and inhalation guidance (2002)
Sample use Large volumes for device tests Single drops for screening No published benchmark; track on your own lab

See the measurement on your own formulations

Send two formulation versions. We will show the comparison on a call.

Estimate saved formulation screening work

Enter your own numbers. The result is an estimate, not a Droplet Lab claim.

Inhalation formulation screening estimate

Estimate saved formulation screening work.

Each Dropometer unit is US$5,000; the default models one unit.
Your own cost to run droplet size or device tests on one version.
Formulation preparation, droplet size testing and analysis.
No published benchmark. Use your own estimate and start low if unsure.

Result

~0
Candidates saved per month
~0
Monthly savings
~0
Payback period
~0
First year net benefit

Monthly savings = materials saved + technician time saved from reduced iterations.

Limits

What surface tension cannot tell you about an inhaled medication

Honest limits, so you know when to reach for another test.

Surface tension does not set droplet size on its own.
Pendant drop cannot reach millisecond surface ages.
It does not reproduce breathing compression cycles.
It measures liquids, not dry powders.
Temperature and drop age must be locked.
It makes no claim about therapeutic effect.

Pendant drop surface tension describes the liquid before it is atomized. Droplet size, aerodynamic diameter, delivered dose, deposition, which is measured by imaging and clinical studies, and any clinical effect or efficacy need their own tests.

How this page was created

Editorial and technical transparency notes for this page.

Transparency Details 4 checklist items
01

Drafting assistance

Drafted with Claude Opus 5.5 (Anthropic) using web search for sources, then edited by the Droplet Lab team.

02

Technical review

Reviewed and edited for technical accuracy by the Droplet Lab Team.

03

Verification steps

Standard identifiers, units, thresholds and key procedural claims are checked against cited sources before publication.

04

Updates

Reviewed every 12 months or when the underlying method changes.

Report a correction

Spotted an issue in this summary? Send a correction request and our team will review it.

Correction Request

We work hard to keep this page accurate and up to date. If you spot an error (wrong revision/year, missing requirement, incorrect interpretation, or broken link), tell us and we'll review it.

Contact us to report a correction
Sources

References

1.
World Health Organization. Asthma fact sheet. https://www.who.int/news-room/fact-sheets/detail/asthma
2.
World Health Organization. Chronic obstructive pulmonary disease (COPD) fact sheet. https://www.who.int/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease-(copd)
3.
Possmayer, F., Zuo, Y.Y., Veldhuizen, R.A.W., Petersen, N.O. Pulmonary surfactant: a mighty thin film. Chemical Reviews 123:13209 to 13290, 2023. https://doi.org/10.1021/acs.chemrev.3c00146
4.
Zuo, Y.Y. Comparative biophysical study of clinical surfactants using constrained drop surfactometry. American Journal of Physiology Lung Cellular and Molecular Physiology 327:L535 to L546, 2024. https://doi.org/10.1152/ajplung.00058.2024
5.
Xu, X., Li, G., Zuo, Y.Y. American Journal of Physiology Lung Cellular and Molecular Physiology 325:L508 to L517, 2023. https://doi.org/10.1152/ajplung.00101.2023
6.
US FDA. Nasal spray and inhalation solution, suspension, and spray drug products: chemistry, manufacturing, and controls documentation. Guidance for industry, 2002. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/nasal-spray-and-inhalation-solution-suspension-and-spray-drug-products-chemistry-manufacturing-and
7.
US FDA. Metered dose inhaler (MDI) and dry powder inhaler (DPI) drug products: quality considerations. Draft guidance, 2018. https://www.hhs.gov/guidance/sites/default/files/hhs-guidance-documents/FDA/15087-dft.pdf
8.
USP chapter 1601. Products for nebulization: characterization tests. https://doi.usp.org/USPNF/USPNF_M4347_03_01.html
9.
USP chapter 601. Inhalation and nasal drug products: aerosols, sprays, and powders, performance quality tests. https://doi.usp.org/USPNF/USPNF_M99360_06_01.html
10.
Van Strien, J. et al. Spray characteristics from nasal spray atomization. arXiv:2205.01827, 2022. https://arxiv.org/abs/2205.01827
11.
Chen, X. et al. Contact angle measurement with a smartphone. Review of Scientific Instruments 89(3):035117, 2018. https://pubs.aip.org/aip/rsi/article-abstract/89/3/035117/368179/Contact-angle-measurement-with-a-smartphone
12.
Surface tension measurement with a smartphone using a pendant drop. Colloids and Surfaces A: Physicochemical and Engineering Aspects. https://www.sciencedirect.com/science/article/abs/pii/S0927775717307744