Application Note | NEPHEL.O™
Measuring the solubility of pharmaceutical compounds using NEPHEL.O™
by Gloria Pinilla, Dimitria Camasão
Senior Application Specialists, Rheolution Inc.
SUMMARY
- Solubility of drug compounds determines their absorption, bioavailability, safety, and quality and therefore, this characterization is crucial for drug development and quality control.
- NEPHEL.O™ has been used as a tool to determine the dissolution profile of two different pharmaceutical compounds.
- Acetaminophen (paracetamol) showed to be more soluble in DMSO when compared to acetylsalicylic acid (aspirin).
INTRODUCTION
The solubility of solid pharmaceutical compounds is a critical factor that their bioavailability, effectiveness, safety, and quality. Solubility determines how quickly and efficiently a drug can dissolve and be absorbed into the body, which can affect its bioavailability, therapeutic efficacy, and potential side effects. Therefore, understanding solubility is a crucial step in drug development, formulation, and dosage selection, as well as for ensuring the quality of medications throughout their shelf life.
Laser nephelometry has been shown to be an effective technique for the measurement of solubility of solid drug compounds [1]. Nephelometry is the measurement of scattered light at 90° when a laser beam is directed through a solution that contains suspended particles. The more particulate there is in the solution, the greater the amount of scattered light. In this work, the NEPHEL.O™ instrument was used to characterize the solubility of two well-known pharmaceutical compounds: paracetamol and aspirin.
MATERIALS AND METHODS
Commercial acetylsalicylic acid (ASA) and acetaminophen tablets were ground until forming a powder. Drug powders were weighed, mixed with DMSO and left at 37 °C for at least 40 min. PBS was then slowly added under stirring, reaching a final proportion of 5% DMSO and 95% PBS. Five concentrations were prepared for each drug: 1000, 500, 250, 125, and 62.5 µg/mL. One vial per concentration and per drug was prepared with 10 mL and tested in the NEPHEL.O™ (previously calibrated with formazin standards – FTU) four times at different positions. The cartridges used for optical emission and reception were the Emitt.635 (wavelength of 635 nm) and Receiv.ViS (wavelength range of 400 nm to 1000 nm), respectively. Average results are expressed as mean ± standard deviation.
RESULTS AND DISCUSSION
Figure 1 displays nephelometric measurements of samples containing different concentrations of ASA (turquoise line) and acetaminophen (orange line). For both drugs, an increase in the drug concentration resulted in a linear increase in the turbidity of the solutions (R2>0.94). The increase in turbidity was considerably higher for ASA when compared to acetaminophen suggesting that the first is less soluble than the second. Drugs that have lower solubility tend to contain a higher concentration of particles in the solvent, leading to a more pronounced scattering of light when compared to drugs with higher solubility. This more pronounced scattering (and less uniform because of the many particles) is also related to the higher standard deviation of the measurements for the ASA when compared to the acetaminophen.

Figure 1: Nephelometric measurements of samples containing different concentrations of ASA (turquoise line) and acetaminophen (orange line).
CONCLUSIONS
NEPHEL.O™ was able to successfully capture changes in the solubility of pharmaceutical tablets. Acetaminophen demonstrated higher solubility in DMSO (5%) as indicated by the lower turbidity when compared to ASA.
PRESPECTIVES
- The NEPHEL.O™ can continuously measure a sample in real time providing information about dissolution or sedimentation kinetics.
- Collecting and saving nephelometric measurements can be easily done using the instrument’s tablet, providing the added benefit of being exportable as and when required.
- NEPHEL.O™ allows the use of different vials for performing the measurements which can avoid sampling manipulation.
- It is possible to use different wavelengths of light to the sample in the NEPHEL.O™ by changing the optical cartridge to adapt and complement the testing results.
- The NEPHEL.O™ instrument allows for a scalable testing platform, where multiple units can be connected to the same operating tablet.
$7,300 per system
REFERENCES
[1] Hoelke, B., Gieringer, S., Arlt, M., & Saal, C. (2009). Comparison of nephelometric, UV-spectroscopic, and HPLC methods for high-throughput determination of aqueous drug solubility in microtiter plates. Analytical chemistry, 81(8), 3165-3172.
INTRODUCTION
The solubility of solid pharmaceutical compounds is a critical factor that their bioavailability, effectiveness, safety, and quality. Solubility determines how quickly and efficiently a drug can dissolve and be absorbed into the body, which can affect its bioavailability, therapeutic efficacy, and potential side effects. Therefore, understanding solubility is a crucial step in drug development, formulation, and dosage selection, as well as for ensuring the quality of medications throughout their shelf life.
Laser nephelometry has been shown to be an effective technique for the measurement of solubility of solid drug compounds [1]. Nephelometry is the measurement of scattered light at 90° when a laser beam is directed through a solution that contains suspended particles. The more particulate there is in the solution, the greater the amount of scattered light. In this work, the NEPHEL.O™ instrument was used to characterize the solubility of two well-known pharmaceutical compounds: paracetamol and aspirin.
MATERIALS AND METHODS
Commercial acetylsalicylic acid (ASA) and acetaminophen tablets were ground until forming a powder. Drug powders were weighed, mixed with DMSO and left at 37 °C for at least 40 min. PBS was then slowly added under stirring, reaching a final proportion of 5% DMSO and 95% PBS. Five concentrations were prepared for each drug: 1000, 500, 250, 125, and 62.5 µg/mL. One vial per concentration and per drug was prepared with 10 mL and tested in the NEPHEL.O™ (previously calibrated with formazin standards – FTU) four times at different positions. The cartridges used for optical emission and reception were the Emitt.635 (wavelength of 635 nm) and Receiv.ViS (wavelength range of 400 nm to 1000 nm), respectively. Average results are expressed as mean ± standard deviation.
RESULTS AND DISCUSSION
Figure 1 displays nephelometric measurements of samples containing different concentrations of ASA (turquoise line) and acetaminophen (orange line). For both drugs, an increase in the drug concentration resulted in a linear increase in the turbidity of the solutions (R2>0.94). The increase in turbidity was considerably higher for ASA when compared to acetaminophen suggesting that the first is less soluble than the second. Drugs that have lower solubility tend to contain a higher concentration of particles in the solvent, leading to a more pronounced scattering of light when compared to drugs with higher solubility. This more pronounced scattering (and less uniform because of the many particles) is also related to the higher standard deviation of the measurements for the ASA when compared to the acetaminophen.

Figure 1: Nephelometric measurements of samples containing different concentrations of ASA (turquoise line) and acetaminophen (orange line).
CONCLUSIONS
NEPHEL.O™ was able to successfully capture changes in the solubility of pharmaceutical tablets. Acetaminophen demonstrated higher solubility in DMSO (5%) as indicated by the lower turbidity when compared to ASA.
PRESPECTIVES
- The NEPHEL.O™ can continuously measure a sample in real time providing information about dissolution or sedimentation kinetics.
- Collecting and saving nephelometric measurements can be easily done using the instrument’s tablet, providing the added benefit of being exportable as and when required.
- NEPHEL.O™ allows the use of different vials for performing the measurements which can avoid sampling manipulation.
- It is possible to use different wavelengths of light to the sample in the NEPHEL.O™ by changing the optical cartridge to adapt and complement the testing results.
- The NEPHEL.O™ instrument allows for a scalable testing platform, where multiple units can be connected to the same operating tablet.
$7,300 per system
REFERENCES
[1] Hoelke, B., Gieringer, S., Arlt, M., & Saal, C. (2009). Comparison of nephelometric, UV-spectroscopic, and HPLC methods for high-throughput determination of aqueous drug solubility in microtiter plates. Analytical chemistry, 81(8), 3165-3172.
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