Solution Preparation is a key aspect in the field of Pharmaceutical Analytical Laboratory (Quality Control). Because the Solution preparation will decide the accurate results.

Preparation of Solutions
Solution Preparation
Image Courtesy Canva Pro

Techniques for Solution Preparation

Based on the sample solution preparation and types of Solutions, a list of procedures is provided below for easy reference.

Weight/ Volume sample solution (Solid in liquid, solute)

Refer below procedure to prepare a solid sample solution.

Weigh and transfer the required quantity into a suitable receiver. If the material is transferred to a flask, add a diluent of suitable volume while holding and rotating the flask. Ensure the flask is in a slant position so that the material stuck to the stem will wash down into the flask. Swirl to dissolve and dilute up to the mark with the help of a Pasteur pipette. Place the stopper and shake well or sonicate the contents to dissolve.

Important Notes for Wt/Vol Solution Preparation

  • Do not keep the stopper and shake the flask, before making up the volume to the mark with diluent to dissolve the material.
  • Final Volume makeup shall perform once after the flask and solution attain room temperature.
  • While final volume make up, use a clean and dry Pasteur pipette or dropper.

Volume/ Volume sample solution (Liquid in liquid, sample)

Refer below procedure to prepare a liquid sample solution preparation (Volume/ Volume sample solution).

Weigh the required quantity with the help of a Pasteur pipette or microsyringe into a suitable receiver (Volumetric flask, conical flask, beaker, etc.,) as described above. Transfer the required quantity into a suitable receiver.

Ensure to transfer diluent of suitable volume once after measurement of the material. Hold and rotate the flask in a slant position so that the material if any, stuck to the stem will wash down into the flask.

Swirl to dissolve and dilute up to the mark with the help of a Pasteur pipette. Place the stopper and shake well or sonicate the contents to dissolve.

Important Notes for Vol/Vol Solution Preparation

  • Do not keep the stopper and shake the flask before making up the volume to the mark with diluent to dissolve the material. The final Volume shall make up once the flask and solution attain room temperature. Use a dry pipette or dropper for final make-up.

Solution Preparation and Key measures

It is important that the below operations are part of the Sample solution preparation procedure. Hence, refer below to ensure accurate preparation of sample solutions.

Sonication with Ultrasonicator

Sonication is a very important unit operation for sample preparation. Ultrasonicator / Ultrasonic bath equipment can be sued for this operation.

Monitor the Temperature consistently with an external digital thermometer or inbuilt thermometer because products that are temperature sensitive may degrade at higher temperatures and have less extraction at low temperatures. Maintaining the temperature of the sonicator is a critical step for analysis.

During sonication maintain the temperature up to 20 to 25°C unless otherwise specified in the respective test procedure.

The water level of the sonicator should be optimum if it will be more flask will float and the chance of falling down, if it will be the less effective dissolution of the sample.

Intermediate shaking of solution during the entire duration of sonication is important for the effective dissolution of the sample in a solvent, in case of no or less intermediate shaking, will cause lumps and poor dissolution which will cause erratic results.

Place the glassware in the basket while sonication. Do not place the glassware directly at the surface of the sonicator.

Do not load excess ice during sonication which leads to insufficient sonication and reverses chemical reactions, always used cold water to maintain temperature.

Ensure there is no adherence or powder sticking in the sides of volumetric flasks and lump formation while sonication.

After completion of sonication, wait for a few minutes to make up until the solution attains room temperature to avoid any variations in results.

Use an ear plug while performing sonication.

After weighing the powder into the volumetric flask, fill the flask up to 50% with diluent and swirl to disperse the powder completely before keeping it for sonication to avoid any lump formation.

The pipetting technique (Dilutions, liquid in liquid, volume/volume)

Take the required volume of solution with the help of clean and dry pipettes.

Wipe off the tip of the pipette with tissue paper that is adhered to the outer surface of the pipette.

Place the tip of the pipette on the inner side of the receiver (e.g. flask) and transfer slowly.

Hold the pipette in the same position for 10-15 seconds so as to ensure the liquid was transferred completely and no adherence of liquid was found to the inner walls of the pipette.

Preparation of Solutions – Liquid Viscosity

Since the pipette was originally factory-calibrated using water, any liquid that has a viscosity higher or lower than water will impact the volume dispensed. Viscosity differentials should be accounted for and taken into consideration in order to enhance the accuracy of the instrument.

Note: Never blow the bulb for transferring residual liquid from the pipette to the receiver.

Make-up Volume – Solution Preparation

The makeup of the Volume is a Critical parameter in Solution Preparation.

  1. Volume should be made up only after attaining room temperature,
  2. In the case of colorless liquid, consider the lower meniscus.
  3. In the case of colored liquid, consider the upper meniscus. 
  4. After volume make up assure that the solution should be uniform
  5.  During mixing up solution no spill should happen
  6. Before making further dilution allow settling down air bubbles generate during mixing.
  7. Avoid vigorous shaking for a short duration.
  8. Make sure Gentle shakes for a longer period.
  9. Avoid Spilling of Solution while mixing.

How to read a Meniscus during Preparation of Solutions

Meniscus in Lab Measurements: The mechanism is the curve seen at the top of a liquid in response to its container. The meniscus can be either concave or convex. A concave meniscus (e.g., water in glass) occurs when the molecule of the liquid are more strongly attracted to the container than to each other. A convex meniscus (e.g., mercury in glass) is produced when the molecules of the liquid are more strongly attracted o each other than to the container. In some cases, the meniscus appears flat (e.g., water in some plastics).

When you read a scale on the slide of a container with a meniscus such as a graduated cylinder or volumetric flask, it’s important that the measurement accounts for the meniscus. Measure so that the line you are reading is even with the center of the meniscus. For water and most liquids, this is the bottom of the meniscus. For mercury, take the measurement from the top of the meniscus. In either case, you are measuring based on the center of the meniscus.

Measure the meniscus at eye level from the center of the meniscus. In the case of water and most liquids, the meniscus is concave. Mercury produces a convex meniscus.

Filtration for Preparation of Solutions

Filtration is one of the important techniques in Solution Preparation based on the requirement.

Filtration of  Blank/ Standard/ Test solution

Blank: First rinse the syringe with diluent, discard the initial volume of diluent solution through a filter holder, collect the required volume & after filtration discards the membrane filter.

Standard solution: First rinse the syringe & filter holder with a standard solution, discard the initial volume of std. solution through a filter holder, collect the required volume & after filtration discards the membrane filter.

Test solution: First rinse the syringe & filter holder with the test solution, discard the initial volume of test solution through a filter holder, collect the required volume & after filtration discards the membrane filter.

Filtration and Degassing of Mobile Phase for Chromatography

Prepare buffer solution as per STP & mix with the solvents as mentioned in STP

While preparing the mobile phase, add solvents in the same sequence as mentioned in STP & mix thoroughly in the mobile phase bottle Filter the mobile phase through a 0.45-micron Nylon membrane filter or as suggested in STP.

The limit for pH adjustment for the mobile phase & buffers meant for its preparation is ± 0.02 until unless specified.

Degas the mobile phase for 10 minutes for volumes 1000, 2000, and 3000 mL in a sonicator applying vacuum & degas for 20 minutes for volume 5000 mL in a sonicator applying vacuum.

Ensure that proper water level & temperature is maintained during sonication.  Avoid over-sonication to avoid polymerization of some of the salts.

Read never before Pharma articles only at PharmaeliX Site Master File SOP 2023 Ghost Peaks in HPLC Effective Guidance 2023

Tablet Crushing procedure (Pallet Crushing)

In addition to the above Solution preparation techniques, the Tablet crushing procedure is provided for reference purposes.

Crushing is a very important unit operation applicable where mentioned for tablet and capsule pallets. Fine and uniform crushing must to get an accurate result.