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To develop innovative drug delivery methods the knowledge of a drug's physicochemical properties, namely its

ionization constants is essential. Ranolazine and Atenolol are two key drugs used in clinical practice to treat

The dissociation constant that is pKa, is an important parameter since it governs a substance's ionization profile

and aids in the prediction of drug behavior in pharmaceutical formulations. The pKa of a therapeutic molecule

is also critical for drug development since it influences its solubility, absorption, distribution, metabolism, and

elimination. In formulations, the vehicles are frequently adjusted to a specific pH to achieve a desired level of

ionization of the drug for solubility and stability.

Ranolazine is clinically utilized to treat chronic stable angina, and it decreases the number of times the chest

pain occurs. Relieving symptoms of angina can increase the ability to exercise and perform strenuous work.

antianginal relief for individuals with acute chronic angina who are taking regular Atenolol doses. There are no

long-term side effects after a year or two of medication.

Previous studies have reported pKa values for Ranolazine in the range of 7.5–7.7 using potentiometric titration

and UV spectroscopy

potentiometric methods

composition, ionic strength, temperature, and instrumentation. Moreover, comparative determination of pKa

Table No 01: INSTRUMENTAL SPECIFICATIONS:

Balance

Sartorius

About 6-8 aliquots of the buffer solutions were prepared. For preparations of these buffer procedure followed

was as per IP 1996. First, 13.60 gm of KH

PO

was taken in 500 ml volumetric flask, dissolve in small amount

of distilled water, then make volume up to 500 ml with same. It will give 0.2 M 500 ml KH

PO

and in the

similar pattern freshly prepare 100 ml 0.2 M NaOH. Now place 50 ml 0.2 M KH

add sufficient volume of 0.2 M NaOH then make volume 200 ml, so it will give 200 ml specific pH buffer

solution. Different volumes of 0.2 M NaOH and 0.2 M HCl were added to the potassium hypo Phosphate solution

measured separately at 272 nm for RAN and 225.6 nm for ATN in which each buffer was considered as blank

each time. The obtained absorbance was plotted in the calibration graphs with pH on the x-axis and absorbance

and ATN were calculated.

Now from half of maximum absorption is plotted in graph and the value of pH on X-axis directly gives the

value of pKa.

0.198=0.618x+0.0908

All statistical analyses were performed using Microsoft Excel. Data are expressed as mean ± SD. The relative

standard deviation (RSD) was calculated to assess reproducibility

Table 03 shows the mean ± SD absorbance values for Ranolazine and Atenolol at different pH levels. Low SD

Table No 03: pKa value determination for RAN and ATN:

0.396± 0.003

Ranolazine: y = 0.0168x + 0.0222 (R² = 0.973)

Atenolol: y = 0.0618x + 0.0908 (R² = 0.9888)

Graph 1: Calibration data of RAN and ATN for pKa value by Spectroscopy

Fig 1: Calibration curves for RAN

Fig 2: Calibration curves for ATN

- Minor fluctuations in buffer pH due to environmental CO₂ absorption.

- Variability in pipette volume delivery during buffer preparation.

- Slight instrument baseline drift during long measurement runs.

- Temperature changes affecting dissociation equilibria.

Despite these possible influences, the low RSD values and high R² from regression analysis indicate that the

method is precise and reproducible.

UV- spectrophotometry technique is very useful for determination of pKa value because it is less time consuming

and gives reproducible result than other techniques. This work concludes pKa value for RAN and ATN can be

precisely determined using UV- Spectrometer. The obtained results shows that the pka values obtained are near