ISSN 0974-3618
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0974-360X (Online)
RESEARCH ARTICLE
Determination of Saturated Solubility of
Naproxen using UV Visible Spectrophotometer
Lalit Kumar1, BS Suhas, Girish Pai K1, Ruchi
Verma*
Department of Pharmaceutical Chemistry,
Department of Pharmaceutics1, Manipal College of Pharmaceutical
Sciences, Manipal University, Madhav Nagar – 576 104, Manipal, Udupi,
Karnataka, India.
*Corresponding Author E-mail: ruchiverma_farma@yahoo.com
ABSTRACT:
Solubility of the drug plays a crucial
role in the formulation and development of the drug. Assessing the solubility
of the drug is one of the most important parameter in pre-formulation.
Parenteral formulations require sufficient solubility of the drug molecules.
Correspondingly bioavailability from solid formulations like tablets and
capsules is also dependent on solubility and permeability. The objective of
this study was to investigate the solubility of drug in different pH medium
using UV visible spectrophotometer. The drug solubility was studied in the pH
range 1.2 to 7.4. This study concludes that the naproxen has pH dependent
solubility.
KEY WORDS: Saturated Solubility, UV Visible
Spectrophotometer, Naproxen, pH range.
INTRODUCTION:
Solubility is one of the most critical preformulation properties which
play a significant impact on performance of a molecule. Solubility and
permeability are the two important properties of Biopharmaceutical
Classification System (BCS). Biopharmaceutical Classification System (BCS)
provides the scientific framework for designing of drug delivery systems and
many regulatory decisions. Solubility determination is one of the first most
important and extensively studies of preformulation. Aqueous solubility is a
solubility which effects on the bioavailability of the drug1,2.
Orally administered drug first gets dissolved in the gastrointestinal
milieu. Dissolved drug then permeates through the intestinal membrane and
reaches to the systemic circulation. As per the literature, about 40% of the drugs
molecules gets failed to meet this process because of non-optimal
biopharmaceutical properties like aqueous solubility1,2. Aim of the
present study is to determine the aqueous solubility of drug in different
dissolution medium.
EXPERIMENTAL:
Materials
The Naproxen was received as a gift sample
from Dr. Reddy’s Laboratories Ltd., Hyderabad, India. Potassium
dihydrogen phosphate, sodium hydroxide and hydrochloric acid were purchased
from Spectrochem Pvt. Ltd., Bangalore, India. The distilled water was produced in our research laboratory with
distillation unit.
Scanning of λmax of drug in different dissolution medium
The λmax of drug in
different dissolution medium (such as distilled water, pH 1.2, pH 5.8, pH 6.8, pH
7.4) was scanned using a UV Visible Spectrophotometer. In this study the stock
solution of naproxen was prepared in each medium. For a stock solution, 100 mg
of drug was taken in a 100 mL volumetric flask and dissolved in 1 mL of
methanol. Then the final volume was made up to the mark with a particular
solvent. Further the λmax of naproxen in all solutions was scanned
under spectrum mode in the wavelength range from 200 – 400 nm and
the peak table in all solutions was recorded.
Standard curve in different
medium
Standard curves of Naproxen have been carried out in different
dissolution medium (or solvents) such as distilled water, pH 1.2, pH 5.8, pH 6.8 and
pH 7.4. In this study the stock solution of drug was prepared in each medium.
For a stock solution, 100 mg of drug was taken in a volumetric flask and
dissolved in 1 mL of methanol. Then the final volume was made up to the mark
with a particular solvent. Further the dilutions were made using the same
dissolution medium to make different concentration solutions for standard
curve. The λmax of drug in each medium was scanned using UV
Visible Spectrophotometer3,4.
Saturated solubility study
The saturated solubility of the drug was determined in distilled water
and various buffers from pH 1.2 to 7.4. The 3 mL distilled water or buffer of required pH
were taken in 5 mL amber colored glass vials. An excess amount of drug was
added in each vials and closed with stopper. These glass vials were attached in
an orbital shaking water bath. The shaking was carried out for 48 hours with
the speed of 50 rpm and in the entire study the temperature was maintained
around 37 ± 0.5 °C. Then the resulting samples were filtered using syringe
filters with its pore size 0.22 µm. The filtrate were collected and after
suitable dilutions with the same solvent the absorbance of the drug was
analyzed with UV Visible Spectrophotometer (UV– 1601PC, Shimadzu Corporation,
Japan) at the pre-scanned λmax in particular solvent. Then the
absorbance was converted into concentration using standard curve of drug in
each concern solvent5-8.
RESULTS AND DISCUSSION:
Scanning of λmax
of drug in different dissolution medium
The scanned wavelengths (λmax) of drug in different
dissolution medium are given in the Fig. 1 to Fig. 5 and Table 1. As shown in
the results, wavelengths of drug in all dissolution medium are same which shows
pH of dissolution medium doesn’t effect on the wavelength of drug.
Table 1. The scanned drug λmax values in different
dissolution medium:
|
S. No.
|
Solvent used for study
|
Scanned drug λmax (nm)
|
|
1.
|
Distilled Water
|
272
|
|
2.
|
0.1N HCl (pH 1.2)
|
272
|
|
4.
|
Phosphate Buffer pH 5.8
|
272
|
|
5.
|
Phosphate Buffer pH 6.8
|
272
|
|
6.
|
Phosphate Buffer pH 7.4
|
272
|
Fig.1. UV drug scanning in Distilled Water
Fig.2. UV drug scanning in pH 1.2
Fig.3. UV drug scanning in pH 5.8
Fig.4. UV drug scanning in pH 6.8
Fig.5. UV drug scanning in pH 7.4
Standard Curve in
Different Medium
The standard curves in different aqueous medium are given below from
Fig.6 to 10 . The linear equation and co-efficient correlation (r2)
values of the standard curves in different medium are given in the Table 2. As
shown in the results, excellent correlation coefficients were obtained for drug
in all dissolution medium. This demonstrates a significant correlation between
the concentration of analyte and absorbance and hence the method is suitable
for analysis.
Fig.6. Standard Curve in Distilled Water
Fig.7. Standard Curve in 0.1N HCl
Fig.8. Standard Curve in pH 5.8
Fig.9. Standard Curve in pH 6.8
Fig.10. Standard Curve in pH 7.4
Saturated solubility
study
The data for the saturated solubility study are given in Fig. 11. The
solubility studies show that the drug is having pH dependent solubility as the
pH increases the drug solubility also increases. The present study indicates
the low solubility of drug in the distilled water whereas the solubility of drug
in pH 1.2 is extremely low. The solubility of drug in the distilled water is
even less than pH 5.8. This low solubility of drug in the lower pH range is due
to unionization of drug. Unionization of the drug can facilitate the
permeability of drug through the membrane, but drug solubility is the limiting
factor.
Fig.11. Saturated Solubility Studies of Naproxen
CONCLUSION:
Present research study concludes that the Naproxen has pH dependent
solubility which means the drug has low bioavailability in the stomach.
Saturated solubility study concludes that the low bioavailability of drug is
mainly due to low aqueous solubility. This study also suggests that there is a
need to improve the solubility of drug in the acidic medium and distilled
water.
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