Poor drug solubility is one of the biggest obstacles in the process of formulation development. One way to improve poor drug solubility is the use of supersaturating drug delivery systems. Supersaturation that takes place after the aplication of these delivery systems is a very unstable phenomenon thus the drug tends to precipitate. This thesis researches the precipitation of two drugs, namely diclofenac sodium (NaDF) and dipyridamole (DPL) from their supersaturated solutions in the absence and presence of different concentrations of the precipitation inhibitor polyvinylpyrrolidone (PVP).
We prepared samples of different concentrations of each drug and PVP in purified water for NaDF or 0,01 M HCl solution for DPL. To trigger the precipitation of NaDF we used 0,01 M HCl and in samples containing DPL we achieved the same effect by adding 0,4 M Na3PO4 to reach the pH value of 6,8. During the precipitation of our samples we used the fiber optic UV/Vis dip probe and the particle size analyzer to measure the concentration of the dissolved drug and the size of the precipitated particles in different time points, respectively. Both methods were first used separately and then simultaneously. For the purpose of simultaneous measuring, optimization of UV-Vis spectrophotometric measurement was performed by increasing the rate of spectrum measurement from 800 nm/min to 9600 nm/min and the measuring step from 1 nm to 2 nm. Also, at the beginning of the precipitation process, the dip probe was not cleaned between consecutive measurements. By doing this, we increased the risk of inaccurate measurements in favor of more frequent measurement.
According to the results, we assume that the drug concentration, the concentration of PVP and their ratio all have an important effect on drug precipitation. We discovered, that higher drug concentration accelerates its precipitation. Precipitation was slowed down with the addition of PVP. The results, obtained while measuring the size of the precipitated particles were the same regardless of the methods being used separately or simultaneously. However, the absorbance measured separately in a beaker and simultaneously with particle size differed greatly. We assume, that the main reason behind such behavior are different precipitation conditions in absorbance measurements of each method. Results of particle size distribution were comparable between different samples of the same drug/PVP concentration ratio. Results obtained from experiments performed on both drugs showed, that in most cases bigger particles were forming from smaller particles over time.
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