Optimizacija pogojev in primerjava obarjanja natrijevega diklofenakata in dipiridamola iz njunih prenasičenih raztopin v prisotnosti polivinilpirolidona

Gorenc, Nejc (avtor), Bogataj, Marija (mentor)

Slaba topnost učinkovin predstavlja velik problem v razvoju farmacevtskih oblik. Eden izmed načinov izboljšanja topnosti slabo topnih učinkovin je uporaba dostavnih sistemov, ki temeljijo na prenasičenju učinkovin. Prenasičeno stanje, ki se tvori v prebavnem traktu po aplikaciji dostavnih sistemov je nestabilno, zaradi česar učinkovina stremi k obarjanju. V okviru magistrske naloge smo spremljali obarjanje dveh učinkovin iz njunih prenasičenih raztopin z ali brez prisotnosti različnih koncentracij zaviralca obarjanja polivinilpirolidona (PVP). Izbrani učinkovini sta bili natrijev diklofenakat (NaDF) in dipiridamol (DPL). Pripravili smo vzorce različnih koncentracij posamezne učinkovine in PVP v vodi (za NaDF) ali v 0,01 M HCl (za DPL). Obarjanje smo sprožili s spemembo pH medija, in sicer z dodatkom 1 mL 1 M HCl v 100 mL raztopine NaDF oziroma z dodatkom raztopine 0,4 M Na3PO4 v raztopino DPL do vrednosti pH 6,8. Po sprožitvi obarjanja smo s pomočjo potopne sonde z optičnimi vlakni oziroma s pomočjo analizatorja velikosti delcev določili koncentracijo raztopljene učinkovine oziroma velikost oborjenih delcev v različnih časovnih točkah. Metodi smo najprej izvajali ločeno, nato pa še sočasno v istem sistemu. Metodi sočasnega spremljanja obarjanja obeh učinkovin smo predhodno optimizirali. Povečali smo hitrost merjenja spektra iz 800 na 9600 nm/min in povečali korak merjenja iz 1 na 2 nm. Sonde v začetnih točkah nismo spirali, kar nam je omogočilo bolj pogosto merjenje in posledično boljši vpogled v obarjanje delcev, s tem pa smo tvegali lepljenje delcev na sondo in lahko tudi napačne meritve sonde. Glede na rezultate predvidevamo, da na obarjanje najverjetneje vpliva tako koncentracija učinkovine (stopnja prenasičenja), kot tudi koncentracija PVP oziroma razmerje med njima. Ugotovili smo, da višja koncentracija NaDF na obarjanje vpliva tako, da ga pospeši. Dodatek PVP je obarjanje v vseh poskusih zaviral. Rezultati merjenja velikosti delcev pri sočasnem in ločenem spremljanju obarjanja so bili zelo podobni, rezultati absorbanc pa so se razlikovali. Vzrok za to je bil ta, da smo pri obeh načinih merjenja (sočasno in ločeno) absorbanco merili pri različnih pogojih, velikost delcev pa pri enakih. Pri primerjavi istih razmerij koncentracije NaDF in PVP smo ugotovili, da je porazdelitev velikosti delcev primerljiva. Pri obeh učinkovinah smo v večini primerov opazili trend nastajanja večjih delcev iz manjših.

• Jezik: Slovenski jezik
• Ključne besede: obarjanje, prenasičenje, natrijev diklofenakat, dipiridamol, UV-Vis spektroskopija
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2019
• PID: 20.500.12556/RUL-112000
• Datum objave v RUL: 19.10.2019

GORENC, Nejc, 2019, Optimizacija pogojev in primerjava obarjanja natrijevega diklofenakata in dipiridamola iz njunih prenasičenih raztopin v prisotnosti polivinilpirolidona [na spletu]. Magistrsko delo. [Dostopano 6 maj 2025]. Pridobljeno s: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=slv&id=112000

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Optimization of precipitation conditions and comparison of diclofenac sodium and dipyridamole precipitation from their supersaturated solutions in the presence of polyvinylpyrrolidone

Izvleček

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.

• Ključne besede: precipitation, supersaturation, diclofenac sodium, dipyridamole, UV-Vis spectroscopy