Sočasno spremljanje procesov obarjanja zdravilnih učinkovin iz prenasičenih raztopin z UV-VIS spektroskopijo in lasersko difrakcijo

Pečovnik, Maruša (avtor), Bogataj, Marija (mentor)

Namen raziskovalnega dela v tej magistrski nalogi je spremljanje obarjanja natrijevega diklofenakata in dipiridamola iz prenasičenih raztopin. Njuna topnost je odvisna od pH, zato smo s spremembo pH sprožili proces obarjanja. V disperzni enoti analizatorja velikosti delcev smo istočasno vsako minuto od pričetka obarjanja delcev merili absorpcijske spektre s potopno sondo z optičnimi vlakni ter porazdelitev velikosti delcev. Zaradi sočasnih meritev smo naprej določili pogoje za ustrezno spremljanje obeh parametrov - korak merjenja, čas merjenja pri posamezni valovni dolžini in najkrajši čas med posameznimi meritvami za omogočeno vmesno čiščenje sonde, saj bi morebitni oborjeni delci na sondi lahko motili meritve. Preverili smo vpliv NaCl, HCl, Na3PO4 in polivinilpirolidona (PVP) na absorpcijske spektre in ugotovili, da ne motijo meritev. Ocenili smo vpliv možnega zaostanka medija v celici in cevkah analizatorja velikosti delcev na pH ter v skladu s tem izbrali primeren način priprave disperzne celice pred poskusi. Naši rezultati obarjanja iz prenasičenih raztopin kažejo, da se natrijev diklofenakat brez PVP obori hitro, večji delež delcev je mikrometrskih velikosti. Nasprotno pa dodatek polimera PVP upočasni potek obarjanja in rezultira v večinskem deležu delcev nanometrskih velikosti. Ponovljivost meritev pri poskusih obarjanja natrijevega diklofenakata z dodanim PVP je bila slaba. Raztopinam natrijevega diklofenakata z dodatkom PVP s koncentracijo 100 mg/L smo sprožili obarjanje pri različnih temperaturah in iz meritev razbrali, da procesi pri nižji temperaturi potekajo počasneje. Sami vodni raztopini natrijevega diklofenakata smo dodali različni koncentraciji NaCl ter s spremljanjem obarjanja spoznali, da je najvišja dodana koncentracija NaCl nekoliko pospešila obarjanje iz prenasičenih raztopin. Podobne poskuse smo izvedli tudi z dipiridamolom. Pripravili smo kisle vodne raztopine dipiridamola v 0,01 M HCl ter enake raztopine z dodatkom polimera PVP in tako preverili njegov vpliv na obarjanje. Rezultati izkazujejo vpliv polimera na obarjanje dipiridamola, vendar je ta manjši kot pri natrijevem diklofenakatu, saj se obarjanje pri dipiridamolu prične prej v primerjavi z obarjanjem natrijevega diklofenakata, večji delež delcev pa zavzema mikrometrske velikosti. Ugotovili smo tudi, da njegov vpliv na delež raztopljene učinkovine in porazdelitev velikosti delcev ni odvisen od preizkušenih koncentracij polimera.

• Jezik: Slovenski jezik
• Ključne besede: prenasičeno stanje, obarjanje, sočasno merjenje, porazdelitev velikosti delcev, UV-VIS spektroskopija
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2019
• PID: 20.500.12556/RUL-108554
• Datum objave v RUL: 06.07.2019

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Simultaneous monitoring of drug precipitation processes from supersaturated solutions by UV-VIS spectroscopy and laser diffraction

Izvleček

Aim of this master thesis was monitoring precipitation of diclofenac sodium and dipyridamole from their supersaturated solutions. Their solubility is pH-dependent, therefore the precipitation process was initiated by pH-change. Measurements of absorption spectra with a fiber optic dip probe and particle size distribution were performed simultaneously every minute after the beginning of precipitation in the dispersion cell of the particle size analyser. Since measurements were taken simultaneously, conditions had to be defined first in order to enable appropriate monitoring of both parameters - measurement step, measuring time at individual wavelength and the shortest time interval between two measurements due to cleaning of the dip probe (because of possibility of precipitated particles) were determined. The impact of NaCl, HCl, Na3PO4 and polyvinylpyrrolidone (PVP) on the absorption spectra was examined and found out not to influence the results of analyses. The impact of possible medium residue in the dispersion cell and corresponding tubes on pH values in the dispersion cell was evaluated and the most suitable process of preparation of dispersion cell before experiments was chosen. Results of precipitation from supersaturated solutions indicate that precipitation of diclofenac sodium without addition of PVP occurs fast and most particles are in micrometric size range. On the contrary, addition of polymer PVP decelerates the course of precipitation of diclofenac sodium and particle size results mainly in the nanoparticle range. Repeatability of measurements of precipitation of diclofenac sodium with addition of PVP was poor. In experiments with drug solutions, containing PVP concentration of 100 mg/L, precipitation at different temperatures was initiated. The results indicate that the lower the temperature is, the slower the processes are. Furthermore, different concentrations of sodium chloride were added to aqueous solutions of diclofenac sodium in order to monitor its effect on precipitation. Based on gathered information the highest added concentration of sodium chloride somewhat accelerated precipitation of diclofenac sodium from its supersaturated solutions. Similar experiments were made with dipyridamole. Acidic aqueous solutions of dipyridamole in 0,01 M HCl and same solutions with addition of two different concentrations of PVP were prepared and thus impact of polymer on drug precipitation was investigated. Based on the results, the polymer impacts precipitation of dipyridamole but its effect was minor compared to diclofenac sodium, since precipitation process is initiated earlier than precipitation of diclofenac sodium and most of particle size is in micrometric range. The tested concentration of the added polymer did not affect the percentage of the dissolved drug and particle size distribution.

• Ključne besede: supersaturation, precipitation, simultaneous measurements, particle size distribution, UV-VIS spectroscopy