Vpliv biorelevantnih parametrov na raztapljanje in sproščanje cinarizina v simuliranih pogojih s hrano

Dular, Jože (author), Bogataj, Marija (mentor)

V magistrski nalogi smo analizirali sproščanje in raztapljanje cinarizina v vodni fazi in na ta način spremljali tudi porazdeljevanje v oljno fazo. Uporabili smo več različnih vodnih medijev in sicer 4x redčen Mcllvainov pufer (DMB) z različnimi pH vrednostmi, DMB pH 3, DMB pH 4 in DMB pH 5 ter 0,001 M HCl. K njim smo kot ponazoritev vpliva hrane dodajali olivno ali ribje olje. Preverili smo različne vplive kot so vpliv količine natehtane zdravilne učinkovine, pH medija, dodanega NaCl in volumna dodanega olja na raztapljanje zdravilne učinkovine. Preverili smo vpliv različnih koncentracij vnaprej raztopljene zdravilne učinkovine v vodnem mediju na porazdeljevanje v olje. Poleg tega smo naredili tudi primerjavo med sproščanjem iz tablet in raztapljanjem enake količine natehtane zdravilne učinkovine. Koncentracijo raztopljenega cinarizina smo izračunali s pomočjo umeritvenih premic iz absorbanc UV spektra in površin pod vrhovi na kromatogramih. Te smo izmerili z UV-VIS spektrofotometrom ter z HPLC. V vsakem mediju smo preverili tudi topnost cinarizina. Iz dobljenih rezultatov lahko sklenemo, da je učinkovina veliko bolje topna pri nizkih pH vrednostih, kar je v skladu z dejstvom, da je šibka baza. Dodatek olja na začetku pospeši raztapljanje zdravilne učinkovine v vodni fazi, nato pa po določenem času zmanjševati odstotek raztopljene zdravilne učinkovine v vodni fazi, saj se začne učinkovina porazdeljevati v olje. Iz preveritve vpliva volumna dodanega olja na raztapljanje učinkovine ne moremo prikazati vpliva, saj rezultati ne sledijo nobenemu vzorcu. Iz analiz smo ugotovili tudi, da dodajanje NaCl v medij DMB pH 3 zvišuje odstotek raztopljene učinkovine v vodni fazi. Pri porazdeljevanju predhodno raztopljene učinkovine v olje, koncentracija učinkovine nima vpliva. Med rezultati sproščanja iz tablet in raztapljanja enake količine natehtane učinkovine brez dodanega olja vidimo, da je v prvih treh urah sproščanje iz tablet hitrejše, a pri končnem času razlik praktično ni. Pri primerjavi raztapljanja v prisotnosti olja se pri tableti sprosti okoli 10 % več učinkovine.

• Language: Slovenian
• Keywords: sproščanje, raztapljanje, porazdeljevanje, zdravilna učinkovina, olje, cinarizin, spektrofotometrična določitev
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2025
• PID: 20.500.12556/RUL-167961
• Publication date in RUL: 21.03.2025

Secondary language

• Language: English
• Title: Influence of biorelevant parameters on dissolution and release of cinnarizine under simulated fed state conditions

Abstract

In this thesis we analyzed the release and dissolution of cinnarizine in water phase and thus followed also the distribution in oil phase. As aqueous media we used 4x diluted Mcllvain's buffer (DMB) with pH 3, pH 4 , pH 5 and 0.001 M HCl. Olive or fish oil was then added as an illustration of food influence. We checked various influences on the dissolution of active ingredient such as amount of weighed active ingredient, pH of the medium, addition of NaCl and volume of added oil. We also checked the influence of different concentrations of pre-dissolved active ingredient in the water phase on the distribution in oil. Comparison between the release from the tablets and dissolution of the same amount of the weighed active ingredient was also made. The concentration of released cinnarizine was calculated with absorbances and areas measured with a UV-VIS spectrophotometer and HPLC. We also checked the solubility of cinnarizine in each medium. The results show that cinnarizine is much more soluble at low pH values, which is in line with the fact that our active ingredient is weak base. The addition of oil initially accelerates the dissolution of the active ingredient in the water phase. Then after a certain time the addition of oil begins to reduce the percentage of dissolved active ingredient in water phase as the active ingredient begins to distribute into oil. We cannot show any effect of addition of different volumes of oil because results do not follow any pattern. Addition of NaCl to the DMB pH 3 medium increases the dissolution of cinnarizine. The concentration of previously dissolved active ingredient in the water media has no effect on distribution in oil. When we compare the release of active ingredient from the tablets and the dissolution of the same amount of weighted active ingredient, we can see that the release from the tablets is faster in the first three hours but at the end there are no differences. In the presence of oil about 10 % more of the active ingredient is released from the tablet compared to the dissolution of the same amount of weighed active ingredient.

• Keywords: release, dissolution, distribution, active ingredient, oil, cinnarizin, spectrophotometric determination.