Termodinamske lastnosti dvofaznega sistema polimer trilaurin/superkritični CO2 in formulacija zdravilnih učinkovin

diplomsko delo univerzitetnega študijskega programa I. stopnje

Kaja Zadravec (Author), Maša Knez Hrnčič (Mentor), Gregor Kravanja (Mentor)

Abstract

Diplomsko delo zajema študijo fizikalno-kemijskih in transportnih lastnosti dvofaznega sistema trilaurin/superkritični CO2 ter formulacijo aktivne učinkovine nimodipina v trilaurinsko matrico z uporabo superkritičnih fluidov. Visokotlačni procesi z uporabo superkritičnih fluidov so trajnostni, okolju prijazni in ekonomsko ugodni ter imajo široko paleto uporabe. Uporabljajo se v vedno večjem obsegu v farmacevtski, živilski, tekstilni in kemični industriji. Kot supekritični fluid smo uporabili okolju prijazen in termodinamsko stabilen supekritični CO2. Določili smo gostoto za binarni sistem (trilaurin/superkritični CO2) v območju tlakov med 0,1 MPa in 35 MPa pri dveh izotermah (60 °C in 80 °C) z uporabo visokotlačne metode z nihajočo U-cevko. Pri istih pogojih smo določili površinsko napetost binarnega sistema s kapilarnim dvigom in kapljično metodo, kjer smo ugotovili, da sta metodi med sabo dokaj primerljivi. Z magnetno suspenzijsko tehtnico smo za binarni sistem določili topnosti in difuzijske koeficiente. Tališče smo določili z visokotlačno kapilarno metodo in s pomočjo TGA/DSC analize. Pri atmosferskem tlaku znaša tališče polimera trilaurin 44,7 °C in ima talilno krivuljo dP/dT z negativnim naklonom. Podatke termodinamičnih lastnosti preučevanega dvofaznega sistema smo uporabili za določitev optimalnih parametrov za izvedbo visokotlačne mikronizacije. Kot nosilno matriko smo uporabili polimer trilaurin in nanj vezali v vodi slabo topno učinkovino nimodipin. Dobljeni praškasti produkt smo analizirali z LC-MS/MS metodo in ugotovili, da se je po pršenju vsebnost nimodipina v trilaurnski matrici ohranila in znašala 94,97 %. Izvedli smo test sproščanja zdravilne učinkovine, kjer smo simulirali pogoje v želodcu pri 0,1 M vodni raztopini HCl ter tako dobili hitrostne profile raztapljanja zmesi nimodipina trilaurin/nimodipin. Potrdili smo, da je bil profil raztapljanja nimodipina, obdelanega s mikronizacijskim postopkom PGSS, 2‒3-krat višji napram neprocesiranemu nimodipinu.

Keywords

superkritični CO2;trilaurin;površinske napetosti;topnosti;mikronizacija;nimodipin;LC-MS/MS analiza;diplomske naloge;

Data

Language:	Slovenian
Year of publishing:	2019
Typology:	2.11 - Undergraduate Thesis
Organization:	UM FKKT - Faculty of Chemistry and Chemical Engineering
Publisher:	[K. Zadravec]
UDC:	66.083:54-139(043.2)
COBISS:	22624790
Views:	784
Downloads:	130
Average score:	0 (0 votes)
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Other data

Secondary language:	English
Secondary title:	Thermodynamic properties of the trilaurin polymer/supercritical CO2 and the formulation of the active substance
Secondary abstract:	The thesis work includes a study of the physico-chemical and transport properties of the two-phase system trilaurin/supercritical CO2 and the formulation of the active medicinal properties of nimodipine into the trilaurin matrix. High pressure processes using supercritical fluids are sustainable, environmentally friendly and economically advantageous and have a wide range of applications. They are increasingly used in the pharmaceutical, food, textile and chemical industries. As a supercritical fluid we have used an environmentally friendly and thermodynamically stable supercritical CO2. The density for the binary system (trilaurin/supercritical CO2) was determined in the pressure range between 0,1 MPa and 35 MPa at two isotherms (60 °C and 80 °C) using a high pressure method with a swinging U-tube. Under the same conditions the surface tension of the binary system by capillary rise method and the drop method has been determined; by doing that we have learned that the methods are relatively comparable to each other. With the magnetic suspension balance we have determined solubility and diffusion coefficients for the binary system. The melting point has been determined by high-pressure capillary method and by TGA/DSC analysis. At atmospheric pressure, the melting point of the polymer trilaurin is 44.7 °C and melting curve has a negative dp/dT slope. Data of the thermodynamic properties of the studied two-phase system have been used to determine the optimal parameters for the implementation of high-pressure micronisation. Polymer trilaurin has been used as a carrier matrix and it was tied to the low-soluble (in water) active medicinical properties of nimodipine. The resulting powder product has been analysed using the LC-MS/MS method and the results show that after spraying, the content of nimodipine in the trilaurin matrix is maintained at 94,97%. We have implemented the dissolution test of medicinal properties, where we have simulated stomach conditions in a 0,1 M aqueous HCl solution to obtain the dissolution profiles of the nimodipine triilaurin / nimodipine mixture. We have confirmed that the dissolution profile of nimodipine treated with the micronization process PGSS has been 2-3 times higher than the untreated nimodipine.
Secondary keywords:	supercritical CO2;trilaurine;surface tension;solubility;micronization;nimodipine;LC-MS/MS analysis;
Type (COBISS):	Bachelor thesis/paper
Thesis comment:	Univ. v Mariboru, Fak. za kemijo in kemijsko tehnologijo
Pages:	XIII, 73 str.
ID:	11205445