Določanje hitrosti prepuščanja vlage skozi primarno ovojnino z uporabo radiofrekvenčnih transponderjev

Buzeti, Uroš (author), Srčič, Stanko (mentor), Markoja, Uroš (comentor)

Izbira prave primarne ovojnine je eden izmed ključnih korakov v razvoju zdravila. Njena naloga je zagotoviti učinkovitost zdravila skozi celoten predviden rok uporabnosti, s tem da ščiti zdravilo pred škodljivimi zunanjimi vplivi, ki lahko spremenijo njene lastnosti. Pri tem ima pomemben vpliv vlaga. Metoda radiofrekvenčnega prepoznavanja (RFID) ponuja nedestruktivni način merjenja sprememb notranje relativne vlage direktno v primarni ovojnini, v našem primeru v pretisnem omotu. V tej nalogi smo raziskovali zmožnosti metode radiofrekvenčnega prepoznavanja za kvantificiranje hitrosti prepuščanja vodne pare in primerjali njene rezultate z USP <671> metodo. Testirali smo PVC 250, PVC/PVDC 200/60, PVC/PVDC 250/120, PVC/PE/PVDC 250/25/180 in PVC/Aclar® 254/76 oblikovane v mehurčke z okroglim dnom velikosti 9x5 mm, 10x5 mm, 11x6 mm, 13x5 mm in 15x6 mm. Te konfiguracije so bile izpostavljene klimatskim pogojem 30°C/75% RH, 40°C/75% RH in 50°C/75% RH. Vsaka konfiguracija je bila zastopana s štirimi RFID transponderji, od katerih je bila ena tretjina kalibriranih s certifikatom s strani Microsensys. S to metodo smo opazili statistično signifikantne razlike notranje relativne vlažnosti po blistiranju med različnimi polimernimi filmi. Eksperimentalne meritve relativne vlage smo prilegali krivulji iz katere smo izpostavili časovne konstante konfiguracij. Rezultate med uporabljenimi polimernimi filmi smo primerjali in določili, da ima PVC 250 najslabšo zaščito proti vodni pari, medtem ko imata PVC/PE/PVDC 250/25/180 in PVC/Aclar® 254/76 najboljšo. Velikost 9x5 mm je pričakovano imela najvišjo časovno konstanto, 15x6 mm pa najnižjo. Časovna konstanta je zanimivo druga najvišja pri velikosti 13x5 mm, sledi ji 10x5 mm, medtem ko je pri 11x6 mm druga najnižja. Časovne konstante se nižajo z višanjem temperature. Vse rezultate radiofrekvenčne metode smo primerjali z rezultati USP <671> metode, ki so pokazali podobne razlike razmerij med posameznimi primerjavami. Zatem smo poskušali izračunati hitrost prepuščanja vodne pare s pomočjo časovne konstante. To nam ni uspelo zaradi nepoznavanja debeline stene mehurčka pretisnega omota in ker model ni upošteval njenega postopnega zmanjševanja. Rezultati kažejo potencial, da se metodo radiofrekvenčnega prepoznavanja uporabi kot dodatek stabilnostnim študijam. Z dodatnimi eksperimentalnimi poskusi in z izboljšanim modelom lahko postane primarna metoda pri izbiranju primarne ovojnine.

• Language: Slovenian
• Keywords: radiofrekvenčno prepoznavanje, hitrost prepuščanja vodne pare, primarna ovojnina, permeabilnost, časovna konstanta
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2019
• PID: 20.500.12556/RUL-113348
• Publication date in RUL: 21.12.2019

Secondary language

• Language: English
• Title: Determination of water vapour transmission rate through primary packaging using radio-frequency transponders

Abstract

Choosing the right primary packaging is one of the most important steps in drug development. Its role is to assure drug efficacy through the intended shelf life while protecting it from all adverse external influences that can change its properties, an important one being moisture. Radio-frequency identification (RFID) method offers a nondestructive way of measuring internal changes of relative humidity directly in the primary packaging - in our case inside a blister cavity. In this thesis, we explore the capabilities of the RFID method to quantify the water vapor transmission rate and compare the results with the USP <671> method. We tested PVC 250, PVC/PVDC 200/60, PVC/PVDC 250/120, PVC/PE/PVDC 250/25/180 and PVC/Aclar® 254/76 formed in round blister cavity sizes of 9x5 mm, 10x5 mm, 11x6 mm, 13x5 mm and 15x6 mm. These configurations were exposed to climate conditions of 30°C/75% RH, 40°C/75% RH and 50°C/75% RH. Each configuration was represented with 4 RFID transponders, out of which a third was calibrated by the Microsensys company. With this method we noticed statistically significant changes of RH after the blistering procedure. Through a fit of experimental relative humidity measurements, we extracted the time constant. We compared the results between polymer films used and determined that PVC 250 has the worst water vapor barrier, whereas PVC/PE/PVDC 250/25/180 and PVC/Aclar® 254/76 the best. Size 9x5 mm expectedly had the highest time constant and size 15x6 mm the lowest. Interestingly, the time constant was second highest with 13x5 mm followed by 10x5 mm, whereas 11x6 mm had the second lowest. The time constants decreased with increasing temperature, as expected. All RFID results were compared to the results of the USP <671> method and showed similar difference ratios in these comparisons. Subsequently we tried to calculate the water vapor transmission rate through the extracted time constant. This was not achieved, due to the unknowing wall thicknesses of the blister cavities and the model not being complex enough to take this into account. In summary, our results show that RFID method can be used as a supplement to the stability studies. With additional experimentation and improvements to the model it has the potential to become the method of choice for selection of primary packaging.

• Keywords: radio-frequency identification, water vapor transmission rate, primary packaging, permeability, time constant