Ponazarjanje vpliva zaužite vode na sproščanje paracetamola iz ogrodnih tablet z različnimi kinetikami sproščanja

Jus, Amadeja (author), Bogataj, Marija (mentor), German Ilić, Ilija (co-mentor)

Na sproščanje učinkovine po peroralni aplikaciji vpliva veliko fizioloških parametrov, en izmed zelo pomembnih je volumen, ki je na voljo za raztapljanje farmacevtske oblike. Da bi ugotovili, ali na sproščanje učinkovine vpliva 240 mL zaužite vode, s katero se po smernicah FDA aplicira zdravilo, hkrati pa ta volumen zadošča tudi predpisu EMA, smo preskušali sproščanje paracetamola iz ogrodnih tablet pod vplivom različnih ponazorjenih profilov praznjenja želodčne tekočine v pretočnem sistemu. Pretočni sistem s kroglicami smo postavili tako, da smo v delovno čašo z eno peristaltično črpalko konstantno dovajali 0,01 M HCl, s čimer smo ponazarjali izločanje želodčne kisline, z drugo črpalko pa smo črpali vsebino iz čaše. Profile praznjenja, po katerih smo vsebino črpali iz čaše, smo povzeli iz literature in jih prilagodili zgolj toliko, da smo lahko izvedli poskuse z opremo, ki nam je bila na voljo. Primerjali smo sproščanje paracetamola pod vplivom treh ponazorjenih profilov praznjenja 240 mL vode – po hitrem, počasnem in povprečnem. Rezultate smo primerjali s sproščanjem paracetamola zgolj v 40 mL 0,01 M HCl in s konstantnim pretokom 2 mL/min na obeh črpalkah, kar je ponazarjalo stanje v želodcu na tešče. Testirali smo 12 različnih tablet z različnimi kinetikami sproščanja, ki so se večinoma razlikovale le po vrsti in deležu polimera. Ugotovili smo, da na obseg in hitrost sproščanja učinkovine vpliva profil praznjenja tekočine iz želodca. Večjo razliko med profilom sproščanja s konstantnim pretokom in ob ponazarjanju profila praznjenja smo opazili pri tabletah iz katerih se je učinkovina sprostila zelo hitro, najmanjšo pa pri tistih, katerih sproščanje učinkovine je bilo zelo počasno. Hkrati smo pri vseh testiranih tabletah opazili največje razlike v sproščanju, ko smo sproščanje s konstantnim pretokom primerjali s sproščanjem ob ponazarjanju hitrega profila praznjenja, najmanjše pa ob primerjavi s sproščanjem ob ponazorjenem počasnem profilu praznjenja. Glede na rezultate lahko torej predvidevamo, da zaužita voda do neke mere vpliva na obseg in hitrost sproščanja paracetamola iz farmacevtske oblike, vendar bi bilo za bolj točne informacije treba izvesti še nadaljnje raziskave in preskusiti sproščanje tudi drugih, slabše topnih učinkovin, na katerih sproščanje ima volumen lahko večji vpliv.

• Language: Slovenian
• Keywords: paracetamol, pretočni sistem, voda, testi sproščanja, profili praznjenja
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2020
• PID: 20.500.12556/RUL-119875
• Publication date in RUL: 12.09.2020

Secondary language

• Language: English
• Title: Simulation of ingested water influence on paracetamol release from matrix tablets with different drug release kinetics

Abstract

After oral administration many physiological parameters play an important role in drug dissolution. And one of them is definitely volume of the media in the gastrointestinal tract, because it defines the amount of liquid available for drug dissolution. According to FDA and EMA a medication administered under fasted conditions should be taken with 240 mL or at least 150 mL of water. To establish whether this amount of water influences drug dissolution, we have simulated paracetamol release under simulation of different gastric emptying profiles in a flow-through system. The flow-through system with glass beads consisted of a working beaker and two peristaltic pumps. One was used to pump 0,01 M HCl with a constant rate of 2 mL/min into the beaker, which simulated excretion of gastric acid, and the other one was used to pump the contents out of the beaker. Gastric emptying profiles after intake of 240 mL of water that were used as a basis for simulating gastric empyting in the flow-through system were obtained from a scientific article, and were modified just slightly to perform the experiments with the use of available equipment. We compared paracetamol release following 3 different gastric emptying profiles – fast, slow and average. Results obtained with these 3 emptying profiles were compared to dissolution of paracetamol in 40 mL of 0,01 M HCl, when both peristaltic pumps were working at the rate 2 mL/min, which simulated gastric conditions in the fasted state. We tested 12 formulations with different drug release kinetics. Most of them only differentiated in amount and/or type of polymer used. We have noticed the amount and rate of drug release were influenced by simulated gastric emptying. The biggest difference between drug dissolutions profiles were noticed when testing paracetamol release with constant flow rate of 2 mL/min and under different emptying profiles in formulations with the fastest drug release kinetics. We have also found the biggest differences when comparing paracetamol dissolution under constant flow rate of 2 mL/min and simulated fast emptying profiles, and in contrast, the smallest differences in dissolution profiles when comparing with simulated slow emptying profiles. The results therefore hint the water ingested with medication could impact paracetamol dissolution, but further investigation, especially with other, less-soluble active pharmaceutical ingredients, should be conducted before coming to any conclusions.

• Keywords: paracetamol, flow-through system, water, dissolution tests, gastric emptying profiles