Vpliv nabrekanja tablet, topnosti učinkovine in prevodnosti medija z natrijevim lavrilsulfatom na sproščanje iz ogrodnih tablet s hidroksipropilmetilcelulozo

Štrancar, Tjaša (author), Bogataj, Marija (mentor)

V magistrski nalogi smo preučevali interakcijo med natrijevim lavrilsulfatom (SDS) v mediju za sproščanje in hidroksipropilmetilcelulozo (HPMC) v ogrodni tableti. Zanimalo nas je, kako ta interakcija vpliva na sproščanje težko topne zdravilne učinkovine natrijevega diklofenakata (Na-DF). V ta namen smo testirali sproščanje Na-DF iz ogrodnih tablet s HPMC. Sproščanje smo izvajali v Napravi II po USP v 4-krat redčenih Mcllvainovih pufrih (DMB) različnih pH vrednostih in s koncentracijami SDS-a od 0,05 − 1 %. Ugotovili smo, da se je v DMB pH 4 z 0,05 % SDS-a in DMB pH 7 z 0,05 % SDS-a po 4 urah sproščanja sprostilo manj učinkovine kot v samem DMB. Med testiranjem sproščanja smo spremljali nabrekanje tablet z merjenjem višine in premera le-teh. Nato smo izračunali volumne tablet. Pri DMB pH 3 in pH 4 smo po 4 urah sproščanja opazili, da volumen tablet narašča v medijih brez SDS-a in z 0,05 % SDS-a, pri višjih koncentracijah SDS-a pa pada. Pri DMB pH 7 je volumen tablet najnižji pri 0,05 % SDS-a, nato malo naraste in pri koncentraciji 0,1 % SDS-a ponovno začne padati. Pri opazovanju nabrekanja tablet brez Na-DF v DMB pH 3 volumen tablet narašča vse do 0,06 % SDS-a in pada pri večjih koncentracijah SDS-a. Z metodo merjenja prevodnosti raztopin SDS-a v vodi in v DMB pH 4, smo SDS-u določili vrednosti kritične micelske koncentracije (CMC). V medijih, kjer je bila prisotna tudi HPMC, pa smo določili vrednosti kritične agregacijske koncentracije (CAC) in točko nasičenosti polimera (PSP). Vrednost CMC v vodi je bila višja kot v DMB pH 4. Vrednost CAC se je v vodi nekoliko spreminjala s koncentracijo HPMC, PSP pa naraščala. Pri DMB pH 4 pa so vrednosti CAC naraščale z naraščajočo koncentracijo HPMC, vrednosti PSP pa so se neenakomerno spreminjale. V DMB različnih pH vrednosti z in brez HPMC in z različno koncentracijo SDS-a smo določili topnost Na-DF. Le-ta je v DMB pH 3 in pH 4 naraščala z naraščajočo koncentracijo SDS-a, tako v medijih brez, kot z dodano HPMC. Dodatek HPMC v medij, je nekoliko povečal topnost Na-DF, napram medijem brez dodane HPMC. Pri merjenju transmitance v DMB pH 3 z različnimi koncentracijami SDS-a in HPMC smo ugotovili, da transmitanca vzorcev pada z naraščajočo koncentracijo HPMC in SDS-a, vse do koncentracije SDS-a 0,1 %, nato pa ponovno narašča. Pri vseh uporabljenih metodah smo opazili nepričakovane rezultate pri podobnih koncentracijah SDS-a (0,05-1 %) , kar bi lahko nakazovalo na interakcije med SDS in HPMC pri teh koncentracijah.

• Language: Slovenian
• Keywords: sproščanje Na-DF, nabrekanje tablet, električna prevodnost, topnost, transmitanca, interakcija med SDS-om in HPMC
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2019
• PID: 20.500.12556/RUL-107427
• Publication date in RUL: 12.04.2019

Secondary language

• Language: English
• Title: The influence of tablet swelling, drug solubility and conductivity of mediacontaining sodium lauryl sulfate on dissolution from the hydroxypropyl methylcellulose tablets

Abstract

The aim of this thesis was to study the interaction between sodium lauryl sulfate (SDS) and hydroxypropyl methylcellulose (HPMC). Specifically how this interaction influences the release of diclofenac sodium (Na-DF) from matrix tablets with HPMC. The release of Na-DF from matrix tablets was tested in apparatus 2 (USP) in diluted Mcllvain buffers (DMB) with different pH and SDS concentrations from 0,05-1 %. The percentage of Na-DF released in DMB pH 4 with 0,05 % SDS and DMB pH 7 with 0,05 % SDS was smaller than in DMB media without SDS. During the dissolution testing, the swelling of tablets was examined by measuring their height and diameter. The 4 hour test in DMB pH 3 and pH 4 showed the volume of tablets increased until the concentration of SDS reached 0,05 %, afterward the volume started to decrease. In DMB pH 7 the volume decreased until 0,05 % of SDS, then started increasing reaching the peak at 0,1 % and then decreased again. When examining the swelling of tablets without Na-DF in DMB pH 3 the volume increased until 0,06 % of SDS and decreased with higher SDS concentrations. Using the conductometric method the critical micelle concentrations (CMC) of SDS in water and DMB pH 4 was determined. The same media with added HPMC were used to determine the critical aggregation concentration (CAC) and polymer saturation point (PSP). CMC values in water were higher than in DMB pH 4. With higher HPMC concentrations CAC values in water changed nonlinearly while PSP values increased. In DMB pH 4, CAC values increased with higher HPMC concentrations and PSP values changed nonlinearly. Solubility of Na-DF was determined in DMB media with different pH, with and without HPMC and with different SDS concentrations. In DMB pH 3 and pH 4 media with and without HPMC, the solubility increased with higher SDS concentrations. The addition of HPMC in media increased the solubility of Na-DF in comparison with media without HPMC. By measuring the transmittance of samples in DMB pH 3 with different SDS and HPMC concentrations, the transmitance was found to decrease with higher SDS and HPMC concentrations until 0,1 % of SDS. When concentrations of SDS increased above 0,1 % the transmittance increased. We noticed unexpected results at similar SDS concentrations (0,05-0,1 %) at all experimental methods we used, which can indicate possible interactions between SDS and HPMC at these concentrations.

• Keywords: release of Na-DF, swelling of tablets, electrical conductivity, solubility, transmittance, SDS-HPMC interaction