Vrednotenje vpliva interakcij med natrijevim lavrilsulfatom in hidroksipropilmetilcelulozo na nabrekanje in sproščanje iz tablet

Perko, Anja (author), Bogataj, Marija (mentor)

V magistrski nalogi smo raziskovali vpliv interakcij med natrijevim lavrilsulfatom (SDS) in hidroksipropilmetilcelulozo (HPMC) na nabrekanje ogrodnih tablet s HPMC-jem in na sproščanje natrijevega diklofenakata (NaDF) iz tablet. Poskuse sproščanja in nabrekanja smo izvajali v koncentriranem (KMB) in 4-krat redčenem (DMB) McIlvaineovem pufru s pH 4 z dodanim SDS-om v koncentracijskem območju od 0 do 0,25 m/V %. Uporabili smo dve vrsti tablet s HPMC-jem – tablete z NaDF in tablete brez učinkovine (prazne tablete). Teste sproščanja in nabrekanja smo izvajali s farmakopejsko napravo z vesli (naprava II) s sistemom za video nadzor sproščanja DissoGUARD®, v 900 mL medija pri 37 ± 0,5 °C in pri 75 obratih na minuto. Nabrekanje tablet smo ovrednotili z dvema metodama – z merjenjem premera in debeline tablet na slikah, posnetih med poskusom sproščanja, ter s tehtanjem tablet. Pri spremljanju nabrekanja tablet z NaDF med testiranjem sproščanja v DMB-ju smo ugotovili, da tablete bolj nabrekajo pri koncentracijah SDS-a pod CMC (0,05–0,07 %), najbolj pa v DMB-ju z 0,05 % SDS-a. Največ NaDF se sprosti v DMB-ju z 0,25 % SDS-a, kjer tablete najmanj nabrekajo. Najmanj NaDF se sprosti v DMB-ju z 0,05 % SDS-a, kjer tablete najbolj nabrekajo. Tablete z NaDF so v KMB-ju z dodanim SDS-om razpadle, zato nabrekanja v tem primeru nismo mogli spremljati. Takoj po razpadu je bila verjetno topnost presežena, zato koncentracija s časom pada. Višja kot je bila koncentracija SDS-a v KMB-ju, večji je bil izmerjen delež sproščenega NaDF po 4-ih urah. Izjema je območje od 0,07 do 0,09 % SDS-a. V DMB-ju se po 4-ih urah delež sproščenega NaDF ni večal s koncentracijo SDS-a – delež sproščenega NaDF je narasel v DMB-ju z 0,01 % SDS-a, vendar je pri 0,05 % SDS-a padel in nato dalje naraščal s koncentracijo SDS-a. Opazili smo odstopanja pri naslednjih koncentracijah SDS-a: 0,05–0,06 % SDS-a v DMB-ju in 0,07–0,09 % SDS-a v KMB-ju. Ta odstopanja smo pripisali interakcijam med SDS-om in HPMC-jem. Nabrekanje praznih tablet smo spremljali pri enakih pogojih kot testiranje sproščanja, le da v tem primeru nismo vzorčili. Pri 4-urnem poskusu smo ugotovili, da z vmesnim tehtanjem, in s tem z jemanjem tablet iz posod za testiranje sproščanja, vplivamo na rezultate nabrekanja praznih tablet, saj so bile mase in dimenzije tablet v tem primeru večje kot pri tehtanju praznih tablet samo po koncu poskusa nabrekanja. Relativna sprememba debeline in mase praznih tablet po 4-ih in 24-ih urah nabrekanja je bila največja v KMB-ju z 0,05 % SDS-a. V DMB-ju je bilo povečanje debeline praznih tablet največje v mediju z 0,07 % SDS-a, povečanje mase praznih tablet pa v mediju z 0,05 % SDS-a. Podobni rezultati nabrekanja praznih tablet in tablet z NaDF v DMB-ju nakazujejo na to, da NaDF ne vpliva na proces nabrekanja v DMB-ju, in da so odstopanja v območju 0,05–0,07 % SDS-a lahko posledica interakcij med SDS-om in HPMC-jem.

• Language: Slovenian
• Keywords: sproščanje, nabrekanje tablet, interakcije med natrijevim lavrilsulfatom in hidroksipropilmetilcelulozo
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2019
• PID: 20.500.12556/RUL-108330
• Publication date in RUL: 28.06.2019

Secondary language

• Language: English
• Title: The evaluation of sodium lauryl sulphate and hydroxypropylmethylcellulose interactions effect on swelling and release from tablets

Abstract

The aim of this thesis was to evaluate effect of interactions between the sodium lauryl sulfate (SDS) and hydroxypropylmethylcellulose (HPMC) on swelling and release of diclofenac sodium (NaDF) from matrix tablets with HPMC. The media used in dissolution and swelling tests were concentrated (KMB) and four times diluted (DMB) McIlvaine buffer with pH 4 and addition of SDS in the concentration range of 0 to 0,25 w/V %. We used two types of tablets with HPMC – tablets with and without NaDF. The experiments were performed using paddle apparatus (Apparatus II) as described in Pharmacopoeia with video recording system DissoGUARD® placed underneath the dissolution bath and with 900 mL of medium at 37 ± 0,5 °C and 75 rpm. Tablet swelling was evaluated using two different methods – measuring the dimensions on photos taken between the dissolution testing and tablet weighing. In DMB tablets with NaDF swelled more at SDS concentrations bellow CMC value (0,05–0,07 % SDS) and the most in DMB with 0,05 % SDS. At this concentration the percentage of NaDF dissolved was the lowest. The highest amount of NaDF was released in DMB with 0,25 % SDS where tablets swelled the least. Tablets with NaDF disintegrated in KMB with added SDS, so swelling could not be measured. We assume that surplus solubility was achieved after tablets disintegrated, consequently concentration of NaDF decreased with time. Larger SDS concentrations in KMB released more NaDF after 4 hours in whole concentration range, except in concentration range from 0,07 % to 0,09 % SDS. In contrast, larger SDS concentrations in DMB released more NaDF after 4 hours only in concentration range from 0,05 % to 0,25 % SDS. The dissolution of NaDF in DMB with 0,01 % SDS was higher than in DMB with 0,05 % SDS. We noticed deviations at the following concentrations: 0,05–0,06 % SDS in DMB and 0,07–0,09 % SDS in KMB which we ascribed to SDS and HPMC interactions. Swelling of tablets without NaDF was examined under the same conditions as tablets with NaDF during dissolution testing only without sampling. The 4 hour swelling test showed that interim weighing of tablets during the dissolution testing resulted in larger tablets dimensions and masses than weighing tablets just after 4 hours. The 4 and 24 hour test in KMB showed tablets without NaDF swelled the most in media with 0,05 % SDS. In DMB the largest increase in thickness of tablets without NaDF was observed in media with 0,07 % SDS and the largest increase in mass was observed in 0,05 % SDS. Similar swelling results of tablets with and without NaDF show NaDF does not affect swelling process in DMB. Therefore deviations in concentration range from 0,05 % to 0,07 % SDS may be attributed to SDS and HPMC interactions.

• Keywords: Dissolution, tablet swelling, SDS and HPMC interactions