Vrednotenje interakcij med natrijevim lavrilsulfatom in hidroksipropilmetilcelulozo z določanjem motnosti ter njihov vpliv na sproščanje izbrane zdravilne učinkovine iz tablet

Lozar, Janja (author), Bogataj, Marija (mentor)

V magistrski nalogi smo proučevali vpliv interakcij med natrijevim lavrilsulfatom (SDS) in hidroksipropilmetilcelulozo (HPMC) na motnost disperzij z merjenjem transmitance. Zanimal nas je tudi vpliv omenjenih interakcij na nabrekanje ogrodnih tablet s HPMC in sproščanje natrijevega diklofenakata (Na-DF) iz le-teh. Medij, ki smo ga uporabljali pri poskusih, je bil 4-krat redčen McIlvainov pufer (DMB) s pH 4. Pri spremljanju transmitance smo raztopino SDS (1 %, 5 % oz. 10 % (m/V)) v zaporednih dodatkih po 0,5 mL dodajali v disperzijo HPMC (0,3 g/L – 10,0 g/L) in po vsakem dodatku pomerili transmitanco disperzije z UV-VIS spektrofotometrom s potopno sondo z optičnimi vlakni (sonda). Nato smo pripravili disperzije s konstantnimi koncentracijami HPMC in SDS in izmerili njihovo transmitanco s sondo in v kiveti. Meritve na obeh spektrofotometrih smo primerjali med seboj. Primerjali smo tudi transmitance disperzij z različnimi koncentracijami SDS in HPMC. Transmitanca disperzij HPMC in SDS se je začela zniževati pri 0,05 % SDS v disperziji, ne glede na koncentracijo polimera. Z višanjem koncentracije SDS se je transmitanca zmanjševala, nato pa v določeni točki dosegla minimum. Pri še višjih koncentracijah SDS je transmitanca spet začela naraščati. Pri nižjih koncentracijah HPMC (0,3 – 2,0 g/L) smo okoli 0,10 % SDS v disperziji opazili nastanek skupka, pri višjih (5,0 – 10,0 g/L)pa do tega ni prišlo, ampak je po celotnem volumnu disperzije pri koncentraciji SDS okoli 0,40 % nastala na videz zelo viskozna zmes.Na-DF na transmitanco disperzij ni vplival. Sproščanje Na-DF iz ogrodnih tablet s HPMC smo izvajali na napravi z vesli po USP (Naprava II) v DMB s pH 4 z dodanim SDS v koncentracijskem območju od 0,0 do 0,20 m/V %. SDS, dodan v medij za sproščanje, je v večini primerov pospešil sproščanje Na-DF iz tablet, le pri 0,05 % in 0,07 % SDS, dodanega v DMB, smo opazili nižji % sproščene učinkovine kot v samem DMB. Nabrekanje tablet smo spremljali med poskusom sproščanja, in sicer smo s sistemom za video nadzor sproščanja DissoGUARD® pred začetkom poskusa in v osmih časovnih točkah vzorčenja posneli slike, na slednjih pa nato določili premer in debelino tablet in izračunali relativne indekse premera in debeline. Nabrekanje je bilo pri 0,05 % SDS v smeri obeh dimenzij tablet večje kot pri nižjih in višjih koncentracijah SDS v mediju.Tablete smo tudi tehtali, in sicer pred začetkom poskusa sproščanja in po končanem 4-urnem sproščanju. Največji prirast mase je bil prav tako v DMB z 0,05 % SDS. Pri spremljanju motnosti smo znižanje % transmitance najprej zaznali pri 0,05 % SDS v disperziji, ne glede na koncentracijo HPMC. Pri koncentracijah 0,05 % in 0,07 % SDS, dodanega v DMB je bilo sproščanje Na-DF zmanjšano in nabrekanje tablet povečano v primerjavi s samim DMB. Lahko, da gre za odraz interakcij med HPMC in SDS.

• Language: Slovenian
• Keywords: Interakcije med SDS in HPMC, motnost, transmitanca, UV-VIS spektrofotometer, potopna sonda z optičnimi vlakni, sproščanje, nabrekanje tablet
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2019
• PID: 20.500.12556/RUL-111442
• Publication date in RUL: 01.10.2019

Secondary language

• Language: English
• Title: Evaluation of sodium lauryl sulphate and hydroxypropyl methylcellulose interactions with turbidity determination and their effect on selected drug release from tablets

Abstract

In this master's thesis, we studied the impact of interactions between sodium lauryl sulphate (SDS) and hydroxypropyl methylcellulose (HPMC) on turbidity of dispersions with transmittance measurements. We were also interested in the influence of these interactions on swelling of the matrix tablets with HPMC and release of diclofenac sodium (Na-DF) from these tablets. The medium used in experiments was 4-times diluted McIlvain buffer (DMB) with pH 4. Firstly, the solution of SDS (1 %, 5 % or 10 % (w/V)) was added into the dispersion of HPMC (0.3 g/L – 10.0 g/L) in sequential 0,5 mLadditions. After each addition transmittance of the dispersion was measured with a fiberoptic dip probe UV-VIS spectrophotometer.Secondly, dispersions with constantconcentrations of HPMC and SDS were prepared andtheir transmittance was measured with a fiber optic dip probe and in a cuvette. We compared measurements made with both spectrophotometers and also measurements of dispersions with different concentrations of HPMC and SDS. Transmittance of HPMC and SDS dispersions started to decrease at 0.05 % SDS in the dispersion,regardless of the polymer concentration. At higher SDS concentrations, transmittance was even lower and then reached a minimum at some point. With further addition of SDS solution, transmittance began to increase again. At lower HPMC concentrations (0.3 g/L – 2.0 g/L), we observed the formation of a clump at approximately 0.10 % SDS in the dispersion, while at higher concentrations (5.0 g/L – 10.0 g/L) this did not occur, but a very viscous mixture was formed throughout the volume of the dispersion at approximately 0.40 % SDS in the dispersion.Na-DF did not affect transmittance measurements. Dissolution tests of Na-DF from matrix tablets with HPMC were performed using paddle apparatus (Apparatus II) as described in USP in DMB pH 4with addition of SDS in a concentration range from 0.0 to 0.20 w/V %.Addition of SDSto dissolution mediaaccelerated the release of Na-DF from tablets in most cases and only with 0.05 % and 0.07 % of SDS added to DMB, we observed lower % of released active ingredientcompared to DMB. Swelling of tablets was monitored during dissolution tests using a DissoGUARD® camera system. Images of tablets were made before the tests started and at all eight sampling points. We determined diameter and thickness of tablets and calculated relative indexes of diameter and thickness. Swelling at 0.05 % SDS in the direction of both tablet dimensions was greater than at lower and higherconcentrations of SDS in the medium.Tablets were also weighedbefore the dissolution test and after the 4-hour test. The largest weight gain was also found in DMB with 0.05 % SDS. Transmittance of HPMC and SDS dispersions started to decrease at the concentration of 0.05 % SDSin the dispersion,regardless of the polymer concentration. At concentrations of 0.05 % and 0.07 % SDS added to DMB, the release of Na-DF was decreased and swelling of tablets was increased when compared to DMB. This could have happened due to interactions between HPMC and SDS.

• Keywords: SDS-HPMC interactions, turbidity, transmittance, UV-VIS spectrophotometer, fiber optic dip probe, release, swelling of tablets