Proučevanje vpliva magnezijevega stearata na fizikalne lastnosti tablet in sproščanje zdravilne učinkovine : enoviti magistrski študijski program Farmacija

Štekar, Ana Carolina (author), German Ilić, Ilija (mentor), Stanić Ljubin, Tijana (comentor)

Magnezijev stearat se kot pomožna snov nahaja v več kot polovici tabletnih formulacij.Najpogosteje ga uporabljamo kot mazivo in antiadheziv, izboljša pa tudi pretok prahov in zrnc. Ob njegovi neprevidni uporabi lahko podaljšamo čas razpadnosti tablet in upočasnimo sproščanje zdravilne učinkovine iz tablete. Ta dva pojava sta posledici večje obdanosti delcev zmesi za tabletiranje z magnezijevim stearatom, ki je izrazito hidrofobne narave, zato prepreči močenje površine tablete z vodo. Z magnezijevim stearatom pa lahko negativno vplivamo tudi na mehanske lastnosti tablet, saj med stiskanjem tablet prepreči tvorbo močnejših povezav med delci tabletne zmesi.Obseg vmešanosti magnezijevega stearata v zmes za tabletiranje je odvisen od njegovih fizikalno-kemijskih lastnosti in njegove količine, pa tudi lastnosti delcev pomožnih snovi ali zrnc in pogojev mešanja tabletne zmesi. Proučili smo fizikalne lastnosti dveh magnezijevih stearatov in ugotovili, da se surovini različnih proizvajalcev med seboj precej razlikujeta v specifični površini, porazdelitvi velikosti delcev, morfologiji delcev, urejenosti kristalne strukture, hidratni obliki in deležu polarnega prispevka k prosti površinski energiji. Te lastnosti pomembno vplivajo na učinkovitost obdajanja delcev zmesi za tabletiranje z magnezijevim stearatom.V magistrski nalogi smo prišli do ugotovitve, da daljši čas vmešavanja magnezijevega stearata v laboratorijskem mešalniku podaljša čas razpadnosti tablet in poveča krušljivost tablet. Vpliva na zmanjšano trdnost tablet nismo zaznali. Poleg tega na vmešanje magnezijevega stearata pomembno prispeva tudi vrtenje vetrnic polnilnega sistema rotirke. Daljši kot je čas zadrževanja tabletne zmesi v polnilnem sistemu, daljši je čas razpadnosti tablet in počasnejše se zdravilna učinkovina sprošča iz tablete. Poveča pa se tudi krušljivost tablet. S pomočjo načrtovanja eksperimentov smo proučili tudi, kako vpliva hitrost vrtenja vetrnic polnilnega sistema na lastnosti tablet. Prišli smo do zaključka, da se čas razpadnosti značilno podaljša, če se vetrnice vrtijo hitreje. Vpliv hitrosti vrtenja vetrnic polnilnega sistema smo potrdili tudi na industrijskem nivoju tabletiranja pri višjih hitrostih tabletiranja.

• Language: Slovenian
• Keywords: tablete pomožne snovi magnezijev stearat lubrikacija hidrofobizacija vetrnice polnilnega sistema
• Work type: Master's thesis/paper
• Typology: 2.09 - Master's Thesis
• Organization: FFA - Faculty of Pharmacy
• Place of publishing: Ljubljana
• Publisher: [A. C. Štekar]
• Year: 2018
• Number of pages: IX, 67 f., I-III f. pril.
• PID: 20.500.12556/RUL-120362
• UDC: 661.12:661.846(043.3)
• COBISS.SI-ID: 4641137
• Publication date in RUL: 18.09.2020

Secondary language

• Language: English
• Title: Investigation of the effect of magnesium stearate on tablets0 physical properties and drug erlease

Abstract

Magnesium stearate is present as an excipient in more than half of tablet formulations. Most frequently it has a lubricant or antiadherent function, and at the same time it improves flow properties of tableting blends. If magnesium stearate is not used carefully, it can prolong tablet disintegration time and retard dissolution profile. This is caused by overlubrication effect which means that particles of tableting blend are overly coated with magnesium stearate. Due to its high hydrophobicity, magnesium stearate hinders wettability of tablet surface with water. Magnesium stearate can also have deleterious effects on mechanical strength of tablets, since it prevents the formation of strong bonds during compaction. Lubrication potential of magnesium stearate depends on its physico-chemical properties, its quantity in tableting blend, properties of substrate particles, and mixing conditions of the tableting blend. In this master thesis the physico-chemical properties of two magnesium stearate batches from different manufacturers were studied. We discovered that they differ in specific surface area, particle size distribution, particle morphology, degree of cristallinity, pseudopolymorphism and in polar component of free surface energy. These properties have a significant impact on the efficacy of lubrication. The results of this master thesis show that the disintegration time extends and the friability of tablets increases with longer mixing time of magnesium stearate into the tableting blend on laboratory scale. The effect on reduction of tablet hardness was not observed. Furthermore, the mixing of magnesium stearate into the tableting blend occurs also in the force feeder of a rotary tablet press because of the rotating paddles. Longer residence time of tableting blend in a force feeder leads to longer disintegration time of a tablet and slower dissolution profile. Friability of tablets in this case increases.Lastly, we used Design of Experiment to study the effect of force feeder paddles' rotation speed on tablet properties. The disintegration time is significantly longer if the paddles rotate faster. This effect was further confirmed on the industry scale tablet press where higher tableting speeds were used.

• Keywords: Magnesium stearate lubricant lubrication hydrophobisation force feeder paddles