Izboljševanje raztapljanja ibuprofena iz trdnih disperzij z mezoporoznim silicijevim dioksidom

Knap, Patricija (author), Planinšek, Odon (mentor)

Topnost je pomemben parameter, ki omogoča doseganje zahtevanih koncentracij zdravilne učinkovine v sistemskem obtoku in s tem želenega farmakološkega učinka. Danes obstaja velik delež zdravilnih učinkovin, ki so v vodi praktično netopne, kar farmacevtski industriji predstavlja velik izziv. Učinkovine s slabo topnostjo po biofarmacevtski klasifikaciji uvrščamo v razreda II in IV. V prvega sodi tudi nesteroidni antirevmatik ibuprofen, kateremu smo z izdelavo trdnih disperzij z mezoporoznimi nosilci želeli izboljšati raztapljanje. Z metodo odparevanja topila smo izdelali trdne disperzije z različnimi deleži ibuprofena, uporabili pa smo tri različne nosilce. Uporabljeni nosilci so bili Syloid® 244 FP, Aeroperl® 300 Pharma in Syloid® 244 FP, granuliran z Isomaltom GalenIQ␢ 801. Z diferenčno dinamično kalorimetrijo smo analizirali, kolikšna je največja količina ibuprofena, ki ga lahko naložimo v mezoporozni nosilec, da ta ostane v amorfnem stanju. Določili smo, da je najprimernejši delež vgrajenega ibuprofena 30 % glede na celotno maso trdnih disperzij. Učinkovitost nalaganja ibuprofena smo preverili z UV-VIS sprektroskopijo. Z vidika nadaljnjega rokovanja s trdnimi disperzijami smo preko Carrovega indeksa preverili njihove pretočne lastnosti, prav tako smo izmerili povprečen premer delcev in porazdelitev velikosti delcev. Ugotovili smo, da so za tabletiranje najbolj primerne trdne disperzije ibuprofena z nosilcem Syloid® 244 FP, granuliranim z Isomaltom GalenIQ␢ 801. Iz trdnih disperzij, ki so vsebovale 30 % in 40 % ibuprofena z navedenimi nosilci, smo izdelali tablete s hitrim razpadom in izvedli preskus raztapljanja. Kot medij smo uporabili 0,1 M acetatni pufer s pH 4,5. Profile raztapljanja smo primerjali s profilom raztapljanja njihovih fizikalnih zmesi in čistega ibuprofena. Ugotavljali smo, katera sestava trdnih disperzij (delež ibuprofena in uporabljen nosilec) najbolj pripomore k izboljšanju raztapljanja trdnih disperzij. Tudi tokrat smo najboljše rezultate dobili pri trdnih disperzijah z nosilcem Syloid® 244 FP, granuliranim z Isomaltom GalenIQ␢ 801, s 30 % vsebnostjo ibuprofena.

• Language: Slovenian
• Keywords: trdna disperzija, ibuprofen, mezoporozni silicijev dioksid, amorfizacija učinkovin, topnost, raztapljanje
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2021
• PID: 20.500.12556/RUL-134125
• Publication date in RUL: 24.12.2021

Secondary language

• Language: English
• Title: Improving the dissolution of ibuprofen from solid dispersions with mesoporous silica

Abstract

Solubility is an important parameter that enables the achievement of the required concentrations of the active ingredient in the systemic cyrculation and thus the desired pharmacological effect. Today, there is a large proportion of active ingredients that are practically insoluble in water, which is a major challenge for the pharmaceutical industry. According to the biopharmaceutical classification, substances with low solubility are classified in classes II and IV. The former includes non-steroidal anti-inflammatory drug ibuprofen, which we wanted to improve its dissolution by preparing solid dispersions with mesoporous carriers. Using the solvent evaporation method, solid dispersions with different proportions of ibuprofen were prepared using three different carriers. These were Syloid® 244 FP, Aeroperl® 300 Pharma and Syloid® 244 FP granulated with Isomalt GalenIQ␢ 801. Differential calorimetry was used to determine the maximum amount of ibuprofen that can be loaded into the mesoporous carrier to maintain it in an amorphous state. We found that the most suitable proportion of incorporated ibuprofen is 30% based on the total mass of the solid dispersions. The loading efficiency of ibuprofen was checked by UV-VIS spectroscopy. With regard to further handling of the solid dispersions, we checked their flow properties by Carr index and measured the average particle diameter and particle size distribution. We found that solid dispersions of ibuprofen with carrier Syloid® 244 FP, granulated with Isomalt GalenIQ␢ 801, were the most suitable for tableting. Rapidly disintegrating tablets were prepared from solid dispersions containing 30 % and 40 % ibuprofen with all carriers and a dissolution test was performed. 0,1 M acetate buffer with a pH of 4.5 was used as the medium. The dissolution profiles were compared with the dissolution profiles of their physical mixtures and pure ibuprofen. We determined which composition of the solid dispersions (ibuprofen content and carrier used) contributed most to improving the dissolution of the solid dispersions. Again, the best results were obtained with solid dispersions containing Syloid® 244 FP, granulated with Isomalt GalenIQ␢ 801, with 30% ibuprofen.

• Keywords: solid dispersions, ibuprofen, mesoporous silica, amorphisation of active ingredients, solubility, dissolution