Izdelava trdnih disperzij fenofibrata s koprocesirano pomožno snovjo in stiskanje orodisperzibilnih tablet

Perko, Mark (author), Planinšek, Odon (mentor)

Fenofibrat spada med fibrate in ga uporabljamo za zniževanje povišane količine lipidov v krvi. Spada med težko topne zdravilne učinkovine, ki jih po biofarmacevtski klasifikaciji uvrščamo v razred II. Učinkovini smo želeli izboljšati topnost s pomočjo izdelave trdne disperzije s koprecirano pomožno snovjo. Kot nosilec za izdelavo trdnih disperzij smo uporabili silicijev dioksid (Syloid), ki je široko uporabljana pomožna snov pri izdelavi tablet. Ima slabo pretočnost in stisljivost, zato smo jo koprocesirali z eritritolom. Izdelali smo različne granulate, pri katerih smo uporabili različno količino izopropanola za razprševanje, v vseh pa dodali razmerje eritrotol-a in Syloid-a 1:4. Trdne disperzije fenofibrata smo pripravili z metodo odparevanje topila. Izdelali smo trdne disperzije, ki so vsebovale 10 %, 20 %, 30 % in 40 % učinkovine. Te smo vrednotili z različnimi metodami za določanje velikost delcev, specifične površine, trdnosti izdelanih tablet ter sproščanje. Slednjega smo izvedli v fosfatnem pufru pH = 6.8 z dodatkom natrijev lavril sulfata. Zanimalo nas je, katera od izdelavnih trdnih disperzij je najbolj primerna za izdelavo orodisperzibilne tablete. Pripravljenim granulatom smo dodali Ac-Di-Sol in izdelali orodisperzibilne tablete, ki smo jih vrednotili glede na razpadlosti ter sproščanja učinkovine. Ugotovili smo, da pripravljene trdne disperzije izkazujejo izboljšajo raztapljanje fenofibrata v primerjavi s fizikalnimi zmesmi. Eritritol v koprocesirani pomožni snovi predstavlja vezivo, poslabša sproščanje učinkovine. Na podlagi zbranih rezultatov smo ugotovili, da je najbolj primerna formulacija za izdelavo orodisperzibilne tablete, ta, ki vsebuje 30 % trdne disperzije pripravljene z granulatom, ki je vseboval 90 % izopropanola.

• Language: Slovenian
• Keywords: fenofibrat, trdna disperzija, syloid, eritritol, raztapljanje
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2022
• PID: 20.500.12556/RUL-143246
• Publication date in RUL: 09.12.2022

Secondary language

• Language: English
• Title: Production of fenofibrate solid dispersions with co-processed excipient and compression of orodispersible tablets

Abstract

Fenofibrate is drug of the fibrate class used to treat abnormal blood lipid levels. It is a poorly soluble active substance, belonging to class II of the biopharmaceutical classification. We wanted to improve the solubility of the active substance by making a solid dispersion in a co-processed excipient. In the Master's thesis, we studied solubility of fenofibrate and prepared different solid dispersions containing 10 %, 20 %, 30 % and 40 % of the API. Syloid, which contains silicon dioxed and it is a widly used as excipient in pharmacy. Since, it has a poor flow and also poor compressibility, we added in the formulation excipient erythritol. Different granules were made using different amounts of isopropanol for dispersion and we added in all of them a ratio of erythrotol to Syloid 1:4. The solid dispersions were prepared by using the evaporatation method. We used the different methods to determine particle size, specific surface area, different hardness at different compression forces and dissolution. The latter was carried out in phosphate buffer pH = 6.8 with the addition of sodium lauryl sulphate, where different amounts of the incorporated active substance were analysed. We were interested in which of the solid dispersions was the most suitable for the production of the orodispersible tablet. Additionlly, we compared the results of the prepared solid dispersions. The hardness of the prepared tablets was measured. The prepared orodispersible tablets were added to Ac-Di-Sol and evaluated in the disintegration test and the disolution test. Results of orodispersible tablet were compared with other results from previous dissolution test measurement. Finally, we conclued that there are numerous factors that affect the rate and speed of relase. These factors are hardness of the formulation, the amount of API in it, the amount of isopropanol added at the granulation phase, the amout of erythritol added in the formulation, the characteristics of the coprocessed carrier used… Furthermore, we found that the prepared solid dispersions show improved dissolution compared to physical mixtures. At the same time, erythritol in the formulation slightly reduces the dissolution of the active substance. Based on the results obtained, we concluded that the most suitable formulation for the development of a orodispersible tablet is one containing 30% solid dispersion prepared with granulate, which containing 90 % izopropanol.

• Keywords: fenofibrate, solid dispersion, syloid, erythritol, dissolution