Priprava in Hecklova analiza nove koprocesirane pomožne snovi Harke Plus Tab Prime A

Grošelj, Luka (avtor), Srčič, Stanko (mentor)

Razvoj trdnih farmacevtskih oblik stremi k poenostavitvi in pocenitvi proizvodnje tablet z direktnim stiskanjem, kar zahteva ustrezne lastnosti zmesi: dobro pretočnost in stisljivost. Bistven vpliv pri tem imajo uporabljene pomožne snovi, ki jih lahko s predhodno obdelavo, tj. koprocesiranjem, medsebojno povežemo, zagotovimo sinergijo komponent in tako izboljšamo lastnosti, pomembne za tabletiranje. Iz fizikalne zmesi treh pomožnih snovi, imenovane Harke Plus Tab Prime, smo z metodo vrtinčnoslojne granulacije in dvovijačne vlažne ekstruzije pripravili vzorce koprocesirane pomožne snovi. Tako izdelanim pomožnim snovem smo ovrednotili pretočnost, porazdelitev velikosti delcev, njihovo morfologijo in stisljivost ter jih primerjali z izhodno fizikalno zmesjo in komercialno dostopnima koprocesiranima snovema: Granfiller D in Hisorad. Pretočnost smo ocenili s Hausnerjevim razmerjem in Carrovim indeksom, stisljivost pa z določanjem kompresibilnosti in kompaktibilnosti preko Hecklove analize. Ugotovili smo, da ima koprocesiranje večji vpliv na kompaktibilnost, medtem ko je vpliv na kompresibilnost in elastičnost zelo majhen in sta ti lastnosti predvsem odvisni od sestave materiala. Vzorci, koprocesirani z ekstruzijo, so dosegali najboljšo pretočnost, a so imeli zelo široko, bimodalno porazdelitev velikosti. Pri višjih obratih polža in večjem deležu uporabljene vode so nastajali večji delci, ki so imeli tudi slabšo stisljivost. Koprocesiranje z vrtinčnoslojno granulacijo bistveno ne izboljša pretočnosti, zagotavlja pa ozko unimodalno porazdelitev velikosti in stisljivost, primerljivo s stisljivostjo izhodne fizikalne zmesi. Praktično uporabnost koprocesiranja izhodnega materiala z vrtinčnoslojno granulacijo smo potrdili s testom enakomernosti mase tablet s 30-, 45- in 60-odstotno vsebnostjo paracetamola kot modelne učinkovine. Kljub temu, da izboljšave fizikalnih lastnosti, ki smo jih dosegli s transformacijo zmesi Harke Plus Tab Prime v koprocesirano pomožno snov, niso značilne, smo z opravljenim raziskovalnim delom pridobili pomembne izkušnje za nadaljnji razvoj koprocesiranja z metodo vrtinčnoslojne granulacije in dvovijačne vlažne ekstruzije.

• Jezik: Slovenski jezik
• Ključne besede: koprocesirana pomožna snov, vrtinčnoslojna granulacija, vlažna ekstruzija, Hecklova analiza, pretočnost, kompresibilnost, kompaktibilnost
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2022
• PID: 20.500.12556/RUL-136027
• Datum objave v RUL: 08.04.2022

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Preparation and Heckel analysis of new Co-Processed excipient Harke Plus Tab Prime A

Izvleček

The development of solid pharmaceutical forms aims to simplify and reduce the cost of production of tablets by direct compression, which requires the appropriate properties of the mixture: good flowability and compressibility. The excipients used have a significant influence over this. Some can be pre-treated by coprocessing that interconnects particles and ensures synergy of components and thus improve properties important for tableting. Samples of the coprocessed excipient were prepared from a physical mixture of three excipients called Harke Plus Tab Prime using the fluid bed granulation and twin-screw wet extrusion method. Prepared coprocessed excipients were evaluated for flowability, particle size distribution, their morphology and compressibility, and compared with the starting physical mixture and commercially available coprocessed substances: Granfiller D and Hisorad. Flowability was estimated by the Hausner ratio and the Carr’s index while compressibility and compatibility were determined through Heckel analysis. We found that coprocessing has a greater impact on compatibility, while the impact on compressibility and elasticity is very small and these properties mainly depend on the composition of the material. Samples co-processed by extrusion achieved the best flowability, but had a very wide, bimodal size distribution. At higher screw speeds and at higher proportion of water used, larger particles were formed, but had poorer compressibility. Coprocessing by fluid bed granulation does not significantly improve flowability but provides a narrow unimodal size distribution and compressibility comparable to the original physical mixture. The practical applicability of coprocessing the original material with fluidized bed granulation was confirmed by a test of uniformity of mass for tablets with 30%, 45% and 60% content of paracetamol as a model active ingredient. Although the improvements in physical properties achieved by transforming Harke Plus Tab Prime into a coprocessed excipient are not significant, our research work gained significant experience for further development of coprocessing excipients by fluidized bed granulation and twin-screw wet extrusion.

• Ključne besede: coprocessed excipient, fluid bed granulation, wet extrusion, Heckel analysis, flowability, compressibility, compatibility