| Abstract | Sušenje raspršivanjem tehnološki je postupak koji nalazi široku primjenu u razvoju lijekova. Optimiranjem procesnih parametara moguće je pripraviti praškasti produkt kontroliranih svojstava čestica. Postupak je uvelike primjenjiv u razvoju inovativnih terapijskih sustava željenog profila oslobađanja uklopljenog lijeka. Česti problemi vezani uz oblikovanje lijekova postupcima sušenja su previsok sadržaj vlage zaostale nakon proizvodnog procesa te nakupljanje vlage prilikom skladištenja, pogotovo u slučaju izrazito higroskopnih produkata.
Cilj ovog rada bio je pripraviti alginatne mikročestice metodom sušenja raspršivanjem te ispitati utjecaj brzine dotoka uzorka i protoka medija za sušenje (kroz postavku rada aspiratora) na iskorištenje procesa, veličinu čestica i sadržaj ostatne vlage u produktu. Korišten je puni faktorijalni dizajn eksperimenta sa tri razine procesnih parametara (brzina dotoka uzorka od 2,12, 3,92 i 5,64 g/min te kapacitet rada aspiratora od 25, 50 i 75 %). Otopina natrijevog alginata (0,5 %, m/V) sušena je raspršivanjem pri ulaznoj temperaturi od 140°C i protoku komprimiranog zraka od 700 Nl/h korištenjem uređaja s bifluidom sapnicom. Veličina čestica određena je mikroskopskom analizom slike. Sadržaj vlage u osušenim produktima određen je termogravimetrijskom analizom. Iskorištenje procesa kretalo se u rasponu od 40,19 do 59,57%. Uočen je značajan utjecaj variranih parametara na iskorištenje procesa: povećanje brzine protoka uzorka rezultiralo je njegovim smanjenjem, dok je povećanje kapaciteta aspiratora uzrokovalo veće iskorištenje. Srednji promjer alginatnih mikročestica kretao se u rasponu od 2,80±0,04 μm do 3,14±0,17 μm. Navedenom metodom nije bilo moguće precizno odrediti veličinu čestica zbog adhezije manjih čestica na veće te zbog aglomeriranja čestica. Sadržaj vlage alginatnih mikročestica kretao se u rasponu od 9,75 do 11,51 %. Nije uočena ovisnost sadržaja vlage o promatranim parametrima. Relativno velik sadržaj vlage u mikročesticama objašnjen je adsorpcijom atmosferske vlage na alginatne mikročestice nakon procesa sušenja. Provedeno ispitivanje međuovisnosti procesnih parametara i svojstava suhog produkta može poslužiti u razvoju alginatnih terapijskih sustava pripravljenih sušenjem raspršivanjem. |
| Abstract (english) | Spray-drying is a technological process that is widely used in the development of pharmaceuticals. By optimizing the process parameters, it is possible to obtain the powdered product of controlled particle properties. The procedure is largely applicable in the development of innovative drug delivery systems of the desired release profile of the drug. Frequent issues with drug formulation by use of drying processes are too high residual moisture content and the problem of moisture adsorption during storage, especially in the case of highly hygroscopic products.
The aim of this work was to prepare alginate microparticles by spray-drying method and to investigate the influence of the feed rate and drying air flow rate (through aspirator setting) on the process yield, particle size and residual moisture content of the product. A full factorial experimental design with three levels of process parameters was used (sample flow rate of 2.12, 3.92 and 5.64 g/min, and aspirator setting of 25, 50 and 75% of full capacity). The sodium alginate solution (0,5%, w/V) was spray-dried at an inlet temperature of 140°C and a compressed air flow of 700 Nl/h using a bifluid nozzle device. Particle size was determined by microscopic image analysis. Moisture content in dried products was determined by thermogravimetric analysis. The yield of the spray-drying process ranged from 40.19 to 59.57%. Significant influence of the investigated parameters on the process yield was noted: increasing sample flow rate resulted in reduced process yield, while the increase of drying air flow rate caused a greater yield of the process. The mean diameter of alginate microparticles ranged from 2.80±0.04 μm to 3.14±0.17 μm. It was not possible to precisely determine the particle size using this method due to the adhesion of smaller particles to larger ones and due to the agglomeration of the particles. The moisture content of the alginate microparticles ranged from 9.75 to 11.51%. The relationship between the microparticle moisture content and the studied parameters was not observed. Relatively high moisture content in the spray-dried products was explained by adsorption of the atmospheric moisture on alginate microparticles after the spray-drying process. This study on relationship between the process parameters and the properties of the spray-dried product can serve as a starting point in the development of alginate based drug delivery systems prepared by spray-drying. |
