Abstract | Kitozan je hidrofilan, biokompatibilan i biorazgradljiv polimer koji se u zadnjih 20 godina uvelike istražuje kao polimer izbora u pripravi inovativnih terapijskih sustava. Sušenje raspršivanjem predstavlja metodu izbora u izradi praškastih terapijskih sustava temeljenih na kitozanu i njegovim derivatima. Sustavni pristup razvoju kitozanskih mikročestica metodom sušenja raspršivanjem uključuje sveobuhvatnu karakterizaciju ishodnih polimera te polimernih mikročestica pripravljenih preliminarnim sušenjem raspršivanjem, a s ciljem procjene kritičnih procesnih parametara u pripravi suhog produkta.
U ovom radu provedena je fizičko-kemijska karakterizacija kitozana male, srednje i velike molekulske mase te mikročestica pripravljenih preliminarnim sušenjem raspršivanjem odgovarajućih polimernih otopina. Uz kitozane, karakteriziran je i polivinilni alkohol PVA 8-88 (PVA) kao polimer koji može doći u kombinaciji s kitozanom u pripravi mikročestica iz jednostavnih i složenih (emulzijskih) sustava. Kitozanske mikročestice uspješno su pripravljene metodom sušenja raspršivanjem. Korištena konfiguracija uređaja za sušenje raspršivanjem (ultrazvučna sapnica, standardna konusna kolona za sušenje i ciklon srednje veličine) te postavljeni procesni parametri (brzina rada peristaltičke pumpe od 20%, snaga ultrazvučne sapnice 97%, brzina zagrijanog zraka 0,25 m3/min, temperatura zraka na ulasku u kolonu za sušenje 150°C), rezultirali su iskorištenjem procesa od 71,56-84,93%. Proces priprave mikročestica sušenjem raspršivanjem otopine PVA pri istim uvjetima, rezultirao je malim iskorištenjem (29,09%), prvenstveno uslijed relativno niske temperature staklišta PVA (oko 44ºC). Srednji promjer kitozanskih mikročestica kretao se u rasponu od 6,6 ± 2,4 do 9,5 ± 3,6 m, dok su mikročestice PVA karakterizirane veličinom čestica od 11,7 ± 4,1 m. Za sve ispitivane polimere, sadržaj vlage u mikročesticama bio je niži od sadržaja vlage u ishodnim polimerima. Kitozani su higroskopniji od PVA i amorfne strukture, dok je PVA dijelom kristalinične strukture. Sušenje raspršivanjem otopine PVA rezultiralo je dodatnom amorfizacijom polimera. Kitozanske mikročestice su sferičnog oblika i relativno široke raspodjele veličina. Male čestice su naborane površine, dok su velike čestice glatke površine, uz rijetka blaga uvrnuća. Nabori na površini nastali su uslijed smežuravanja mikročestica nakon formiranja čvrste ovojnice. Rezultati provedene karakterizacije ishodnih polimera i mikročestica pripravljenih sušenjem raspršivanjem korisni su za daljnje optimiranje procesa priprave i dizajniranje terapijskog sustava temeljenog na kitozanu. |
Abstract (english) | Chitosan is a hydrophilic, biocompatible and biodegradable polymer that has been extensively investigated over the last 20 years as a polymer of choice in the development of innovative drug delivery systems. Spray-drying is the method of choice in the production of powdered delivery systems based on chitosan and its derivatives. The systematic approach to the development of spray-dried chitosan microparticles involves a comprehensive characterization of the polymers as raw materials and polymeric microparticles prepared by preliminary spray drying with the aim to estimate the critical process parameters in the preparation of the dry product.
In this work physico-chemical characterization of low, medium and high molecular weight chitosan and microparticles prepared by preliminary spray-drying of corresponding polymer solutions, was performed. Besides chitosans, properties of polyvinyl alcohol PVA 8-88 (PVA), the polymer that can be combined with chitosan in the preparation of microparticles from simple and complex (i.e. emulsion) systems, were determined. The chitosan microparticles were successfully prepared by spray drying method. The spray dryer configuration used (ultrasonic nozzle, standard conical drying column and medium-size cyclone) and process parameters employed (peristaltic pump speed of 20%, ultrasonic nozzle strength of 97%, inlet air flow of 0.25 m3/min, inlet air temperature of 150°C) resulted in a process yield ranging from 71.56 to 84.93%. The PVA solution spray-drying under the same conditions resulted in a low yield (29.09%), primarily due to relatively low PVA glass-transition temperature (about 44°C). The mean diameter of chitosan microparticles ranged from 6.6 ± 2.4 to 9.5 ± 3.6 μm, while the size of PVA microparticles was 11.7 ± 4.1 μm. For all polymers tested, the moisture content of the microparticles was lower than the moisture content of the polymers as raw materials. Chitosans were found to be more hygroscopic than PVA and characterised by amorphous structure, while PVA had a partially crystalline-structure. PVA solution spray-drying promoted its amorphisation. Chitosan microparticles ware spherical in shape and had relatively wide size distribution. Small particles had wrinkled surface, while large particles had smooth or slightly curling surface. Wrinkles at the surface of the small particles were caused by shrivelling of the microparticles after the solid crust formation. The results of the performed characterization of the polymers as raw materials and spray-dried polymeric microparticles will be of great use for further optimization of the spray-drying process and chitosan-based drug delivery system design. |