| Abstract | Cilj istraživanja:
Cilj ovog rada bio je istražiti tehnike oblikovanja i farmaceutske oblike probiotičkih pripravaka, probiotika, odnosno skupiti saznanja u izradi formulacija i kompletnom razvoju tih proizvoda. Također, cilj rada je bio na temelju prikupljenih podataka opisati postojeće procese u razvoju farmaceutskih oblika probiotika, dosadašnja saznanja o potencijalnim poteškoćama prilikom razvoja formulacije ili samog oblika, kao i buduće izazove u razvoju farmaceutskih oblika probiotika.
Materijali i metode:
U literaturnoj pretrazi su korištene konstruktivne sintakse kako bi se identificirali potencijalni probiotički proizvodi, tehnologije oblikovanja, farmaceutski oblici i razvoj formulacija. Ciljana pretraga provedena je na bazama MEDLINE/PubMed, Science Direct, Google pretraživaču, putem znanstvenih članaka te dostupnim dokumentima proizvođača i pretraživanjem patenata. Literaturni pregled obuhvaća razdoblje do studenog 2015. i oslanja se na javnodostupne baze.
Rezultati:
Najrazvijenije tehnike oblikovanja mikroorganizama su: liofilizacija (Freeze drying), sušenje raspršivanjem (Spray-drying), hlađenje raspršivanjem (Spray-cooling), fluid-bed aglomeracija i oblaganje u vrtložnom sloju (Fluid-bed agglomeration and Fluid-bed coating) ,sušenje u vakuumu (Vacuum-drying), oblaganje kompresijom (Compression coating), ekstruzijska tehnika za mikrokapsuliranje u mikrosfere (Extrusion techniques for the microencapsulation in microspheres), adhezija na škrobne granule (Adhesion to the starch granules) i metode na bazi emulzija (Emulsion-based techniques). Kao najveći izazov u razvoju formulacija potrebno je premostiti nepovoljne uvjete u probavnom sustavu, nizak pH želučanog sadržaja, prisutnost žučnih soli i enzima gušterače, oslobađanje na ciljanom mjestu djelovanja i osigurati što veći broj preživjelih mikroorganizama. Odabirom odgovarajućih ekscipijensa prilikom oblaganja i razvoja formulacije osiguravamo sigurnu dostavu i stabilnost formulacije od procesa proizvodnje, tijekom skladištenja pa sve do dostave u kolon.
Zaključak:
S tehnološke strane gledano, izazov u oblikovanju i proizvodnji probiotika leži u činjenici što su to živi organizmi, osjetljivi na određene uvjete i parametre u proizvodnji, skladištenju i dostavi na ciljano mjesto djelovanja. Nove tehnologije oblikovanja probiotika omogućuju bolju zaštitu samih bakterija prilikom procesa proizvodnje i izrade formulacija, a posebno pri prolasku kroz probavni sustav (nepovoljni utjecaj niskog pH, žučnih soli i enzima gušterače). Veliki broj patenata u području oblikovanja probiotičkih proizvoda ukazuje nam na napredak i inovativnost u razvoju takvih proizvoda. Posebnu pozornost treba obratiti na funkciju probiotika kao nosača cjepiva (antigena) i njihovu mogućnost imunizacije. |
| Abstract (english) | Objectives:
The main objective of this study was to investigate: i) techniques of developing; ii) available pharmaceutical forms of probiotics; and iii) get insight into the literature knowledge present in the development of formulations and complete development of products containing probiotic bacteria. Additionally, data were collected to describe the ongoing processes in the development of pharmaceutical forms of probiotics; current knowledge about potential issues in the development of the formulation mainly related to the probiotic delivery systems and associated future challenges.
Materials and methods:
In this investigation were used constructive syntaxes to identify potential probiotic products, formulation technology, pharmaceutical forms and formulation development. Targeted literature search was done on MEDLINE / PubMed, Science Direct, Google search engine, articles in the research journals, available documents of manufacturers and patents. The database searching of the scientific literature includes period up to November 2015.
Results:
The most developed techniques of stabilizing and developing products containing live microorganisms are: lyophilization (freeze drying), spray drying, spray cooling, a fluid-bed agglomeration and fluid-bed coating, vacuum drying, compression coating, extrusion techniques for the microencapsulation in microspheres, the adhesion to the starch granules and emulsion-based techniques. The greatest challenge in the development of specific formulation is to design the product which will be able to overcome the unfavorable conditions in the digestive system (associated with low pH of gastric fluid, the presence of bile salts, pancreatic enzymes) and assure precise action of viable microorganisms at the targeted site. By selecting suitable excipients in the course of coating and developing formulations one can provide safe delivery and formulation stability during entire manufacturing process, storage and promote successful delivery in colon.
Conclusion:
From the technological point of view, the challenge associated with the probiotics is the fact that they are living organisms, vulnerable to certain conditions during production, storage and delivery to the target site of action in gut. New technologies of developing probiotics formulation provide better protection of the probiotic bacteria during the manufacturing process and formulation development, especially while passing through the digestive system unfavorable conditions such low pH of gastric fluids, presence of bile salts and pancreatic enzymes may occur. A large number of patents in the field of design of probiotic products and formulations show us the progress and innovation in the development of such products. Special attention should be paid to the function of probiotics as vaccines (antigens) carriers and their ability to be used for the purposes of immunization. |
