Polymeric particles for controlled release of isoniazid and rifampicin

MARÍA ROCÍO PEVERENGO; LUDMILA N. TURINO; FEDERICO KARP; JULIO A LUNA; LUCIANO N. MENGATTO

Rosario

Otro; 7ma Reunión Internacional de Ciencias Farmacéuticas (RICiFa 2023); 2023

Comité Organizador RICIFA

Isoniazid (H) and rifampicin (R) are the two most important antibiotics used in the treatment of tuberculosis (TB). R is unstable in acidic medium and when it is found in formulations combined with H it is even more unstable. Compartmental controlled release systems would not only solve stability issues, but also would reduce the number of doses and side effects during TB treatment; which requires multiple daily drugs for long periods of time. In the present work, particle-based systems for the dual release of H and R were considered. Poly(lactic- co - glycolic) acid (PLGA) was used for the preparation of microparticles (MP) and nanoparticles (NP) by the emulsion/evaporation method. In addition, chitosan (CHT) and bovine gelatin (GEL) were used for the preparation of MP by spray drying. The systems were: 1) PLGA/R MP combined with GEL/CHT/H MP, 2) GEL/CHT/H MP included in PLGA/R MP and 3) PLGA/R NP included in GEL/CHT/H MP. The encapsulation efficiency of R was greater than 50 % in PLGA/R MP and in system 2. The release of R was controlled by the properties of the formulation and the pH of the medium. In the GEL/CHT/H MP the encapsulation efficiency of H was greater than 80 % and was not affected by the inclusion of the NP in system 3. On the other hand, in system 2 the efficiency was 21 % and during in vitro assays the release of H was not observed. From system 3, the 85 % of H was released in the first 2 hours, indicating a rapid initial delivery. In the same period of time, the 35 % of R was released. System 3 showed a better ability to control the release of H and R in comparison with system 1, particularly for R. Microscope observation showed spherical geometry with few pores and a size distribution between 10 - 20 μm for the PLGA/R MP and system 2. The drug-polymer interactions were studied using IR spectroscopy, being the spectra of the formulations similar to that of PLGA even when the MP were macroscopically reddish-brown in color resembling the reactant R. The GEL/CHT/H MP and particles of system 3 presented a spherical and irregular shape with a diameter between 3,0 and 5,8 µm. The IR spectra of GEL/CHT/H MP showed peaks related to GEL, CHT and the drug. On the other hand, the spectrum of system 3 (MP that include PLGA/R NPs), presented peaks corresponding to GEL, CHT and PLGA; however, neither H nor R peaks were observed. In general, for the 3 systems, the similarity between the IR spectra of the particles and the polymers may be due to the fact that they are the major components of the mixture. Using IR spectroscopy, main drug-polymer interactions were not observed. The absence of H release from system 2 can be explained taking into consideration that the drug is located in the internal aqueous phase. The gradual degradation/erosion of PLGA particles during the assay delays the arrival of the drug from the inside of the matrix up to the release medium. In summary, both drugs were released from systems 1 and 3. Particularly, system 3 is interesting for subsequent optimization because both antibiotics are included in the same particle.