Therapeutically Effective Controlled Release Formulation of Pirfenidone from Nontoxic Biocompatible Carboxymethyl Pullulan-Poly(vinyl alcohol) Interpenetrating Polymer Networks

Abstract

The present study was conducted to develop therapeutically effective controlled release formulation of pirfenidone (PFD) and explore the possibility to reduce the total administered dose and dosing regimen. For this purpose, pH-sensitive biomaterial was prepared by inducing carboxymethyl group on pullulan by Williamson ether synthesis reaction, and further, interpenetrating polymeric network microspheres were prepared by glutaraldehyde-assisted water-in-oil (w/o) emulsion cross-linking method, which showed higher swelling ratio in acidic and basic pH. The formation of microspheres was confirmed by different spectral characterization techniques, and thermal kinetic study indicated the formation of thermally stable microspheres. Cell viability and biocompatibility studies on hepatocellular carcinoma (HepG2) cell showed the polymeric matrix to be biocompatible. In vitro dissolution of optimized formulation (F5) showed releases of 54.09 and 76.37% in 0.1 N HCl after 2 h and phosphate buffer (pH 6.8) up to 8 h, respectively. In vivo performances of prepared microsphere and marketed product of PFD were compared in rabbit. Tmax (time taken to reach peak plasma concentration) was found to be achieved at 0.83 h, compared to 0.5 h for Pirfenex with no significant difference complementing the immediate action, while area under curve was significantly greater for optimized formulation (9768 ± 1300 ng h/mL) compared to Pirfenex (4311 ± 110 ng h/mL), complementing the sustained action. In vivo pharmacokinetic study suggested that the prepared microsphere could be a potential candidate for therapeutically effective controlled delivery of PFD used in dyspnea and cough management due to idiopathic pulmonary fibrosis.

Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment

“…TEM images represented in Figure 3A revealed that the liposomes were of spherical shape with a smooth surface and little to no aggregation, indicating that the vesicles were uniformly dispersed. XRD and DSC results were found to be consistent with earlier studies where a polymeric network of microspheres made of pirfenidone was formulated [45].…”

“…This was in contrast to PFD-D-Lip, which exhibited no peaks, likely due to the amorphous nature of the drug in liposomal formulation ( Figure 3C). Results were found to be consistent with earlier studies of PFD microspheres by Soni et al [45]. The physical mixture of Blank D-Lip and PFD also exhibited peaks inferring to the crystalline nature of the drug.…”

Dual drug-loaded coaxial nanofibers for the treatment of corneal abrasion

“…However, for the pure pirfenidone and moxifloxacin, a very clear characteristic reflection is observed in their XRD pattern. Distinct peaks at 8.90º, 14.94º, 19.04º, 23.08º, 24.80º and 27.60º were observed in pirfenidone diffractogram, which is similar to the findings of Kashikar et al (2014) and Soni et al (2018) pirfenidone diffractograms. The moxifloxacin XRD pattern showed diffraction peaks at 5.90º, 8.62º, 11.81º, 14.48º, 15.58º, 17.34º, 24.18º, 26.60º, 27.46º and 31.54º, which are in agreement with the moxifloxacin XRD pattern of Mudgil and Pawar (2013).…”

“…The FTIR spectrum for pirfenidone demonstrated stretching at 3050 cmˉ¹ (aromatic C-H stretching), 2929 cmˉ¹ (aliphatic C-H stretching), 1671 cmˉ¹ (C=O stretching in tertiary amide), 1622-1454 cmˉ¹, (aromatic C=C and pyridine ring stretching) and 1273-1260 cmˉ¹ (C-N stretching), which is similar to the pirfenidone FTIR spectrum of Soni et al (2018). In addition, sharp bands between 824 cmˉ¹ and 699 cmˉ¹ are present in the fingerprint region that represent substitutions in the benzene ring.…”

Biomaterial-based immunoengineering to fight COVID-19 and infectious diseases

“…In one approach, the encapsulation of pirfenidone within modular interpenetrating polymeric network microspheres is sufficient to achieve a more therapeutically desired controlled release profile following oral delivery, compared with the clinically available Pirfenex. 141 In another example, the internasal delivery of IL-10 via hyaluronan and heparin-based hydrogels further decreases inflammatory and fibrotic markers in a bleomycin-induced pulmonary fibrosis mouse model, compared with the delivery of IL-10 alone. This formulation combines the biocompatibility and biodegradability of hyaluronan with the ability of heparin to bind IL-10 to enhance stability and extend the release rate.…”