A Micro-Configured Multiparticulate Reconstitutable Suspension Powder of Fixed Dose Rifampicin and Pyrazinamide: Optimal Fabrication and In Vitro Quality Evaluation

Abstract

The scarcity of age-appropriate pharmaceutical formulations is one of the major challenges impeding successful management of tuberculosis (TB) prevalence in minors. To this end, we designed and assessed the quality of a multiparticulate reconstitutable suspension powder containing fixed dose rifampicin and pyrazinamide (150 mg/300 mg per 5 mL) which was prepared employing solid–liquid direct dispersion coupled with timed dehydration, and mechanical pulverization. The optimized formulation had a high production yield (96.000 ± 3.270%), displayed noteworthy powder flow quality (9.670 ± 1.150°), upon reconstitution the suspension flow property was non-Newtonian and was easily redispersible with gentle manual agitation (1.720 ± 0.011 strokes/second). Effective drug loading was attained for both pyrazinamide (97.230 ± 2.570%w/w) and rifampicin (97.610 ± 0.020%w/w) and drug release followed a zero-order kinetic model (R2 = 0.990) for both drugs. Microscopic examinations confirmed drug encapsulation efficiency and showed that the particulates were micro-dimensional in nature (n < 700.000 µm). The formulation was physicochemically stable with no chemically irreversible drug-excipient interactions based on the results of characterization experiments performed. Findings from organoleptic evaluations generated an overall rating of 4.000 ± 0.000 for its attractive appearance and colour 5.000 ± 0.000 confirming its excellent taste and extremely pleasant smell. Preliminary cytotoxicity studies showed a cell viability above 70.000% which indicates that the FDC formulation was biocompatible. The optimized formulation was environmentally stable either as a dry powder or reconstituted suspension. Accordingly, a stable and palatable FDC antimycobacterial reconstitutable oral suspension powder, intended for flexible dosing in children and adolescents, was optimally fabricated.

Nanotechnological innovations in paediatric tuberculosis management: current trends and future prospects

“…The optimised product was a reddish-brown, easily flowing, finely structured powder that showed optimal reconstitution and settling characteristics when mixed in an aqueous solution. The new drug-loaded suspension formulation had no substantial adverse effect on the model cells (HepG2) tested and was possibly biocompatible (Rampedi et al, 2022b).…”

“…Due to their ongoing development, paediatric patients need a variety of oral drug delivery systems compared to other demographic groups, which has implications for dose and administration. Oral drug administration, such as liquids or dispersible tablets is convenient, economical, and safe for treatment in children (Rampedi et al, 2022a). Since conventional formulations were not created for this patient population, compounding and manipulation have become standard procedures.…”

Nanofibrous scaffolds for the healing of the fibrocartilaginous enthesis: advances and prospects

“…5,8 When a sudden load is applied in the direction of muscle stress, the tensile performance of the tendon end is better than that of the bone end. 30 The natural healing process of the fibrocartilaginous enthesis is complex and can be divided into three stages: inflammation (0-7 days), rapid proliferation (5-14 days), and gradual remodeling (414 days). 8 Fibrocartilaginous enthesis healing is typically usually achieved by the formation of disorganized fibrovascular scar tissue rather than natural gradient tissue regeneration.…”

“…The materials most commonly used for nanofibrous scaffolds are polymers, which can be classified as natural or synthetic polymers according to their source. 30,95 Natural polymers include fibroin, gelatin, collagen, and chitosan, which have excellent biocompatibility and biodegradability in common, and are conducive to cell proliferation, adhesion, and differentiation. 34 However, natural polymers have poor mechanical properties and often need to be used with synthetic polymers.…”

“…Its large surface area-to-volume ratio can effectively promote cell adhesion, proliferation, differentiation, and drug loading. 29,30 In recent years, nanofibrous scaffolds have been widely used in the field of tissue engineering. [31][32][33][34][35][36] The morphology of nanofibrous scaffolds is easy to adjust, as it appears that simulating the composition and structure of fibrocartilaginous enthesis is more beneficial to its regeneration and improving the mechanical properties of tissues.…”