TY - JOUR
T1 - A Micro-Configured Multiparticulate Reconstitutable Suspension Powder of Fixed Dose Rifampicin and Pyrazinamide
T2 - Optimal Fabrication and In Vitro Quality Evaluation
AU - Rampedi, Penelope N.
AU - Ogunrombi, Modupe O.
AU - Wesley-Smith, James
AU - Adeleke, Oluwatoyin A.
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2023/1
Y1 - 2023/1
N2 - 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.
AB - 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.
KW - antitubercular
KW - design of experiments
KW - dosage form
KW - dry suspension
KW - multiparticulate drug carrier
KW - oral drug delivery
KW - paediatric
KW - pharmaceutical formulations
KW - tuberculosis
UR - http://www.scopus.com/inward/record.url?scp=85146780406&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics15010064
DO - 10.3390/pharmaceutics15010064
M3 - Article
C2 - 36678693
AN - SCOPUS:85146780406
SN - 1999-4923
VL - 15
JO - Pharmaceutics
JF - Pharmaceutics
IS - 1
M1 - 64
ER -
