TY - JOUR
T1 - Optimal design, characterization and preliminary safety evaluation of an edible orodispersible formulation for pediatric tuberculosis pharmacotherapy
AU - Matawo, Nyaradzo
AU - Adeleke, Oluwatoyin A.
AU - Wesley-Smith, James
N1 - Funding Information:
Acknowledgments: The authors thank the National Centre for Nano-structured Materials, Council for Scientific and Industrial Research, Pretoria, South Africa and the Preclinical Drug Development Platform, North-West University, Potchefstroom, South Africa for sample characterization and cytotoxicity testing respectively. We are grateful to Chantelle Baker from the SMU Electron Microscopy Unit, Pretoria, South Africa for her valuable advice and discussions.
Funding Information:
Funding: This work was funded by the South African National Research Foundation (Grant Number: 113143) and Sefako Makgatho Health Sciences University-DHET Research Development Grant (Grant Number: D112-RDG).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/8/2
Y1 - 2020/8/2
N2 - The severity of tuberculosis (TB) in children is considered a global crisis compounded by the scarcity of pharmaceutical formulations suitable for pediatric use. The purpose of this study was to optimally develop and evaluate a pyrazinamide containing edible orodispersible film formulation potentially suitable for use in pediatrics actively infected with TB. The formulation was prepared employing aqueous-particulate blending and solvent casting methods facilitated by a high performance Box Behnken experimental design template. The optimized orodispersible formulation was mechanically robust, flexible, easy to handle, exhibited rapid disintegration with initial matrix collapse occurring under 60 s (0.58 ± 0.05 min ≡ 34.98 ± 3.00 s) and pyrazinamide release was controlled by anomalous diffusion coupled with matrix disintegration and erosion mechanisms. It was microporous in nature, light weight (57.5 ± 0.5 mg) with an average diameter of 10.5 mm and uniformly distributed pyrazinamide load of 101.13 ± 2.03 %w/w. The formulation was physicochemically stable with no evidence of destructive drug–excipient interactions founded on outcomes of characterization and environmental stability investigations. Preliminary inquiries revealed that the orodispersible formulation was cytobiocompatible, palatable and remained intact under specific storage conditions. Summarily, an edible pyrazinamide containing orodispersible film formulation was optimally designed to potentially improve TB pharmacotherapy in children, particularly the under 5 year olds.
AB - The severity of tuberculosis (TB) in children is considered a global crisis compounded by the scarcity of pharmaceutical formulations suitable for pediatric use. The purpose of this study was to optimally develop and evaluate a pyrazinamide containing edible orodispersible film formulation potentially suitable for use in pediatrics actively infected with TB. The formulation was prepared employing aqueous-particulate blending and solvent casting methods facilitated by a high performance Box Behnken experimental design template. The optimized orodispersible formulation was mechanically robust, flexible, easy to handle, exhibited rapid disintegration with initial matrix collapse occurring under 60 s (0.58 ± 0.05 min ≡ 34.98 ± 3.00 s) and pyrazinamide release was controlled by anomalous diffusion coupled with matrix disintegration and erosion mechanisms. It was microporous in nature, light weight (57.5 ± 0.5 mg) with an average diameter of 10.5 mm and uniformly distributed pyrazinamide load of 101.13 ± 2.03 %w/w. The formulation was physicochemically stable with no evidence of destructive drug–excipient interactions founded on outcomes of characterization and environmental stability investigations. Preliminary inquiries revealed that the orodispersible formulation was cytobiocompatible, palatable and remained intact under specific storage conditions. Summarily, an edible pyrazinamide containing orodispersible film formulation was optimally designed to potentially improve TB pharmacotherapy in children, particularly the under 5 year olds.
KW - Children
KW - Design of experiments
KW - Edible films
KW - Orodispersible formulation
KW - Pediatric drug delivery
KW - Pyrazinamide
KW - Tuberculosis
UR - http://www.scopus.com/inward/record.url?scp=85089408359&partnerID=8YFLogxK
U2 - 10.3390/ijms21165714
DO - 10.3390/ijms21165714
M3 - Article
C2 - 32784947
AN - SCOPUS:85089408359
SN - 1661-6596
VL - 21
SP - 2
EP - 27
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 16
M1 - 5714
ER -