EFFECT OF PLURONIC F127 AND TRYPSIN CONCENTRATIONS ON THE IN VITRO RELEASE PROFILE OF NPH

Muhammad Sultan, Nova Southeastern University
Kris Piyarong, Nova Southeastern University
Wael Mahdi, Nova Southeastern University
Young M. Kwon, Nova Southeastern University

Abstract

Objective. This current study focuses on further investigation of the effect of varying the hydrogel and subcutaneous enzymes concentrations on the release profile of insulin from the modulated NPH. Background. Clinical evidence from previous studies has shown that NPH insulin release kinetics is characterized by a pronounced peak within the first few hours after a single subcutaneous injection, and then insulin level declines in less than one day which is insufficient to provide daily basal insulin requirement. In our previous work, NPH insulin-loaded Pluronic F127 (PF-127) hydrogel was prepared and its release was tested in an in vitro model. Also, we have been exploring the effect of subcutaneous enzymes on NPH dissolution. Methods. NPH Insulin crystals were loaded in different concentrations of Pluronic F-127 (PF-127). In vitro release of prepared NPH-hydrogel was conducted in phosphate buffered saline (PBS; with 0.01% Tween 80) at pH 7.4 and 37 °C in dialysis cartridges (MW-cutoff 1000 kDa). Trypsin, as a model subcutaneous enzyme, at different concentrations were added to the release medium during the study. Percent release at 6 hour time points between groups were compared using Student’s t-test and ANOVA. Results. In vitro release profiles of NPH changed significantly in the presence of the gel matrix (PF127), especially during the first several hours, exhibiting relatively constant with reduced initial release. Changing the concentration of Pluronic F127 as well as the enzymes concentration exhibited proportional effects on the release of insulin (p<0.05). Conclusion. Insulin release from NPH crystals in an injectable matrix was affected by the polymer concentrations as well as the presence of enzymes. These findings may further pave ways for overcoming some of the drawbacks in microcrystalsbased basal insulin therapy. Grants. This work was supported by Nova Southeastern University, Health Professions Division (HPD) Research Grant and Saudi Arabia Cultural Mission (SACM).

 
Feb 12th, 12:00 AM

EFFECT OF PLURONIC F127 AND TRYPSIN CONCENTRATIONS ON THE IN VITRO RELEASE PROFILE OF NPH

POSTER PRESENTATIONS

Objective. This current study focuses on further investigation of the effect of varying the hydrogel and subcutaneous enzymes concentrations on the release profile of insulin from the modulated NPH. Background. Clinical evidence from previous studies has shown that NPH insulin release kinetics is characterized by a pronounced peak within the first few hours after a single subcutaneous injection, and then insulin level declines in less than one day which is insufficient to provide daily basal insulin requirement. In our previous work, NPH insulin-loaded Pluronic F127 (PF-127) hydrogel was prepared and its release was tested in an in vitro model. Also, we have been exploring the effect of subcutaneous enzymes on NPH dissolution. Methods. NPH Insulin crystals were loaded in different concentrations of Pluronic F-127 (PF-127). In vitro release of prepared NPH-hydrogel was conducted in phosphate buffered saline (PBS; with 0.01% Tween 80) at pH 7.4 and 37 °C in dialysis cartridges (MW-cutoff 1000 kDa). Trypsin, as a model subcutaneous enzyme, at different concentrations were added to the release medium during the study. Percent release at 6 hour time points between groups were compared using Student’s t-test and ANOVA. Results. In vitro release profiles of NPH changed significantly in the presence of the gel matrix (PF127), especially during the first several hours, exhibiting relatively constant with reduced initial release. Changing the concentration of Pluronic F127 as well as the enzymes concentration exhibited proportional effects on the release of insulin (p<0.05). Conclusion. Insulin release from NPH crystals in an injectable matrix was affected by the polymer concentrations as well as the presence of enzymes. These findings may further pave ways for overcoming some of the drawbacks in microcrystalsbased basal insulin therapy. Grants. This work was supported by Nova Southeastern University, Health Professions Division (HPD) Research Grant and Saudi Arabia Cultural Mission (SACM).