Quantitative effects of formulation process variables on antitumor activities of doxorubicin nanoparticles
Keywords:
Breast Cancer, Doxorubicin, Factorial design and Drug therapy failure.Abstract
Background and objectives: Drug therapy failure is still a recurring clinical phenomenon attributed to a host of factors among which are formulations shortcomings resulting from processing and manufacturing variables leading to different therapeutic effectiveness of pharmaceutical products of the same chemical entity but manufactured by different companies.
This study was aimed at investigating the effects of process variable on therapeutics activities of doxorubicin nanoparticles using a 23 factorial experimental design to study the effects of three independent variables, the production technique (A), the homogenization speed (B) and the drying technique (C) on the therapeutic activity(antitumor) of doxorubicin nanoparticles.
Materials and methods: Eight (8) different formulations, (DX1-8) of doxorubicin nanoparticles were prepared using both single and double emulsion evaporation techniques. The yield and the amount of drug entrapped were mathematically calculated. The release profiles of the formulations were determined using a type II USP dissolution apparatus and a UV spectrophotometer. Estimations of therapeutic effectiveness of the formulations were carried out through cell mortality assay using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) technique.
Results and conclusion: Doxorubicin nanoparticles formulations were successfully prepared with yield ranging from 72.9-90.5% indicating high scale up possibility. The differences in antitumor activities observed were significant (p? 0.05), which may be as a result of marked differences in percentage drug entrapped and drug release profile of the formulations. The factors investigated in this study independently and jointly affected the antitumor activities of the doxorubicin formulations significantly and were ranked, A ? AC ? C ? ABC ? B. This study clearly linked therapeutic effectiveness (cytotoxicity/antitumor) of doxorubicin nanoparticles to the manufacturing variables. There is therefore the need for pharmaceutical manufacturers to optimize their manufacturing processes to prevent drug therapy failure.
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