Aqueous-Based Cellulose Acetate Butyrate Dispersion: Screening of Process and Formulation Variables to Obtain Verapamil HCl-Controlled Release Beads

摘要

The objectives of the present investigation were to evaluate the possibility of using a custom-designed cellulose acetate butyrate(CAB) pseudolatex dispersion on Verapamil HCl-loaded beads for sustained release of the drug. Excipient compatibility was studied by thermal analysis. X-ray diffraction, and content analysis. Inert beads (Nupareil) were loaded with verpamil HCl and subsequently coated with CAB pseudolatex dispersion. Process and formulation factors were screened by PlackettBurman screening design in order to idenfity the most important factors affecting the amount of verapamil HCl released in 12 hours. X-ray diffraction pattern and content analysis showed no degradation of verapamil HCl and suggested absence content analysis showed no degradation of verapamil HCl and suggest absence of any interaction. Howeverk thermal analysis indicated an interaction between verapamil HCl and excipient. A polynomial equation was developed to show the relationship between depenent and independent variables. The mathematical model fitted the data and explained 98.05% of variability in the response. The difference between observed and predicated values of an given run did not exceed 6% of maximum cumulative release at 12 hours. Plackett-Bureening designi idnetified coating weight gain, duration of curing , and amount of plasticizer as the most important factors determining cumulative percent released in 12 hours. Amount of Polydextrose /HPMC(Opadry II), spray rate, fluid bed coater outlet temperature ,and atomizing pressure had no statistically significant (p<0.05) influnce on the response.