Intelligent industry-oriented oro-solid formulation of famotidine: Advanced statistical optimization and Ex-Vivo characterization

• The intelligent industry-oriented oro-solid formulation was developed to overcome the limitation of liquid in-situ system. • Taguchi design was accomplished to recognise the CMAs and CPPs. Box-Behnken design was explored to correlate the screened variables and identified CQAs. • Developed intelligent formulation has instant gelling time, high mucoadhesion time, and strength, as well as better control of release. • The developed formulation can be helpful in the industry, increases patient compliance, processing and stability. Sol-Gel is the conventional approach for in-situ formulation having several limitations, including instability, stringent storage conditions, dose inaccuracy, inconsistent drug release, and patient inconvenience. The aim of the present investigation was to design and characterize an intelligent oro-solid in-situ targeted dosage form of Famotidine (FTD) incorporating the cross-linked chitosan-vanillin (CrL-CSV) which instantly converted into a gel upon contact with acidic media. CrL-CSV was designed using microwave-assisted method inculcating FTD and vanillin (VNL). Interaction was observed using FTIR and DSC. QbD was applied to develop intelligent formulation. Taguchi design was accomplished to screen significant critical material attributes (CMAs) and process parameters (CPPs). Box-Behnken design (BBD) was used to correlate the CMAs/CPPs: the amount of CS, VNL, microwave time, and critical quality attributes (CQAs): % FTD release, mucoadhesive strength, and viscosity. CrL-CSV were evaluated using various in-vitro , ex-vivo characterization and stability. FTIR and DSC revealed no interaction between the FTD and excipients. The amount of CS, VNL, and microwave time were screened as significant variables due to the high S/N ratio and delta value from the Taguchi design. A significant effect of CMA/CPP on the CQAs was observed in BBD. The optimum CrL-CSV was designed accomplishing 8.74 % chitosan (CS), 0.94 % VNL exposing 80sec in microwave. Immediate gelling (<1min.), desired viscosity (51432.6cps), optimal mucoadhesion strength (0.40 N), better control on drug release (91.5 % in 8 h) and high stability were achieved in the optimum batch of CrL-CSV. An intelligent formulation inculcating the CrL-CSV was developed, which has instant gelling time, high mucoadhesion time, and strength, and controlled release with desired physical properties. Progressive tools like Taguchi and BBD was explored. The formulation can be helpful at industry as it increases patient compliance, processing and stability.