Quality by Design (QbD) Enabled and Central-Composite Design Assisted Approach for Formulation of Oral Herbal Gastro-retentive In-situ Gel

The delivery of herbal medications is currently a growing area in pharmacy. One of the areas of interest for the scientists conducting pharmaceutical research is the use of floating drug delivery system (FDDS) for herbal medicine. In this study, we developed an oral herbal gastro-retentive in-situ gel using extracts from Azadirachta indica and Piper longum Linn, employing the quality by design (QbD) approach.

For the formulation and optimization of an oral herbal in-situ gel, a central composite design (CCD) was used. This design is based on 2-level factorial designs that have been supplemented with center and axial points to match quadratic models. The amounts of two independent variables, gellan gum (X1) and calcium carbonate (X2), were altered at five distinct levels. For the current investigation, the response variables viscosity (Y1), floating lag time (Y2), and gelling time (Y3) were used. According to DoE software, a total of 13 formulations were prepared by changing the gellan gum and calcium carbonate concentrations.

The optimized formulation (OF2), which contains gellan gum 0.293% & calcium carbonate 0.706, satisfies the requirements of quality target product profile (QTPP) and critical quality attributes (CQA) for oral herbal in-situ gel with 75% and 73% drug content. OF2 had a 35.5 s gelling time, a 53 s floating lag time, and a viscosity of 53 cps. The formulated oral herbal in-situ gel exhibited stability for over 2 months under both freezing (-4 °C) and 40 °C with 60% relative humidity (RH) storage conditions.

The developed formulation presents a promising and innovative approach to enhance the gastric retention of herbal extracts, ultimately amplifying their therapeutic efficacy. This paper establishes the foundation for future preclinical and clinical studies on an oral herbal in-situ gel containing long pepper and neem leaf extracts for the treatment of peptic ulcer disease (PUD).