OBJECTIVE To analyze the formulation composition and process of the reference formulation of Premarin^®, a conjugated estrogens tablets based on the reverse engineering technology, to provide a basis for the development of the generic version of conjugated estrogens tablets.

METHODS Literature research was conducted to obtain the formulation information of conjugated estrogens tablets; scanning electron microscopy-energy dispersive X-ray spectrometry was used to analyze the composition of the tablet core; tablets with comparable tensile strengths to the reference formulation were prepared by wet granulation and powder direct compression, and the process of reference formulation was determined by scanning electron microscopy imaging and macroscopic hydration rate; a batch of tablets was produced in accordance with the determined core formulation information and process to compare the quality and in vitro dissolution behavior of the tablets with the reference formulation. A batch of tablets was produced according to the determined core formulation information and process and compared with the reference formulation in terms of quality and in vitro dissolution behavior.

RESULTS Composition of the reference formulation was as follows: API, calcium phosphate, carnauba wax, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol 400, powdered cellulose, sucrose, titanium dioxide, coloring agent (different specifications of different colors of the tablets). The core of the tablets main ingredients was as follows: API, microcrystalline cellulose, calcium phosphate, lactose, hydroxypropylmethyl cellulose, magnesium stearate. cellulose, magnesium stearate. The reference preparation process may be a powder direct compression process as preliminarily determined by scanning electron microscopy secondary imaging and macroscopic hydration rate. The self-developed preparation prepared based on the reverse engineering results was consistent in quality and had similar in vitro release behavior with the reference formulation.

CONCLUSION Reverse engineering can be used to incorporate the development of conjugated estrogens tablets and prepare tablets of consistent quality with the reference formulation.