Study On The Formulation Of E-S Double Layer Tablet

In this paper, we studied the prescription and preparation process of E-S double-layer tablets, and verified the preparation technics.In the study of preformulation, we investigated the physical and chemical properties of the active pharmaceutical ingredients(APIs) of E and S firstly, and then researched the compatibility of the excipients and the APIs.According to the clinical data, the clinical recommended dose of E is 10 mg/d, the reglular dose of S is 20 mg/d. Thus, the E-S double-layer tablet strength was 10 mg/ 20 mg(E / S) and the tablet weight was designed to be 200 mg, with E layer and S layer having the same weight of 100 mg.On the basis of preformulation studies, we screened and optimized the prescription of E layer and S layer. E and S belong to the BCS II classification drugs, which are of low aqueous solubility and high permeability. The absorption degree of E and S is mainly determined by the dissolution rate. E is a hydrophobic drug with the solubility of about 0.01 mg/mL. E raw material was micronized and solubilizing agent was used to improve the dissolution. The excipients chosen should be permitted to be used in oral tables and are compatible with the APIs. Using single factor expriments, we screend the excipients with dissoluion profile as the evaluation criteria. In the screening of E layer’s prescription, we obtained the suitable amounts of disintegrant, solubbilizer, bonding agent, and conformed the prescription. S is practically insoluble in water, and has poor chemical stability. We should pay more attention on the excipients for which would have great effects on the dissolution rate and the degrated substances. Additionally, S is prone to be oxidated, so we added antioxidants in S layer to ensure the stability during the preparation process and storage period. We studied the effect of S particle size and the relevantexcipients on the dissolution rate using single factor designe experiments to determine the appropriate parameter and excipients. And then the excipients amounts were optimized.According to the optimized prescription and technics, we producted three batches of E-S bilayer tablets(Lot: 20140701, 20140702, 20140703) to validate the preparation process. Results showed that the preparation process is stable and reliable. Comparing to the E brand-name drug and S brand-name drug,the produced E-S double-layer tablets(Lot: 20140701)have the similar dissolution profiles of E and S in four different dissolution media. The similarity index of the dissolution profiles are all above 50.