| Mexican Tea Herb (MTH) belongs to the Chenopodiacea family, which is the main active component of commercial capsule Jinghuaweikang. And it can kill Helicobacter pylori (Hp) and treat gastric ulcer. In vitro, H. pylori are highly sensitive to MTH, of which the minimal inhibitory concentrations for strains (MIC, mg/mL) is0.039-0.078, which is lower than antibiotics in clinic. However, the commercial formulation is conventional oral soft capsule, which has no good effective treatment in clinical practice. It may be that the oral absorption of MTH is very low and the dosage form has no targeted therapy. Thus it is a logical way to improve the therapeutic efficacy of MTH. The objection of present work was to develop a Intragastric Floating Tablet that localizes the antibiotics at the site of infection to achieve bactericidal concentrations and will ensure effective localized treatment for the pathogen. It can improve the therapeutic efficacy of MTH by increasing the gastric residence time and reduce the dosing frequency by prolonging the drug release time.Because MTH is the liquid feedstock drug, we use silicon dioxide to absorb MTH. And the optimal excipients were obtained by orthogonal experimental design. Its content was determinated by HPLC.MTH floating tablets were prepared by direct powder compression, which is taken orally twice one day, using HPMC K15M and PEO WSRN-750as matrix, Calcium carbonate and Glyceryl behenate as the floating agent, Croscarmellose sodium as expansion agent, And Microcrystalline cellulose "Avicel PH102" as filler. Based on prescription single factor studies, the formulation was optimized using central composite design-response surface methodology. Independent variables were the weight ratio of HPMC K15M and PEO WSRN-750(X1), the ratio of Ac-Di-Sol and CaCO3in adjuvant(X2,X3), while response variables were time of80%dissolution content, floating lag time and total floating duration. The optimized formulation was as follows:X1=2.13; X2=5%; X3=10%.The in vitro dissolution study was performed by using basket apparatus, at a rotational speed of100rpm. Exactly900mL of0.1N HCl with SDS (2.0%w/w) was used as the dissolution medium and was maintained at37±0.5℃. The drug release data of selected formulation were fitted into different model:the zero-order, first-order, and Higuchi’s square root of time. For the selected formulation, the best fit with highest R2coefficient was shown by zero-order (R2=0.9673), followed by Higuchi-model (R2=0.9629). To confirm the exact mechanism of drug release, the dissolution data were fitted according to Korsemeyer-Peppass law equation. And the n values of formulation were0.7169,0.45<n<0.89, which suggested that the release of MTH from the tablet followed non-Fickian kinetics.To increase the long-term storage stability of MTH intragastric floating tablets, they were coated using materials Eudragit RS30D/RL30D (m/m=1:1). And the accelerated stability test of coated MTH floating tablets was examined at the condition of RH65%,30℃for6months. The results showed that the tablets had no significant changes in appearance and floating behaviors. The content of MTH and the drug release were qualified.This study also evaluates the gastric retention ability of MTH floating tablet optimum formulation. In vitro, the floating lag time is6.4min and the total floating time is more than8h. Based on these promising in vitro results, in vivo studies in healthy volunteers were carried by y-scintigraphy. Gamma scintigraphic images demonstrate that the gastric floating tablet is retained in stomach for5.80±0.50h after the administration, while the reference tablet is1.35±0.45h, indicating that gastro retentive time was increased by floating principle. |
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