Purpose: The contemporary investigation was intended to extend and appraise uniqueness of the tablet in tablet formulation with a perception to proffer a quick and protracted relief in gastritis and allied gastric disorders. Materials and Methods: The possible drug-excipient interaction between Esomeprazole Magnesium and formulation constituents/excipients of core and outer tablet was envisaged to map the batch composition formulas for the core tablets. The core tablets were compressed using 6.5 mm die punch (concave) set and outer tablets (devoiding core tablet) were compressed using 14 mm die punch (concave) set with optimized compression load and speed. Based on performance outcome of core tablet and outer tablet batches, during the assessment of the post compression parameters, three batches for tablet in tablet were purposed and compacted, which were later subjected to in vitro release kinetics. The short-term accelerated stability testing of the varied batches of tablet in tablet formulations was executed to predict the environmental influence over the quality of finalized formulation and to ensure that no alteration has been brought in to the formulation during the course of manufacturing process that could negatively impact its stability. The optimized tablet in tablet formulation was compared with the commercially accessible enteric coated Esomeprazole tablet. The maximum plasma concentration (Cmax, mu g/mL) and the corresponding time (Tmax, hour) for the two treatments in each rabbit were estimated through high-performance liquid chromatography in the plasma concentration data. Results: The post-compression parameters of the core tablets revealed that the CT-26 batch, comprising polyethylene glycol as binder and sodium starch glycolate as disintegrant, was best among rest, of all the batches (CT-1 to CT-27), with crushing strength of 3.57 +/- 0.115 kg/cm2, Friability 0.188 +/- 0.002 (% loss), disintegration time of 52.66 +/- 0.57 s, and % drug content was found to be 100.31 +/- 0.32. The post-compression parameters of outer tablet, reveals that the OT-2 batch, comprising microcrystalline cellulose as disintegrant, was best among rest, out of all batches (OT-1 to OT-9), with crushing strength of 5.55 +/- 0.132 kg/cm2, Friability 0.098 +/- 0.004 (% loss), and disintegration time of 161.33 +/- 0.57 s. The analysis of the entire tablet in tablet (T in T-1 to T in T-3) batches reveals that of the T in T-3 (comprising of CT-26 and OT-2) was the best batch, among rest of all batches (T in T-1 to T in T-3), with mean weight 776.95 +/- 0.394 mg, thickness 6.516 +/- 0.028 mm, crushing strength of 6.10 +/- 0.276 kg/cm2, Friability 0.193 +/- 0.006 (% loss), disintegration time of 189.33 +/- 0.577 s, and % drug content 97.36 +/- 0.07. The in vitro release of Esomeprazole magnesium from varied tablet in tablet formulations were also assessed by integrating drug release statistics into diverse release pharmacokinetics models. The maximized regression values (0.991) for tablet in tablet formulations demonstrated the sensible linearity through Higuchi pharmacokinetic model, signifying the formulations as modified release formulation. The accelerated stability studies have demonstrated the consistent sunset yellow color of the optimized formulation, with smooth surface exclusive of any flaws or cracks. The disintegration time of 195.21 +/- 1.468 s, and % drug content was found to be 96.79 +/- 0.539. The observed mean was evident that the release of esomeprazole from the optimized (T in T-3) formulation was quicker than the conventional commercial formulation with relative bioavailability (FR %) 91.861%. Conclusion: In the present study, the tablet in tablet technology was used to formulate an immediate release formulation, in which Esomeprazole Magnesium; an acid labile drug was kept in core tablet and the outer tablet confining acid neutralizing agents. The constituents of core tablet and outer tablet release simultaneously in the stomach acidic environment. The outer tablet containing acid neutralizing agents counterbalance the gastric environment and thus providing favorable pH environment for the release of esomeprazole in stomach. Both the constituents act in synergy to produce desired pharmacological action. This will provide instantaneous relief with the release of acid neutralizing agents from the outer tablet and proffer prolong relief (with the release of esomeprazole from the core table) from the gastric symptoms due to irreversible binding to cysteine residues of the H+/K +ATPase. The clinical action of each drug component will not alter and exhibited their action in synergy. This will offer better therapeutic efficacy and improve patient compliance.
