Since their introduction to pharmacotherapy, proton pump inhibitors (PPIs) have been widely used in the treatment of numerous diseases manifested by excessive secretion of gastric acid. Despite that, there are still unmet needs regarding their availability for patients of all age groups. Their poor stability hinders the development of formulations in which dose can be easily adjusted. The aim of this review is to describe the discovery and development of PPIs, discuss formulation issues, and present the contemporary solutions, possibilities, and challenges in formulation development. The review outlines the physicochemical characteristics of PPIs, connects them with pharmacokinetic and pharmacodynamic properties, and describes the stability of PPIs, including the identification of the most important factors affecting them. Moreover, the possibilities for qualitative and quantitative analysis of PPIs are briefly depicted. This review also characterizes commercial preparations with PPIs available in the US and EU. The major part of the review is focused on the presentation of the state of the art in the development of novel formulations with PPIs covering various approaches employed in this process: nanoparticles, microparticles, minitablets, pellets, bilayer, floating, and mucoadhesive tablets, as well as parenteral, transdermal, and rectal preparations. It also anticipates further possibilities in the development of PPIs dosage forms. It is especially addressed to the researchers developing new formulations containing PPIs, since it covers the most important formulary issues that need to be considered before a decision on the selection of the formula is made. It may help in avoiding unnecessary efforts in this process and choosing the best approach. The review also presents an up-to-date database of publications focused on the pharmaceutical technology of formulations with PPIs.

Background/Objectives: Bisoprolol fumarate (BF) is a cardioselective beta-blocker used to treat pediatric heart failure and certain tachyarrhythmias. Currently, it is administered mainly as extemporaneously prepared suspensions from crushed tablets, which may cause issues with dose accuracy, stability, and palatability. Orodispersible minitablets (MODTs) may facilitate administration and individualized dosing, while prolonged release could potentially reduce peak-to-trough fluctuations and, thus, minimize adverse effects such as hypotension or bradycardia. This proof-of-concept study aimed to develop spray-dried prolonged-release microparticles containing BF, incorporate them into MODTs, and evaluate the effect of compression on drug release. Methods: Microparticles were prepared by spray drying ethanolic solutions of BF and ethylcellulose at 40 °C, 50 °C, and 60 °C. Their characterization included scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis and dissolution studies. Selected microparticles were compressed into 3 mm MODTs, which were evaluated for mechanical properties, disintegration, and BF release. Results: Formulations containing 10% BF and 90% ethylcellulose released from 52.6% to 73% of BF after 2 h, increasing to 84.8–90.0% after 8 h and reaching 96% after 24 h. Solid-state analyses indicated complete amorphization of the drug in these microparticles. The spray-drying temperature affected process efficiency but did not significantly impacted morphology or dissolution behavior. The optimized MODTs disintegrated in less than 30 s and had a tensile strength of up to 2.62 MPa. Importantly, compression increased the initial BF release from 26.4% for the microparticles to 43.9% for the MODTs at 0.5 h, resulting in f₂ values of 45.04–48.46. Despite the higher initial BF release, the moderately prolonged-release profile was maintained in the case of MODTs. Conclusions: These findings demonstrate the feasibility of combining prolonged-release microparticles with orodispersible minitablets as a proof-of-concept for a pediatric drug delivery approach.