Formulation of Dosage Forms with Proton Pump Inhibitors: State of the Art, Challenges and Future Perspectives

Abstract

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.

Compounding of Liquid and Solid Dose Adjustable Formulations with Pantoprazole: Comparison of Stability, Applicability and Suitability

“…The third formulation (F3) contained the commercially available vehicle SyrSpend Alka ® (Fagron, the Netherlands). Pantoprazole, like many other PPIs, requires an alkaline ingredient with sufficient acid-neutralizing capacity to facilitate the drug’s safe passage through the stomach [ 4 , 5 ]; hence, 8.4% sodium bicarbonate solution was added. Previously, it was published that pantoprazole oral liquid formulation prepared extemporaneously from registered tablets in 8.4% sodium bicarbonate solution was stable in amber polyethylene terephthalate bottles for 62 days at 2–8 °C [ 39 ].…”

“…All samples after mixing with methanol were filtered through a 0.45 µm membrane filter (Agilent Technology, SAD). Degradation rate in an acidic environment (forced degradation) is expected to follow exponential decline (first-order kinetics) [ 4 ] according to Equation (2): where: A —concentration at time t [µg/mL], A 0 —theoretical concentration at time 0, k —constant of degradation and t —time.…”

“…Thus, PPIs must be protected against premature activation in the stomach by adequate formulation, such as enterocoated tablets, pellets and capsules. They are relatively stable at pH = 7.0, but decompose in acidic solutions, and gastroresistant coating provides side site-specific release in the small intestine [ 1 , 2 , 3 , 4 , 5 ].…”

Microspheress Types Preparation Evaluation and Applications: A Review

“…The volume and subsequently the density of microsphere carrier are calculated from two pressure readings. [28] C. Electron-Spectroscopy [Esca -Analysis] Electron spectroscopy for chemical analysis (ESCA) is a method to determine the surface chemistry of microspheres. This method provides a mean for the surface's atomic composition determination.…”

Gram-Scale Synthesis of Sulfoxides via Oxygen Enabled by Fe(NO3)3·9H2O

“…Blockbuster drugs such as Omeprazole, Modafinil, and Sulindac are featured with sulfoxide groups in Scheme a. Omeprazole, treating gastrosia via Smiles rearrangement in vivo reducing the acidity of the stomach, reached global sales of $17 billion in 2007. Modafinil, a specific remedy for narcolepsy, achieved sales of $1.8 billion in 2012.…”