The rate and extent of drug dissolution in the gastrointestinal (GI) tract are highly dependent upon drug physicochemical properties and GI fluid properties. Biorelevant dissolution media (BDM), which aim to facilitate in vitro prediction of in vivo dissolution performance, have evolved with our understanding of GI physiology. However, BDM with a variety of properties and compositions are available, making the choice of dissolution medium challenging. In this tutorial, we describe a simple and quantitative methodology for selecting practical, yet physiologically relevant BDM representative of fasted humans for evaluating dissolution of immediate release formulations. Specifically, this methodology describes selection of pH, buffer species, and concentration and evaluates the importance of including bile salts and phospholipids in the BDM based upon drug substance log D, pKa, and intrinsic solubility. The methodology is based upon a mechanistic understanding of how three main factors affect dissolution, including (1) drug ionization at gastrointestinal pH, (2) alteration of surface pH by charged drug species, and (3) drug solubilization in mixed lipidic aggregates comprising bile salts and phospholipids. Assessment of this methodology through testing and comparison with literature reports showed that the recommendations correctly identified when a biorelevant buffer capacity or the addition of bile salts and phospholipids to the medium would appreciably change the drug dissolution profile. This methodology can enable informed decisions about when a time, complexity, and/or cost-saving buffer is expected to lead to physiologically meaningful in vitro dissolution testing, versus when a more complex buffer would be required.
Background
Three-dimensional printing (3DP) is an emerging technology used to describe 3D products manufactured on a digital design platform and in a layer by layer fashion. 3D printing technology has appeared as a major technological revolution of the recent years leading to the manufacturing and production of novel medical products and devices in pharmaceutical industry. The new technology has gained considerable attraction when the first commercial 3D tablet Spiratam® (levetiracetam) was approved by FDA in August 2015.
Main text
The key aspect of printing technology in the field of drug delivery is its versatility to create potential novel oral dosage forms. It also enables rapid, safe, and low-cost development in the production process which consequently leads to wide applications of this new technology in pharmaceutical fields. 3D printing also enhances patient convenience to further improve the medication compliance.
Among various technical trends for fabricating 3D objects, extrusion-based printing, powder-based binding, and inject printing methods are of particular interest to the pharmaceutical industry which are discussed briefly in this paper. This study also provides different applications of 3D printing technology and highlights the impact of 3D printing as an innovative promising technology through presenting some examples as experimental studies in the fabrication of oral drug delivery systems.
Conclusions
Through reviewing some experimental studies, this mini review has shown that 3D printing technique can be successfully used on a small scale to produce tailored doses of drug products and has great advantages experimentally in the production of oral doses forms. Concerning the future of 3D printing, the new technology is likely to focus on production in hospitals and pharmacies for individuals or niche groups with specific needs.
3D printing may also offer an attractive new research and development opportunity to improve drug formulation and administration of existing active pharmaceutical ingredients.
Graphical abstract
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