Excipients in Pharmaceutical Additive Manufacturing: A Comprehensive Exploration of Polymeric Material Selection for Enhanced 3D Printing.

This review provides a comprehensive overview of additive manufacturing (AM) or 3D-printing (3DP) applications in the pharmaceutical industry, with a particular focus on the critical role of polymer selection. By providing insights into how material properties influence the 3DP process and the quality of the final product, this review aims to contribute to a better understanding of the interplay between polymers and pharmaceutical 3DP. As 3DP technologies are increasingly integrated into pharmaceutical sciences, this review contributes insights into the nuanced process of polymer selection, serving mainly as a foundational guide for researchers and formulators new to the subject seeking to harness the full potential of pharmaceutical 3DP by understanding the physicochemical properties, roles, and functions of used polymers in 3D-printed dosage forms and medical devices.

Correction: Braga et al. Cyclodextrins in Antiviral Therapeutics and Vaccines. Pharmaceutics 2021, 13, 409.

In the original publication [...].

Cyclodextrins in Antiviral Therapeutics and Vaccines.

The present review describes the various roles of cyclodextrins (CDs) in vaccines against viruses and in antiviral therapeutics. The first section describes the most commonly studied application of cyclodextrins-solubilisation and stabilisation of antiviral drugs; some examples also refer to their beneficial taste-masking activity. The second part of the review describes the role of cyclodextrins in antiviral vaccine development and stabilisation, where they are employed as adjuvants and cryopreserving agents. In addition, cyclodextrin-based polymers as delivery systems for mRNA are currently under development. Lastly, the use of cyclodextrins as pharmaceutical active ingredients for the treatment of viral infections is explored. This new field of application is still taking its first steps. Nevertheless, promising results from the use of cyclodextrins as agents to treat other pathologies are encouraging. We present potential applications of the results reported in the literature and highlight the products that are already available on the market.

Inclusion Compound of Efavirenz and γ-Cyclodextrin: Solid State Studies and Effect on Solubility.

Efavirenz is an antiretroviral drug of widespread use in the management of infections with human immunodeficiency virus type 1 (HIV-1). Efavirenz is also used in paediatrics, but due to its very poor aqueous solubility the liquid formulations available resort to oil-based excipients. In this report we describe the interaction of γ-cyclodextrin with efavirenz in solution and in the solid state. In aqueous solution, the preferential host-guest stoichiometry was determined by the continuous variation method using 1H NMR, which indicated a 3:2 host-to-guest proportion. Following, the solid inclusion compound was prepared at different stoichiometries by co-dissolution and freeze-drying. Solid-state characterisation of the products using FT-IR, 13C{1H} CP-MAS NMR, thermogravimetry, and X-ray powder diffraction has confirmed that the 3:2 stoichiometry is the adequate starting condition to isolate a solid inclusion compound in the pure form. The effect of γ-cyclodextrin on the solubility of efavirenz is studied by the isotherm method.

Competing for water: A new approach to understand disintegrant performance.

The understanding of tablet disintegration is still incomplete as not all involved factors and processes are known or accounted for. E.g., the negative influence of soluble fillers, on disintegration is usually attributed to increased viscosity due to dissolved filler. When the most common filler, lactose, dissolves, the viscosity increases only slightly. The impact of binders has hardly been studied systematically. In this study, water uptake and force development as well as water sorption experiments were performed of tablets containing either a soluble or an insoluble filler, one of four different binders, and one of four different disintegrants. For both fillers, one disintegrant performed distinctly worse than the others. For the insoluble filler, dibasic calcium phosphate (DCP), sodium starch glycolate resulted in the longest disintegration, for the soluble filler, lactose, croscarmellose sodium performed worst. Based on the experimental results, the authors introduce the competition-for-water hypothesis, which takes into consideration the amount of freely available water molecules and hydration kinetics of excipients. Soluble fillers bind a large number of water molecules in hydrate shells and prevent, therefore, proper disintegrant action. Previously inconsistent observations can be approached with this hypothesis and a better understanding of the underlying processes and explanations is possible.

Pediatric drug formulations of sodium benzoate: II. Coated granules with a lipophilic binder.

Sodium benzoate is used as a therapeutic agent in the treatment of some rare disorders that predominantly affect children. In preliminary investigations, liquid and semi-solid formulations of sodium benzoate failed because children refuse the oral uptake due to the bad taste of the drug. Recently developed microcapsules with macrogol as a hydrophilic binder raise concern in high-dose treatment regimens because acceptable daily intake limits are exceeded. A novel microcapsule formulation was developed consisting of a lipophilic core with high sodium benzoate load and a saliva-resistant coating. A new powder quality of saturated triglycerides from plant origin was introduced which complies with the Ph. Eur. monograph 'Hard fat'. Sodium benzoate and the triglyceride were mixed and directly extruded at room temperature. The extrudates were spheronized and coated in a fluidized-bed process. The resulting coated granules are small-sized microcapsules and taste neutrally. They can be mixed with food before administration. As the amount of released sodium benzoate is negligible within the first minutes, children do not recognize the bad taste and accept the medication. Recently, sodium benzoate in this novel formulation has been designated by the European Community as an orphan drug in the treatment of non-ketotic hyperglycinemia.