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Despite ongoing international efforts, many drugs administered to children must be compounded from dosage forms designed for adults because they remain unavailable in commercial formulations that suit their needs. Even though oral drug compounding is common in pediatrics, the extent of this practice has not been well described in recent years. This cross-sectional and retrospective study was conducted at a Canadian university-affiliated, 484-bed, tertiary care pediatric hospital and its rehabilitation centre on two randomly selected days. A total of 606 hospitalized children with 5465 prescriptions were included. Overall, compounded drugs for enteral administration (CDEA) represented 13% of all prescriptions (enteral and parenteral) and 23% of prescriptions for enteral administration. Of the 390 prescribed drugs, 122 required compounding. CDEA were mostly liquids (n = 478 [67%]) and mainly included drugs of the central nervous (35%), cardiovascular (21%), and gastro-intestinal (12%) systems. Nearly half (N = 298 [49%]) of children had at least one CDEA prescribed in their medical file. Many CDEA are available as commercial products in other jurisdictions. Collaboration is needed between all stakeholders to make these drugs available to Canadian children.

Letrozole (LZ) is an aromatase inhibitor, which inhibits the formation of estrogens from androgens. Nanoemulsion is a liquid emulsion formulation utilized to increase solubility, bioavailability, and drug delivery to cancer cells. This study aims to improve LZ oral delivery through formulating solid nanoemulsion (SNE). Peppermint oil, tween 80, and transcutol P were used as an oil, surfactant, and co-surfactant, respectively. The optimized nanoemulsion (NE-3) was then incorporated into solid polyethylene glycol (PEG) to formulate (SNE). The optimized (NE-3), SNE-2, and the available marketed tablet have been compared. The optimized (NE-3) was selected according to specific parameters of optimum small nano-size 80 nm, PDI of 0.181, the zeta potential of-98.2, high transmittance (99.78%), optimum pH (5.6), a high percent of LZ content (99.03 ± 1.90), the relatively low viscosity of 60.2 mPa.s, and a rapid release of LZ within 30 min. NE-3 was selected to be formulated as SNE. LZ's best release rate was 80% in 5 min with a content homogeneity of 99.85 ± 0.04 for SNE-2. Zero-order kinetics is determined to have the greatest R2 values. Field emission scanning electron microscopy (FE-SEM) detected that SNE-2 was (36.75–96.64 nm) with a spherical form and no adhesion or aggregation. FT-IR showed no significant variations in position and shape of the absorption peaks between the pure drug and optimal formulation diagrams. This novel nanoemulsion technology aids in improving the solubility of poorly water-soluble drugs, particularly the SNE delivery method, which has a higher in-vitro release rate and expiration date of LZ than others.

3D printing offers the advantage of being able to modify dosage form geometry, which can be exploited to modify release characteristics. In this study, we investigated the influence of the surface area to volume ratio (SA/V) to change and predict release profiles of 3D printed dosage forms. Geometries with varying SA/V and dosages were designed and printed, and drug dissolution was investigated. Three drug substances were used: pramipexole, levodopa (both BCS I) and praziquantel (BCS II). Two polymers were chosen as matrix formers: polyvinyl alcohol (water-soluble) and ethylene vinyl acetate (inert). Drug release was characterized using the mean dissolution time (MDT) and established equations that describe complete dissolution curves were applied. Predictions were validated with previously un-printed dosage forms. Based on an identified MDT-SA/V correlation, the MDT can be predicted with a deviation of ≤5 min for a given SA/V. Using correlations of fit parameters and SA/V, RMSEP values of 0.6–2.8% and 1.6–3.4% were obtained for the BCS I formulations and RMSEP values of 1.0–3.8% were obtained for the BCS II formulation, indicating accurate prediction over a wide range of dissolution profiles. With this approach, MDT and release profiles of dosage forms with a given SA/V can be precisely predicted without performing dissolution tests and vice versa, the required SA/V can be predicted for a desired release profile.

Fused deposition modeling (FDM) 3D printing was used to produce 3D printed tablets with the thermo-sensitive model peptidomimetic drug enalapril maleate (EM). Two different formulations were prepared to investigate the degradation of enalapril maleate during the FDM 3D printing process. Soluplus® and Eudragit® E PO were chosen as polymers. After hot-melt extrusion (HME) and FDM 3D printing, both formulations were characterised regarding their solid-state properties using DSC and XRD. The degradation of the drug was analysed by determination of the content in the extrudates and 3D printed tablets, and dissolution was assessed. Various approaches have been attempted to prevent degradation of enalapril maleate, including utilization of a larger nozzle diameter and higher printing speeds to reduce heat exposition. None of these approaches were successful in preventing drug degradation. However, significant differences in the amount of degradation between the two formulations with different polymers could be observed. Thus, the FDM 3D printing process was not feasible without any degradation for the thermo-sensitive drug enalapril maleate. A maximum of 85.55 ± 1.48% enalapril was recovered in Eudragit® E PO tablets printed with a 0.4 mm nozzle at a temperature of 180 °C and with a speed of 30 mm/s.

The development of innovative forms of combination drugs is closely related to the invention of the multilayer tablet press, polymers for pharmaceutical applications, the hot-melt extrusion process, and 3D printing in the pharmaceutical industry. However, combining multiple drugs within the same dosage form can bring many physicochemical and pharmacodynamic interactions. More and more new forms of fixed-dose combinations (FDCs) have been developed due to work to overcome the incompatibility of active substances or to obtain different drug release profiles in the same dosage form. This review provides discussions of the application of various innovation formulation technologies of FDC drugs such as bilayer system, multilayer tablet, active film coating, hot-melt extrusion, and 3D printing, taking into account the characteristics of the key ingredients in the FDC formulation and presenting technological problems and challenges related to the development of combination drugs. Moreover, the article summarizes the range of dosage forms that have been made using these technologies over the past 30 years.

One of the major challenges in the development of effective pharmaceutical formulations for oral administration is the poor solubility of active pharmaceutical ingredients. For this reason, the dissolution process and drug release from solid oral dosage forms, such as tablets, is usually thoroughly studied in order to understand the dissolution behaviour under various conditions and optimize the formulation accordingly. Standard dissolution tests used in the pharmaceutical industry provide information on the amount of drug released over time; however, these do not allow for a detailed analysis of the underlying chemical and physical mechanisms of tablet dissolution. FTIR spectroscopic imaging, by contrast, does offer the ability to study these processes with high spatial and chemical specificity. As such, the method allows us to see the chemical and physical processes which occur inside the tablet as it dissolves. In this review, the power of ATR-FTIR spectroscopic imaging is demonstrated by presenting a number of successful applications of this chemical imaging technique to dissolution and drug release studies for a range of different pharmaceutical formulations and study conditions. Understanding these processes is essential for the development of effective oral dosage forms and optimization of pharmaceutical formulations.

The aim of this review is to present the factors influencing the mechanical properties of 3D-printed oral dosage forms. It also explores how it is possible to use specific excipients and printing parameters to maintain the structural integrity of printed drug products while meeting the needs of patients. Three-dimensional (3D) printing is an emerging manufacturing technology that is gaining acceptance in the pharmaceutical industry to overcome traditional mass production and move toward personalized pharmacotherapy. After continuous research over the last thirty years, 3D printing now offers numerous opportunities to personalize oral dosage forms in terms of size, shape, release profile, or dose modification. However, there is still a long way to go before 3D printing is integrated into clinical practice. 3D printing techniques follow a different process than traditional oral dosage from manufacturing methods. Currently, there are no specific guidelines for the hardness and friability of 3D printed solid oral dosage forms. Therefore, new regulatory frameworks for 3D-printed oral dosage forms should be established to ensure that they meet all appropriate quality standards. The evaluation of mechanical properties of solid dosage forms is an integral part of quality control, as tablets must withstand mechanical stresses during manufacturing processes, transportation, and drug distribution as well as rough handling by the end user. Until now, this has been achieved through extensive pre- and post-processing testing, which is often time-consuming. However, computational methods combined with 3D printing technology can open up a new avenue for the design and construction of 3D tablets, enabling the fabrication of structures with complex microstructures and desired mechanical properties. In this context, the emerging role of computational methods and artificial intelligence techniques is highlighted.

The paucity of evidence-based data on formulation characteristics preferred by the children is known to limit the design of tailored paediatric dosage forms. The European Paediatric Translational Research Infrastructure (EPTRI) commissioned a study to evaluate children’s dosage forms perceived preferences in some European countries and explore the feasibility of using the young persons advisory groups (YPAGs) to involve children in formulation research. An online, age-adapted survey was developed and translated into six languages. The survey link was disseminated across seven European countries: Albania, Italy, the Netherlands, and Dutch-speaking part of Belgium, Romania, Spain, and the United Kingdom. Respondents’ (n = 1172) perceived preferences for oral dosage forms primarily differed based on age, health status, and experience. Conventional dosage forms, i.e., liquid (35%), tablets (19%), and capsules (14%), were the most selected. Liquid was widely selected by children less than 12 years and by those healthy and taking medicines rarely. Monolithic solid forms were mostly chosen by adolescents and by children with a chronic disease taking medicines frequently. There was a clear lack of familiarity with more novel dosage forms (e.g., orodispersible films and granules). Noteworthy, granules were not appreciated, particularly by adolescents (52.8%). To rationalise the creation of paediatric formulations, it is important to involve children as active stakeholders and to apply tools assessing children’s perspectives on medicines to inform acceptable dosage form development from the start.

Previously, we have shown that thin-film freeze-drying can be applied to prepare dry powders of bacteria such as Lactobacillus acidophilus . Herein, we tested the viability of L. acidophilus in thin-film freeze-dried powders (TFF powders) filled in delayed-release vegetarian capsules in a simulated gastric fluid (SGF) consisting of 0.1N hydrochloric acid and sodium chloride. Initially, we determined the water removal rate from frozen thin films on relatively larger scales (i.e., 10–750 g). We then prepared and characterized two TFF powders of L. acidophilus with either sucrose and maltodextrin or sucrose and hydroxypropyl methylcellulose acetate succinate (HPMC-AS), a pH-sensitive polymer, as excipients and evaluated the viability of the bacteria after the TFF powders were filled in delayed-release vegetarian capsules and the capsules were incubated in the SGF for 30 min. On 10–750 g scales and at the settings specified, water removal from frozen thin films was faster than from slow shelf-frozen bulk solids. When the L. acidophilus in sucrose and HPMC-AS TFF powder was filled into a delayed-release capsule that was placed into another delayed-release capsule, the bacterial viability reduction after incubation in the SGF can be minimized to within 1 log in colony forming unit (CFU). However, for the L. acidophilus in sucrose and maltodextrin TFF powder, even in the capsule-in-capsule dosage form, bacterial CFU reduction was > 2 logs. TFF powders of live microorganisms containing an acid-resistant material in capsule-in-capsule delayed-release vegetarian capsules have the potential for oral delivery of those microorganisms.

Material suitability needs to be considered for the 3D printing of solid oral dosage forms (SODFs). This work aims to assess the suitability of a CO2 laser (λ = 10.6 μm) for selective laser sintering of SODFs containing copovidone and paracetamol. First, physicochemical characterization of powders (two grades of copovidone, two grades of paracetamol and their mixtures at various proportions) was conducted: particle size distribution, morphology, infrared absorbance, flowability, and compactness. Then, printing was launched, and printability of the powders was linked to their physicochemical characteristics. The properties of the sintered SODFs were evaluated (solid state, general aspect, porosity, hardness, drug content and release). Hence, it was found that as copovidone absorbs at the laser’s wavelength, sintering was feasible without using an absorbance enhancer. Also, flowability, which mainly depends on the particle size, represents the first control line for “sinterability” as a fair flow is at least required. Low compactness of copovidone and mixtures reduces the mechanical properties of the SODFs but also increases porosity, which can modulate drug release. Moreover, the drug did not undergo degradation and demonstrated a plasticizer effect by lowering the heating temperature. In conclusion, this work proves the applicability of CO2 laser SLS printer to produce SODFs.