In Vitro and In Vivo Evaluation of Dark Chocolate as Age-appropriate Oral Matrix.

Swallowing difficulties encountered by geriatric patients who undergo polypharmacy represent a significant challenge that hampers patient compliance and therapeutic management. As an appealing and sensory-pleasing, chocolate-based formulations have emerged as a potential alternative oral dosage form suitable for both the elderly and paediatric populations. However, the extent to which the incorporation of drugs into a chocolate matrix affects their oral availability remains unclear. Therefore, the objective of this investigation was to explore the in vitro and in vivo performance of an ibuprofen-based chocolate dosage form. A matrix based on dark chocolate and the model drug was prepared at two distinct temperatures: 50 and 80 °C. In vitro release studies revealed that ibuprofen formulated through co-melting at 80 °C exhibited a statistically significant slower drug release (p < 0.05) compared to formulations prepared at 50 °C in both FaSSGF (fasted-state simulated gastric fluid) and lipolysis media. The enzymatic degradation of chocolate in the presence of lipase accelerated in vitro ibuprofen release from chocolate matrices. To delve deeper into the bioavailability of ibuprofen within the chocolate formulations, we conducted an in vivo assessment, comparing the pharmacokinetic profiles of ibuprofen in its conventional suspension form with our chocolate-based dosage forms. A notable drop (p < 0.05) in the maximum serum concentration of ibuprofen when incorporated into co-melted or solid-suspension chocolate matrices. However, no significant differences in plasma exposure were observed between the two formulations. These findings shed a light on the potential of chocolate to extend of ibuprofen when integrated into various chocolate matrices, showcasing the potential held by these innovative formulations.

Embedded 3D Printing of Novel Bespoke Soft Dosage Form Concept for Pediatrics.

Embedded three-dimensional printing (e-3DP) is an emerging method for additive manufacturing where semi-solid materials are extruded within a solidifying liquid matrix. Here, we present the first example of employing e-3DP in the pharmaceutical field and demonstrate the fabrication of bespoke chewable dosage forms with dual drug loading for potential use in pediatrics. LegoTM-like chewable bricks made of edible soft material (gelatin-based matrix) were produced by directly extruding novel printing patterns of model drug ink (embedded phase) into a liquid gelatin-based matrix (embedding phase) at an elevated temperature (70 °C) to then solidify at room temperature. Dose titration of the two model drugs (paracetamol and ibuprofen) was possible by using specially designed printing patterns of the embedded phase to produce varying doses. A linearity [R2 = 0.9804 (paracetamol) and 0.9976 (ibuprofen)] was achieved between percentage of completion of printing patterns and achieved doses using a multi-step method. The impact of embedded phase rheological behavior, the printing speed and the needle size of the embedded phase were examined. Owning to their appearance, modular nature, ease of personalizing dose and geometry, and tailoring and potential inclusion of various materials, this new dosage form concept holds a substantial promise for novel dosage forms in pediatrics.

A study of the effects of sodium halides on the performance of air-jet and vibrating-mesh nebulizers.

The influence of sodium halide electrolytes on aerosols generated from the Aeroneb Pro vibrating mesh nebulizer and the Sidestream air-jet nebulizer has been evaluated. Fluids with a range of concentrations of Na halides (i.e. NaF, NaCl, NaBr and NaI) were used as nebulizer solutions and their effect on aerosol properties such as total aerosol output, fine particle fraction (FPF), volume median diameter (VMD) and predicted regional airway deposition were investigated. For both nebulizers, the inclusion of electrolyte significantly enhanced the aerosol properties compared with HPLC grade (deionized) water. Aerosol output, FPF and aerosol fraction less than 2.15 µm were directly proportional to electrolyte concentration. Furthermore, the proportion of aerosols that are likely to deposit in the oropharyngeal region, and the VMD of the droplets were inversely related to the electrolyte concentration for both nebulizers. In general, the inclusion of electrolytes had a greater impact on the aerosol properties of the vibrating-mesh nebulizer. In the Aeroneb Pro, NaI 2.0% (w/v) was the optimum solution as it generated the highest aerosol output, FPF and output fraction below 2.15 µm with the lowest VMD and minimal predicted oropharyngeal deposition. This was attributed to the polarizing ability of iodide ions present in the largest quantity at the air-water interface. This study has shown that the Aeroneb Pro vibrating-mesh device demonstrated greatly enhanced aerosol properties when halides were included in the nebulizer solutions.

Physiological bicarbonate buffers: stabilisation and use as dissolution media for modified release systems.

Bicarbonate media are reflective of the ionic composition and buffer capacity of small intestinal luminal fluids. Here we investigate methods to stabilise bicarbonate buffers which can be readily applied to USP-II dissolution apparatus. The in vitro drug release behaviour of three enteric coated mesalazine (mesalamine) products is investigated. Asacol 400 mg and Asacol 800 mg (Asacol HD) and the new generation, high dose (1200 mg) delayed and sustained release formulation, Mezavant (Lialda), are compared in pH 7.4 Krebs bicarbonate and phosphate buffers. Bicarbonate stabilisation was achieved by: continuous sparging of the medium with 5% CO(2)(g), application of a layer of liquid paraffin above the medium, or a specially designed in-house seal device that prevents CO(2)(g) loss. Each of the products displayed a delayed onset of drug release in physiological bicarbonate media compared to phosphate buffer. Moreover, Mezavant displayed a zero-order, sustained release profile in phosphate buffer; in bicarbonate media, however, this slow drug release was no longer apparent and a profile similar to that of Asacol 400 mg was observed. These similar release patterns of Asacol 400 mg and Mezavant displayed in bicarbonate media are in agreement with their pharmacokinetic profiles in humans. Bicarbonate media provide a better prediction of the in vivo behaviour of the mesalazine preparations investigated.