Current Issue : July-September Volume : 2026 Issue Number : 3 Articles : 5 Articles
The poor intestinal permeability of sodium alendronate (NaALD), a BCS Class III drug, severely limits its oral bioavailability. The self-double-emulsifying drug delivery system (SDEDDS) formulation containing phosphatidylcholine (PLG 1.1) demonstrated its ability to form micro- and nano-emulsions under gastric and intestinal conditions, as well as superior permeation across a biomimetic membrane in vitro, achieving 88% drug transfer. The self-emulsification time of both formulations was consistent with the average gastric transit time. In a rat model, the PLG 1.1 system significantly enhanced bioavailability, resulting in a 1.8-fold increase in cumulative urinary excretion of NaALD over 48 hours compared to a reference. In contrast, the other formulation, which did not contain phosphatidylcholine (Smix1 3.0), showed no improvement. It was concluded that the phosphatidylcholine-based SDEDDS represents a viable strategy to overcome the permeability barrier and improve the oral absorption of alendronate....
Background/Objectives: 3D printing, particularly fused deposition modeling (FDM), is an emerging technology in pharmaceutical manufacturing, enabling the customization of dose or release rate to individual patient needs. However, finding the appropriate loading method to ensure the stability of the drug and achieve the targeted dose may be challenging. Furthermore, the drug utilization of most loading methods is poor, which results in considerable waste production and increased environmental burden. This study aimed to compare two post-printing drug-loading techniques: electronic syringe deposition and pan coating on FDM-printed polylactic acid (PLA) tablets. PLA is a biodegradable and biocompatible polymer that is widely used in this field due to its mechanical strength and regulatory approval. Methods: Tablets with honeycomb-shaped infill (30% and 60% infill densities) were fabricated using PLA filaments, followed by loading with a 15% paracetamol solution via either electronic syringe deposition or pan coating. The resulting tablets were assessed for drug content, weight variation, friability%, surface morphology (SEM), drug distribution (Raman mapping), solid-state characteristics (DSC and FTIR), and dissolution performance. Results: The results indicated that pan coating and electronic syringe deposition offered drug utilization up to 88% and 91.7%, respectively, which is superior to conventional soaking methods. Nevertheless, there is a significant difference in drug loading and release rate: pan coating yielded up to 10.14% drug loads and fast release (over 80% in 30 min), while electronic syringe deposition showed lower drug loading up to 4.8% and slower release (less than 80% within 60 min), which could be associated with better mechanical film integrity and higher precision. Both methods met USP standards with a weight loss of less than 1% and maintained the drug’s crystalline state and compatibility with PLA. Conclusions: FDM combined with controlled postprinting drug loading presents a rapid, cost-effective, and flexible novel approach for manufacturing personalized immediate-release tablets, with pan coating potentially being more suitable for commercial scalability and electronic syringe offering precise dosing for personalized therapies....
Background: Bedside manipulation of adult anti-tuberculosis tablets for paediatric dosing is common in low-resource settings, yet it can compromise drug stability. This study investigated how grinding and multi-drug co-suspension affect the supramolecular organisation, thermal stability, and dissolution of isoniazid (INH). Methods: INH raw, INH branded tablets (whole and ground), and multi-drug combination mixtures (MCMs) that simulate paediatric multi-drug-resistant tuberculosis (MDR-TB) regimens were assessed. Samples were analysed as solids and aqueous suspensions using hot-stage microscopy (HSM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Raman spectroscopy, FTIR-ATR, USP dissolution, and HPLC (LOD 0.0015 mg mL−1; LOQ 0.005 mg mL−1). Results: Grinding and co-mixing lowered melting points and masked typical INH events. Spectroscopy revealed the broadening and shifting of OH/NH and pyridinering bands, consistent with the formation of new hydrogen-bonding networks, correlative with supramolecular rearrangements. In multi-drug suspensions, INH fell below the HPLC quantification limit in both pH 1.2 and 6.8 media, despite visible residue, suggesting the formation of non-dissociable supramolecular complexes. Using a validated HPLC assay, no quantifiable INH was detected from the crushed multi-drug suspensions in either pH 1.2 or pH 6.8, whereas intact API/tablets showed measurable release. Conclusions: Cosuspension of INH with companion tuberculosis (TB) drugs disrupts its supramolecular integrity, leading to pre-administration degradation and a loss of quantifiable drug. Dissolution testing showed minimal INH release at pH 1.2 and none at pH 6.8, contrasting with intact tablets/API. These observations highlight that converting an immediate-release tablet into an aqueous suspension fundamentally alters its physicochemical environment and requires rational formulation design to preserve molecular stability, differentiating true resistance from formulation failure....
The development of distinct biopredictive methods for fasted and fed states using a physiologically based biopharmaceutics modeling (PBBM) approach is essential for accurately evaluating drug release from solid oral dosage forms, especially extended-release products. However, a fed state biopredictive method for desvenlafaxine tablets is not currently available. Hence, the study aimed to investigate the application of the USP 3 apparatus to develop biopredictive methods for desvenlafaxine tablets. Initially, an existing fasted state biopredictive USP 2 dissolution method was adapted to increase dissolution hydrodynamics by scaling the rotation speed to 75 and 100 rotations per minute (rpm). Subsequently, two dissolution methods were developed using the USP 3 apparatus to emulate fasted and fed conditions. The fed biopredictability of the methods was assessed using a previously developed GastroPlus model to simulate fed conditions under 800 kcal and 50% fat meal. Statistical analysis of dissolution profiles obtained in the paddle apparatus revealed no significant difference from the original 50 rpm method and lacked biopredictive for the fed state, indicating the unfeasibility of developing such a method in this apparatus. In contrast, USP 3 proved to be an important tool to develop a fed state method, since it was biopredictable based on simulation analysis. Additionally, no significant differences were observed between USP 3 methods employing pH-gradient media and those using 0.9% NaCl as the sole medium. These findings highlight a hydrodynamic-driven approach for applying USP 3 to develop distinct biopredictive dissolution methods for fasted and fed states, particularly for high-solubility drugs formulated in robust hypromellose matrices....
Poor aqueous solubility remains a major limitation for the oral bioavailability of molecules such as felodipine (FDP), necessitating formulation strategies that enhance drug dissolution while remaining compatible with scalable, solvent-free processing. In this study, solid dispersions (SDs) of FDP were prepared using an organic solvent-free supercritical carbon dioxide (scCO2) process with four grades of polyethylene glycol (PEG 4K, 6K, 10K, and 20K) at drug loadings of 10, 20, and 30% w/w. The influence of PEG molecular weight, drug loading, and scCO2 processing conditions on the solid-state properties and dissolution behavior of FDP was investigated. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) revealed a substantial reduction in FDP crystallinity, indicative of partial or extensive amorphization, dependent on polymer grade and processing temperature. All SDs showed markedly enhanced dissolution compared with crystalline FDP and corresponding physical mixtures, with PEG 4K SDs processed at 45 °C and PEG 20K SDs processed at 60 °C exhibiting the most pronounced improvements. Optimized SDs were subsequently incorporated into orally disintegrating tablets (ODTs), which retained the enhanced dissolution performance of the parent SDs, demonstrating that tabletting did not compromise drug release. While both PEG 4K- and PEG 20Kbased ODTs showed rapid dissolution, PEG 20K formulations exhibited superior mechanical integrity, identifying 30% w/w drugloaded PEG 20K SDs as the most suitable system for ODT development. Overall, this study demonstrates a green, solvent-free scCO2-based strategy for producing high-performance solid dispersions and their successful translation into ODTs for poorly watersoluble drugs....
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