Real-time quality control of pharmaceutical dosage forms requires rapid, non-destructive analytical technologies that provide chemical specificity while maintaining high throughput. Here, an extended short-wave infrared (eSWIR, 1000-2500 nm) line-scan hyperspectral imaging system (L-EOS 2.5e, Photon Etc.) was evaluated for spatially resolved classification of pharmaceutical tablets. The system was evaluated at integration times of 2, 0.2, and 0.02 ms using Standard Normal Variate normalization, Savitzky-Golay second-derivative preprocessing, and an error-correcting output codes support vector machine classifier. Product-level classification of 11 pharmaceutical products achieved accuracies of 99.99%, 100%, and 97.6% at 2, 0.2, and 0.02 ms, respectively. A more challenging manufacturer-level discrimination task involving three 500 mg acetaminophen products containing the same active pharmaceutical ingredient and labeled dose achieved accuracies of 99.7%, 98.6%, and 89.3% at the corresponding integration times. These results demonstrate the potential of eSWIR hyperspectral imaging for rapid, spatially resolved pharmaceutical product discrimination and high-throughput inspection.

Punch sticking remains one of the most persistent challenges in tablet manufacturing, leading to surface defects, tablet weight variability, reduced productivity, and costly process interruptions. This manufacturing issue continues to increase with the growing molecular complexity of modern active pharmaceutical ingredients (APIs), which are strongly influenced by material characteristics that promote particle-tool interactions. For instance, thermal sensitivity in low-melting compounds promotes softening under frictional heat, hygroscopicity facilitates the formation of adhesive capillary bridges, and high ductility increases the effective contact area, collectively promoting persistent material transfer to the tooling. This review consolidates current understanding of punch sticking, with particular emphasis on the three-force model describing the balance between API-punch adhesion (FAPI-pun), API-API cohesion (FAPI-API), and API-excipient interactions (FAPI-exp). Experimental approaches used to evaluate sticking are reviewed and reorganised into a stage-wise framework comprising powder-based methods, compaction-based methods, powder residual based, and tablet-based techniques. In addition, predictive approaches employed to understand sticking behaviour are systematically summarised, together with their respective advantages and limitations, highlighting the transition toward proactive, data-driven manufacturing strategies. Importantly, key knowledge gaps are identified, including limitations in early-stage prediction, insufficient quantitative mechanistic insight into adhesion and detachment processes, material-specific variability, and the absence of dynamic models' representative of industrial operating conditions. By integrating mechanistic insight with experimental and modelling perspectives, this review establishes a structured framework to guide predictive, material-informed, and industrially relevant control of punch sticking in modern pharmaceutical tabletting.

Background: Oral bisphosphonates are first-line osteoporosis therapy but can cause mucosal chemical injury when tablets are retained rather than swallowed correctly. This risk is heightened in cognitively impaired older adults with dysphagia or difficulty complying with medication administration guidelines. Case Presentation: A 73-year-old female nursing home resident with advanced vascular dementia presented with 24 h of oral pain, reduced intake, lethargy and new facial swelling. She had received monthly ibandronic acid 150 mg for two years, with documented difficulty swallowing tablets but no formal swallowing assessment. Examination showed ulceration of the left lower lip and anterior tongue with mild vestibular swelling. Clinical investigations excluded haematinic deficiency and osteonecrosis; traumatic, lichenoid, vesiculobullous and neoplastic causes were considered unlikely based on distribution, clinical features and temporal association with the recent dose. Bisphosphonate-associated chemical mucosal injury was diagnosed by hospital dental services. Ibandronic acid was discontinued, topical treatment initiated, and ulcers resolved by three weeks. Denosumab was substituted in view of the patient's dysphagia and cognitive status. Discussion: This case supports the existing literature identifying inappropriate administration-often linked to dysphagia or physical impairment-as a leading cause of oral bisphosphonate-associated ulceration, typically affecting the tongue and lower lip. Ibandronate-related cases are rarely reported, likely reflecting prescribing frequency rather than lower risk. Current guidelines lack explicit recommendations addressing dysphagia or cognition in prescribing decisions. Conclusions: Presence of dysphagia and cognitive status should be assessed before and during oral bisphosphonate therapy. New oral pain, ulceration or facial swelling should prompt oral examination and medication review, with alternative antiresorptive agents considered when oral administration is impaired.

This study compares conventional dissolution apparatuses (USP II and IV) with advanced biorelevant models (TIM-2 and the Dynamic Colon Model, DCM) for assessing colonic drug dissolution. Theophylline dissolution from modified-release Uniphyllin Continus® tablets was evaluated across varying hydrodynamic conditions, with the DCM serving as a physiologically validated benchmark. Dissolution was highly dependent on USP II paddle speed (50-200 rpm). In the USP IV increasing flow rate (4-50 mL min[-1]) increased 24 h dissolution but had relatively low impact at 1-5 h. In both systems, the lowest agitation conditions (50 rpm and 4 mL min[-1]) provided the closest agreement to DCM profiles. A simplified TIM-2 configuration was used to isolate hydrodynamic effects, demonstrating motility-dependent release, with slower mixing producing dissolution profiles most similar to the DCM. Incorporation of dewatering improved agreement with the stimulated DCM condition for all systems. The consistent trend across systems of improving similarity to the DCM data with decreasing agitation suggests that conditions below the ranges tested here may be warranted in future studies. USP II and USP IV remain practical and robust tools for quality control but TIM-2 and the DCM better replicate colonic hydrodynamics. TIM-2, even in its simplified configuration in this study, offers additional capability to modulate peristaltic motility patterns and provides a promising platform into which the standard TIM colonic fluids, secretion and absorption functions, can be progressively reintroduced to improve biopredictivity. These findings highlight the complementary role of conventional and advanced dissolution approaches and support integrating physiologically relevant parameters into dissolution testing frameworks to improve biopredictive assessment for modified release formulations.

New ecological, sustainability and practicality analytical methodologies became constant in the modern pharmaceutical analysis. Likewise, a simple, rapid, stability-indicating high-performance liquid chromatography (HPLC) method was developed and validated for simultaneous determination of lamivudine (3TC), zidovudine (ZDV) and nevirapine (NVP) in pharmaceutical formulations. The HPLC method was carried out on a monolithic C18 column (100 mm × 4.6 mm i.d.), maintained at 30°C. The mobile-phase consisted of ammonium acetate (pH 4.5; 10 mM)-methanol-acetonitrile (65:28:7, v/v/v), run at a flow rate of 2.0 mL/min, using photodiode array (PDA) detection at 270 nm. Validation parameters such as the specificity, linearity, precision, accuracy and robustness were evaluated according to the International Council for Harmonisation (ICH) guidelines. From the results obtained, the developed HPLC method was successfully applied for the simultaneous quantitative analysis of 3TC, ZDV and NVP in tablet dosage forms. The chromatographic separation was obtained in less than 3 min and it was suitable for high-throughput analysis. In addition, the greenness assessment, the holistic overall evaluation and the practicality check using the novel Analytical GREEnness Metric Approach and Software (AGREE) calculator, the RGB-12 model and Blue Applicability Grade Index (BAGI), respectively, were performed. The results demonstrated the environmental friendliness (AGREE), practicality (BAGI) and holistic sustainability profile (RGB-12 model) of the proposed method.

Pediatric maintenance therapy for acute lymphoblastic leukemia requires prolonged daily administration of 6-mercaptopurine (6-MP), a drug characterized by a narrow therapeutic index and substantial interindividual variability, creating a need for flexible and patient-friendly dosage forms. This study aimed to develop pediatric chewable tablets 6-MP using hot-melt extrusion and fused deposition modeling (FDM) 3D printing. Preformulation studies and rheological characterization were performed to support formulation development. The influence of internal architecture on porosity, disintegration, mechanical properties, and chewability was investigated by varying infill density. Among the evaluated architectures, 30% infill provided the best balance between structural integrity, porosity, rapid disintegration, and softening after saliva exposure, ensuring adequate chewability. Tablets exhibited accurate drug content (99.5 ± 2.2%). Beyond their immediate-release behavior, complete drug release was achieved within 15 min, while colloidal nanostructures were spontaneously formed, associating approximately 11% of dissolved 6-MP, suggesting a hybrid release mechanism combining rapid drug availability with nano-mediated modulation. Dynamic light scattering and transmission electron microscopy confirmed these findings. Overall, the developed platform demonstrates the potential of FDM-based structural engineering to produce personalized pediatric medicines and reveals that thermally processed polymeric matrices may function as dynamic drug delivery systems rather than conventional immediate-release dosage forms.

This study aimed to enhance the physicochemical properties of curcuminoids by preparing an inclusion complex and formulate an orodispersible tablet (ODT) suitable for elderly patients. A purified curcuminoid was complexed with hydroxypropyl-β-cyclodextrin (HP-β-CD). A design of experiments was employed to optimize the formulation by investigating the effects of a binder and a superdisintegrant on critical tablet attributes. The final optimized ODT was evaluated for compliance with pharmacopeial standards. The 1:1 molar ratio curcuminoid:HP-β-CD complex was identified as optimal, providing a substantial (214-fold) increase in solubility. The complex demonstrated superior photostability, thermal resistance, and ambient storage stability compared to the uncomplexed curcuminoid. The optimized ODT formulation, exhibited excellent mechanical robustness and achieved a rapid disintegration time of 22.21 ± 1.94 s. In vitro dissolution studies showed enhanced drug release, achieving 97.79 ± 0.66% release at 60 min and demonstrating a distinct dissolution profile compared to a commercial non-complexed formulation. This work presented a rational, dual-strategy formulation approach that combines molecular-level solubility enhancement with dosage form optimization to improve the in vitro performance of curcuminoids. The findings highlight the potential of cyclodextrin-based ODT systems as a scalable platform for delivering poorly soluble phytochemicals, particularly for geriatric and dysphagic populations.

GENE-A, a small molecule classified as a BCS Class IV compound, was formulated as a spray dried amorphous solid dispersion (SDD) using HPMC-AS polymer for oral delivery and compressed with additional excipients to yield tablets. Owing to a high clinical daily dose projection, the possibility of administering multiple tablets in applesauce was explored for patient compliance. Since GENE-A crystallized to a hydrate in aqueous media in previously conducted solubility studies, dispersion of SDD tablets in applesauce (aqueous medium) necessitated the development of an analytical method to detect low levels of crystallinity in these mixtures. Using transmission PXRD and multistep sample preparation procedure, a calibration curve was obtained by employing powder blends with matching composition as SDD tablets, spiked with different amounts of crystalline hydrate, dispersed in applesauce. From this curve, the limits of detection and quantitation of crystalline active in these samples were determined to be 1.8 and 4.9% respectively. A 8.5-12% error of prediction for % crystallinity was obtained for validation samples which may be attributed primarily to sample preparation challenges such as retention of water in the centrifuged samples. Using this method, % crystallinity was determined to be < LOD in the test samples, i.e. film coated SDD tablets (for clinical use) dispersed in applesauce at T = 0 and 2 h. Our study is the first to demonstrate the development of a PXRD based method for detecting low levels of crystallinity in a semi-solid matrix to monitor physical stability of an active in drug-vehicle mixtures.