Journal of Pharmaceutical Innovation最新文献

Purpose

Loratadine, a Biopharmaceutics Classification System (BCS) Class II antihistamine, exhibits dissolution-limited oral delivery due to poor aqueous solubility. This study aimed to develop a hybrid orodispersible tablet (ODT) platform by incorporating a loratadine nanosuspension into a freeze-dried porous matrix to enhance early in vitro dissolution performance.

Methods

A loratadine nanosuspension was prepared using a modified solvent–antisolvent precipitation method combined with high-shear homogenization and characterized for particle size distribution and zeta potential. Conventional ODTs containing raw loratadine and Nano-ODTs incorporating the nanosuspension were prepared using the same mannitol-based freeze-dried matrix. The formulations were evaluated by FTIR, DSC, SEM, disintegration testing, and in vitro dissolution studies.

Results

The pre-lyophilization nanosuspension showed a Z-average diameter of 148.3 nm, PDI of 0.609, and zeta potential of − 26.5 mV. FTIR and DSC analyses indicated compatibility of formulation components and differences in thermal behavior among the formulations. The Nano-ODT exhibited rapid disintegration and higher early loratadine release compared with the conventional ODT under the selected dissolution conditions.

Conclusion

The developed hybrid Nano-ODT platform successfully combined nanosuspension technology with a freeze-dried porous matrix, resulting in improved early in vitro dissolution performance compared with the conventional ODT. These findings support the potential of this approach for improving dissolution-limited delivery of poorly soluble drugs.

Purpose

Monitoring of complex bioprocesses is critical for ensuring product quality in biopharmaceutical manufacturing. This study systematically evaluates the potential of benchtop ¹H NMR (80 MHz) combined with machine learning as a robust process analytical technology (PAT) tool for bioprocess monitoring.

Methods

A total of 128 samples from eight industrial-scale (1,500 L) CHO-K1 cell culture batches producing Trastuzumab biosimilar were analyzed to acquire both 80 MHz and 600 MHz ¹H NMR spectra. Six batches served as training set and two batches as test set. Lasso, Ridge, PLS, and LightGBM models were built with 5-fold cross-validation to predict 36 metabolites, six metal ions, viable cell density (VCD), viability, and antibody titer.

Results

Lasso and PLS models achieved excellent predictions for 36 metabolites (R² > 0.90, RPD > 3.3) using 80 MHz NMR, comparable to 600 MHz results. Furthermore, our framework enabled the indirect monitoring of indicators that are not directly detectable by ¹H NMR under our experimental conditions, including antibody titer, VCD, and metal ions, by leveraging biological correlations. Notably, the 80 MHz Lasso model outperformed its 600 MHz counterpart in predicting antibody titers on the test set (R² = 0.959), benefiting from reduced data complexity in small-sample modeling. Feature importance analysis revealed that the Lasso models captured chemically meaningful signals aligning with standard metabolite peak positions.

Conclusion

Benchtop NMR coupled with Lasso regression provides a low-cost, information-rich, and interpretable at-line monitoring tool for industrial CHO cell cultures. This approach is particularly advantageous for small-sample scenarios and supports multi-parameter process fingerprinting in biopharmaceutical manufacturing.

Background

Glaucoma is recognized as the leading cause of irreversible blindness worldwide, primarily due to the excessive rise of intraocular pressure (IOP). Increased IOP can harm optic nerve function through mechanical impacts and reduced blood flow. Conventional antiglaucoma drugs such as beta-blockers, carbonic anhydrase inhibitors and miotics have reduced preference due to local adverse effects and suboptimal IOP reduction. Traditional formulations have the drawback of poor bioavailability due to ocular barriers, accompanied by poor adherence.

Methods

This study focuses on the development of micellar systems by the thin film hydration method as drug vehicles to enhance ocular bioavailability for the management of glaucoma. Netarsudil-loaded micelles were loaded into temperature-sensitive in situ gels to further extend precorneal retention of the drug. The micelles were evaluated in terms of vesicle size, morphology, surface charge, pH and encapsulation efficiency.

Results

The optimized micelles, comprising poloxamer 407 (P407), displayed a particle size of 95.9 ± 4.826 nm, a zeta potential of -20.5 mV ± 2.506, PDI of 2.691 ± 0.0362 and an encapsulation efficiency of 66.4 ± 9.526%. Gelation studies indicated gelation at 37 °C for the developed formulation consisting of gellan gum and P407 in the ratio 1:3. The formed gels displayed a sustained in vitro release pattern. In vivo animal studies, notably on rabbit models, showcased sustained reduction in IOP compared to conventional formulations, extending therapeutic efficacy and duration of action.

Conclusion

Hence, the developed temperature-stimulated micellar gelling system showed potential as a promising carrier for ophthalmic drug delivery and for improved management of glaucoma.

Graphical Abstract

Purpose

This study aimed to develop and compare benzoyl peroxide (BPO)-loaded polymeric micelle formulations prepared via thin-film hydration (FT-BPO) and nanoprecipitation (FN-BPO) methods as potential topical carriers for acne vulgaris treatment.

Methods

Pluronic F127 and F68 were utilized as amphiphilic polymers, with the addition of sodium alginate and chitosan oligosaccharide lactate to enhance stability and antimicrobial efficacy. The formulations were characterized in terms of particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, physicochemical properties, stability, in vitro release, ex vivo permeation and skin retention, sprayability, and antimicrobial activity.

Results

The optimized FT and FN formulations exhibited particle sizes of 262.4 ± 15.5 nm and 355.2 ± 11.4 nm, respectively, with PDI values below 0.5 indicating homogeneous dispersions. The zeta potential shifted positively upon chitosan addition, supporting colloidal stability. The encapsulation efficiencies were above 89% for both formulations. In vitro release studies demonstrated higher cumulative release from FT-BPO compared to FN-BPO, whereas ex vivo studies revealed greater skin retention for FT-BPO and a slightly higher 24-h cumulative permeated amount (Qn) for FN-BPO, although both micellar formulations showed lower steady-state flux than free BPO. Sprayability assessments indicated wider spray distribution for FN formulations. Antimicrobial testing against Staphylococcus aureus showed larger inhibition zones with the FN formulation compared to commercial products. Stability studies highlighted better physicochemical stability of FT formulation under various storage conditions.

Conclusion

These findings suggest that both preparation methods yield effective BPO-loaded micellar systems with distinct release and permeation profiles, offering promising platforms for improved topical acne therapy.

Purpose

Formulation and process robustness are central to pharmaceutical development and commercial manufacturing, but development knowledge, monitoring signals, and routine records do not automatically become lifecycle manufacturing evidence. This study developed a structured framework for evidence qualification and decision routing across manufacturability, technology transfer, finished manufacturing, digital records, and continued verification.

Methods

A practice-oriented framework-development study used targeted source-domain mapping, concept extraction, explicit source-to-criterion derivation, generalized scenario application, and retrospective illustrative application to two publicly documented U.S. Food and Drug Administration (FDA) manufacturing cases. Each proposed criterion was traced to established pharmaceutical-development, manufacturing, validation, data-governance, or lifecycle-management concepts.

Results

The revised framework comprises four connected outputs plus seven structured qualification criteria addressing provenance/traceability, completeness/review, context, scientific or operational relevance, context-dependent corroboration, decision linkage, and residual uncertainty. Retrospective application to two public manufacturing cases illustrated different ways in which available information can remain insufficient for a defensible lifecycle decision when required review/routing is not operationalized or when risk relevance and residual uncertainty are handled inadequately. Generalized non-proprietary scenarios were retained as formative applications rather than empirical validation.

Conclusion

The framework provides structured criteria for organizing heterogeneous development and manufacturing information for lifecycle decisions while preserving clear limits on validation. Its contribution is an integrative evidence-qualification and decision-routing layer, not a replacement for product-specific validation, investigation, or regulatory assessment. Prospective product-specific evaluation remains necessary before implementation-effectiveness or predictive-validation claims can be made.

Purpose

Anacardium occidentale roots have traditional antidiabetic use, yet challenges such as poor solubility and limited bioavailability restrict their clinical applications. Nanoparticle-based delivery systems offer potential to overcome these limitations. This study aimed to develop and characterize zein–pectin nanoparticles encapsulating the polyphenol-rich column-purified 80% methanolic fraction of A. occidentale roots (FZPNP) and to evaluate their antioxidant and antidiabetic activities in vitro.

Methods

Zein–pectin nanoparticles (FZPNP) were prepared using antisolvent precipitation. Physicochemical properties were characterized by SEM, TEM, DLS, zeta potential, TGA, DSC, and FTIR. Encapsulation efficiency and in vitro drug release (24 h, pH 1.2, 6.8 and 7.4, 37 ± 0.5 °C) were assessed. Antioxidant capacity was determined by DPPH and ABTS radical scavenging assays, while antidiabetic potential was assessed using α-glucosidase inhibition.

Results

FZPNP demonstrated spherical morphology with a hydrodynamic diameter of 394.9 nm and a non-monodisperse size distribution. FZPNPs exhibited a negative zeta potential (-28.9 ± 1.4 mV) and a good encapsulation efficiency. Thermal stability was confirmed by TGA and DSC. The nanoparticles exhibited a pH-dependent, sustained, diffusion-controlled drug release profile. The FZPNPs retained significant antioxidant and α-glucosidase inhibitory activities.

Conclusion

Zein–pectin nanoparticles encapsulating polyphenol-rich A. occidentale root fraction exhibited favorable physicochemical characteristics and pH-dependent, sustained drug release while retaining significant antioxidant and α-glucosidase inhibitory activities. These findings suggest that the FZPNP formulation provides a promising nanocarrier system for enhancing the therapeutic efficacy of A. occidentale roots in managing diabetes and associated oxidative stress.

Purpose

Regulated life sciences manufacturing organisations face increasing pressure to adopt Industry 5.0 (I5.0) innovations while maintaining patient safety, product quality, data integrity, and regulatory compliance. Existing assessment models provide useful perspectives on technical maturity, expectation dynamics, and organisational innovation capability, but do not fully assess whether an innovation is ready to progress responsibly in a regulated, multi-stakeholder environment. This paper develops an I5.0 Innovation Readiness Framework and presents a preliminary practitioner-informed evaluation of its use in regulated life sciences manufacturing.

Methods

This paper uses design science research structured through the Double Diamond process. The framework was developed through literature review, advisory feedback, subject matter expert input, practitioner workshops, case-based application, surveys, and thematic analysis. Evaluation was conducted with a small, purposively selected cohort of 16 practitioners from a single educational-industry programme.

Results

The framework comprises three linked tools: the Innovation Maturity Assessment, Innovation Maturity Rubric, and Innovation Readiness Levels. Across two exploratory workshops involving 16 experienced practitioners, participants reported that the framework supported clearer discussion of readiness and improved visibility of adoption risks. In Workshop 2, descriptive feedback indicated that 91% of respondents viewed Innovation Readiness Levels as clearer than Technology Readiness Levels, 82% found the framework useful for comparing innovation timelines, and 75% would recommend it. These findings should be interpreted as preliminary practitioner feedback rather than sector-wide validation.

Conclusion

The findings support the conceptual distinction between innovation readiness and technology readiness and indicate the need to assess technical, regulatory, organisational, stakeholder, and societal dimensions together when evaluating I5.0 innovation in regulated manufacturing. Further evaluation with broader industry cohorts, quality and regulatory professionals, and regulatory stakeholders is required.

Cutaneous fungal infections (CFIs) are among the most common skin disorders and often require prolonged topical therapy. However, conventional topical antifungal formulations frequently exhibit poor aqueous solubility, inadequate skin permeation, and limited drug retention, resulting in suboptimal therapeutic outcomes. The present study aimed to develop and optimize an isoconazole nitrate-loaded nanostructured lipid carrier (NLC) gel using a Quality by Design (QbD) approach to enhance topical antifungal delivery. A systematic risk assessment followed by a 3² full factorial design was employed to optimize lipid mixture and surfactant/co-surfactant concentrations using particle size and drug loading as critical quality attributes. The optimized formulation (P1) exhibited a particle size of 93.3 ± 1.2 nm, zeta potential of − 20.2 mV, entrapment efficiency of 97.41 ± 0.42%, and drug loading of 4.871 ± 0.031%, with excellent agreement between predicted and experimental responses. The optimized NLC dispersion was incorporated into a 0.5% Carbopol 940 gel, which demonstrated acceptable physicochemical properties, including pH (6.3 ± 0.005), viscosity (2574 ± 65 cps), spreadability (4.49 g·cm/s), extrudability (4.38 ± 0.18%), and drug content (97.18 ± 0.71%). The formulation exhibited sustained in vitro drug release (72.55% over 12 h) following first-order kinetics (R² = 0.9959) and significantly enhanced ex vivo skin permeation (98.49% at 7 h) compared with the conventional gel. Antifungal evaluation against Candida albicans demonstrated superior activity of the NLC gel, producing a larger inhibition zone (22 ± 0.1 mm at 10 mg/mL) than the marketed formulation (17 ± 0.8 mm). The formulation also satisfied microbial quality requirements and remained stable during three months of accelerated stability testing. Overall, the QbD-optimized isoconazole nitrate-loaded NLC gel represents a promising topical delivery system with improved physicochemical characteristics, enhanced skin permeation, sustained drug release, and superior antifungal efficacy for the management of cutaneous fungal infections.

Graphical Abstract

Conventional quality evaluation of traditional Chinese medicine (TCM) pills relies mainly on chemical markers and compendial tests, with limited consideration of the physical microstructure of the finished dosage form. This study aimed to investigate whether imaging-derived microstructural characteristics could provide supplementary descriptors for quality-related characterization of complex herbal solid dosage forms using Liuwei Dihuang pills as a representative model. Water pills (WP), water-honey pills (WHP), honey pills (HP), and concentrated pills (CP) were characterized by scanning electron microscopy (SEM), fluorescence imaging (FL), and micro-computed tomography (micro-CT), combined with quantitative image analysis. SEM revealed a progressive transition from the loose and particulate structure of WP to the more compact matrix of WHP and the continuous matrix of HP, demonstrating the marked influence of binder composition on pill microstructure. Imaging-derived parameters further differentiated commercial products from different manufacturers and revealed measurable batch-to-batch variability. In controlled formulations, fluorescence intensity at Ex/Em 675/740 nm increased with refined-honey content (R² = 0.9991) and was altered by prolonged drying, while SEM and fluorescence imaging distinguished structural and compositional differences caused by honey refining and binder substitution. Micro-CT provided complementary information on internal low-attenuation regions and edge distributions among different pill types. Importantly, the complete disintegration time of commercial WHPs, ranging from approximately 18 to 40 min, was positively correlated with the SEM-derived area occupancy rate (R² = 0.7144) and fluorescence intensity (R² = 0.6279). These findings demonstrate that multimodal imaging can capture formulation- and manufacturing-related physical variability in complex solid dosage forms and suggest the potential value of imaging-derived descriptors for supplementary product characterization, subject to broader validation.

Migraine is a common neurological condition often associated with nausea and vomiting. Conventional oral medications often are difficult to take and absorb during migraine attacks, as nausea and vomiting tend to accompany them. The objectives of the present study were to design and characterize a sublingual film containing Diclofenac Potassium (DK) and Ondansetron Hydrochloride (ONH) loaded Chitosan Nanoparticles (CS-Np) in the same dosage form. Particles of ONH were loaded into chitosan nanoparticles by ionic gelation and the particles were characterized in terms of particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The optimized nanoparticles exhibited a mean size of 130 ± 2.0 nm, PDI of 0.13 ± 0.01 and a zeta potential of about + 10 mV with an entrapment efficiency of 78.4 ± 2.6%. DK was incorporated into HPMC E15-based sublingual films and nanoparticles were added to these. The films were assessed for physical properties, drug content uniformity, disintegration time, in vitro drug release, ex vivo permeation and short-term stability. The optimized formulation (NSF2) exhibited rapid DK release (57% released within 6 min) while ONH release from nanoparticle containing system was 75.5% after 12 h under in vitro test conditions. The permeation of ONH across goat sublingual mucosa was studied ex vivo separately for 12 min and the optimized formulation exhibited ~ 65% of cumulative permeation at the end of the study period. The measured physicochemical characteristics, drug content and drug release profile of the optimized films were maintained during the three-month stability study under the tested storage conditions. The results show that it is possible to develop a sublingual film containing DK directly incorporated into the film and nanoparticles of ONH loaded in it with different release properties. Additional kinetic, dynamic, safety and clinical trials are needed to confirm in vivo efficacy and clinical significance of formulation.

Graphical Abstract