Drug Development and Industrial Pharmacy最新文献

Background: Metformin is gold standard for polycystic ovary syndrome (PCOS), but associated with gastrointestinal side effects, leading to poor patient adherence. Present oral fast-dissolving films (OFDFs) offer rapid disintegration, improving drug delivery, therapeutic outcomes, and patient compliance.

Objective: This project aimed to fabricate metformin-loaded OFDFs to enhance patient compliance and drug efficacy in treatment of PCOS.

Methods: Metformin-loaded OFDFs were prepared using solvent casting method with hydroxypropyl methylcellulose (HPMC) and gelatin as film-forming polymers and propylene glycol as a plasticizer. The Box-Behnken experimental design was utilized for optimization. Various physico-chemical characterization tests, including thickness, weight, folding endurance, percent elongation, water content, and moisture uptake, were conducted. In vitro drug release, disintegration time, and mechanical strength were analyzed. Additionally, a pharmacokinetic study in rats was conducted to compare plasma concentrations of optimized formulation with those of metformin intragastric solution.

Results: A stable drug-loaded formulations with a uniform surface and an amorphous nature of drug were prepared in OFDFs. The optimized formulation demonstrated significant drug release at 5 min (98.9%), a rapid disintegration time (19.2 sec), and good mechanical strength (7.4 MPa) (ANOVA, p < .05). Furthermore, increased values of C_max as well as AUC_0-t were also observed in plasma of rats treated with optimized formulation (MF7) as compared to those administered with metformin intragastric solution (Student t-test, p < .05).

Conclusion: Results cemented a very rapid disintegration and dissolution of OFDF, suggesting a promising substitute to enhance patient adherence and reduce metformin onset time in treating PCOS.

Objective: The main objective of this article was to explore the therapeutic potential of intranasally administered metal/metal oxide nanoparticles (NPs) for treating central nervous system (CNS) disorders. Significance of review Metal/metal oxide NPs offer new possibilities for brain imaging and targeted drug delivery. These NPs can be delivered intranasally with minimal invasiveness, offering a patient-friendly approach for therapeutic applications. The current article synthesizes research studies on the potential of intranasal metal/metal oxide NPs for treating CNS disorders, focusing on their unique features, transport pathways, therapeutic and diagnostic benefits, and neurotoxicological challenges.

Key findings: The small size and high surface area of metal/metal oxide NPs enable efficient drug encapsulation and direct delivery to the brain via the olfactory and trigeminal pathways, bypassing the blood-brain barrier. These NPs exhibit tunable surface chemistry, allowing functionalization with ligands or coatings to enhance biocompatibility and reduce neurotoxicity. Additionally, these NPs can show inherent therapeutic properties, such as antioxidant or anti-inflammatory effects, which further support neuroprotection.

Conclusions: Intranasal delivery of metallic NPs is an emerging strategy for drug delivery and imaging, particularly for targeting CNS disorders. However, the development of novel NPs with minimal neurotoxicity is crucial to ensuring their safety and efficacy for clinical applications.

Objective: This review article outlines the transformative impact of Artificial Intelligence (AI) in the pharmaceutical sciences, focusing on its integration with modern technologies and its role in advancing medication research, development, production, and digital transformation.

Significance: AI, through its synergy with machine learning (ML), deep learning (DL), and Industry 4.0 technologies such as the Internet of Things (IoT), robotics, blockchain, and digital twins, is pivotal in advancing personalized healthcare and adaptive manufacturing processes.

Methods: This article reviews AI technologies to analyze complex datasets, enhancing real-time decision-making, predictive analytics, and supply chain optimization. This approach allows for the development of personalized medicines using genomic, clinical, and environmental data.

Results: The application of AI has significantly improved operational efficiency and facilitated the tailored production of medications. However, challenges such as data privacy, algorithmic bias, and the need for updated regulations remain prevalent.

Conclusions: Addressing these issues through ethical frameworks and comprehensive training is essential. The ongoing evolution of AI promises to bolster digital transformation, promote sustainable manufacturing, and improve global healthcare outcomes, setting a course toward innovation and patient-centric solutions in pharmaceutical sciences.

Objective: The aim of this work was to formulate and develop LEV loaded nanospheres in situ nasal gel.

Significance: This is an efficient therapy for epilepsy via brain targeting to increase bioavailability and reduce the dose frequency.

Method: This study looked at the impact of process factors (polymer amount (mg) (50,7 5, and 100), poloxamer 188 concentration (0.5, 1, and 1.5), and polymer type (Eudragit S100, Eudragit L100, and Eudragit RS 100)) on the responses (particle size (nm), entrapment efficiency (%), and zeta potential (mV) in order to optimize LEV-loaded nanospheres utilizing Box-Behnken design. The design expert software was used to perform the process of optimization categorically. Using the nanoprecipitation process, LEV-loaded nanospheres were effectively formulated, which were then evaluated by FTIR and DSC for drug-polymer interaction, TEM, zeta potential, and particle size.

Results: The optimized nanospheres formulation, which had the composition of 100 mg Eudragit S100 and 1.5% poloxamer 188, showed a particle size of 79.07 nm, % entrapment efficiency of 99.74%, and a zeta potential of -40.6 mV. DSC thermogram and FTIR spectrum showed no interaction between drug and polymer used. TEM image indicates spherical shape of the nanosphere formulation, LEV-loaded nanospheres in situ nasal gels were prepared using Na CMC at different concentrations (0.5, 1, and 1.5). NG3 (1.5% NaCMC) showed the best characterization of in situ nasal gel (gelation time of 18 s, gelation temperature of 28.6 °C and % drug release of 73%). In ex-vivo permeation study, the amount of LEV permeated from LVT loaded nanospheres in situ nasal gel (NG3) and the plain LVT in situ nasal gel were 75.5 and 67.8, respectively. NG3 confirmed higher permeability so it was chosen for in vivo pharmacokinetic study. It showed absolute bioavailability five folds greater than the IV route of administration.

Conclusions: LEV-loaded nanospheres in situ nasal gels enhanced its tissue permeability and pass BBB directly which bypass the first pass metabolism in liver. So the bioavailability increases.

Significance: The liposomal formulation reveals a safe, sustained, and efficient ocular drug delivery to improve the therapeutic potential of dorozolamide hydrochloride in glaucoma treatment.

Objective: A liposomal formulation of Dorzolamide hydrochloride was developed and evaluated for sustained ocular delivery with improved permeation and safety.

Methods: Liposomes were prepared using the thin-film hydration method and optimized through a 3² full factorial design, analyzing the effects of phosphatidylcholine and cholesterol on entrapment efficiency and drug release via response surface methodology.

Results: The optimized formulation, containing 200 mg phosphatidylcholine and 40 mg cholesterol, exhibited a vesicle size of 98.22 ± 10.03 nm, zeta potential of -21.53 ± 1.02 mV, and high entrapment efficiency (97.5%). In vitro studies confirmed sustained drug release over 8 h, while ex vivo transcorneal permeation was 1.8 times greater than that of marketed eye drops. Safety assessments using Hen's Egg Test-Chorioallantoic Membrane(HET-CAM) and Draize tests established the formulation as nonirritant and isotonic.

Conclusion: Overall, the liposomal system significantly enhanced ocular bioavailability and demonstrated potential as a safe and effective option for long-term glaucoma therapy.

Objective: The primary objective of this review is to comprehensively analyze advancements in novel drug delivery systems, including carrier-based approaches, M cell targeting, and controlled and sustained release formulations, which have been developed to improve iron bioavailability and minimize gastrointestinal side effects commonly associated with conventional iron therapies.

Significance: Iron deficiency anemia is a widespread health issue, disproportionately affecting women, children, and vulnerable groups, with serious maternal and population health impacts. This review includes current research, clinical trials, and patented inventions to illustrate the advantages, limitations, and potential future directions of these technologies used in managing IDA. Understanding these advanced systems is crucial for developing safer and more effective iron formulations.

Key findings: Advanced drug delivery system including carriers such as liposomes, hydrogels, microspheres, nanoparticles, solid lipid nanoparticles, and sucrosomial iron. They significantly increase intestinal absorption and systemic availability of iron compared to conventional therapies. M cell targeting enhances iron absorption by facilitating efficient transcytosis across the intestinal epithelium, leading to improved bioavailability. Additional benefits from controlled release and gastroretentive dosage forms, which maintain release at absorption sites while reducing adverse effects.

Conclusion: Novel drug delivery systems represent a transformative approach in iron supplementation therapy, overcoming the dual challenges of poor bioavailability and gastrointestinal intolerance. By optimizing delivery, absorption, and release kinetics, these systems enhance therapeutic efficacy and patient acceptability. Ongoing research and clinical trials of such technologies hold great promise for developing next-generation iron formulations with enhanced bioavailability, superior safety, and effectiveness profiles.

Objective: This study aimed to develop and evaluate nanostructured lipid carrier (NLC) gel loaded with rofecoxib (ROX) for topical treatment of rheumatoid arthritis (RA), minimizing systemic exposure and cardiotoxicity.

Significance: Despite its withdrawal due to cardiovascular risk, ROX remains a potent COX-2 inhibitor. Reformulating it into a localized NLC delivery system could enable safe therapeutic application in RA by targeting inflamed joints with minimal systemic effects.

Method: A Box-Behnken design optimized lipid content, surfactant concentration, and sonication time to achieve minimal particle size, high entrapment efficiency, and stable zeta potential. The optimized formulation was incorporated into a gel and evaluated for physicomechanical properties, drug release, and in vivo performance in a complete Freund's adjuvant (CFA)-induced arthritic rat model. Radiographic, histopathological, and biodistribution studies were conducted.

Results: Optimized ROX-NLCs exhibited particle size of 225 nm, entrapment efficiency of 90.65%, PDI of 0.265, and zeta potential of -38 mV, with good stability and gel compatibility. In vitro drug release followed Higuchi and Korsmeyer-Peppas kinetics, showing higher cumulative release compared to plain ROX gel and oral ROX. In vivo, ROX-NLC gel significantly reduced paw swelling and arthritis scores, preserved joint architecture, and avoided cardiac alterations observed with oral ROX. Biodistribution confirmed negligible systemic drug levels (below LOD: 0.079 µg/mL).

Conclusion: ROX-NLCs gel provides a safe, sustained, and effective topical delivery system for RA therapy, enhancing local efficacy while reducing systemic cardiotoxic risk.

Objectives: Enoxaparin (ENX), an anticoagulant, was developed as a topical aqueous spray that provides rapid treatment for contusions by dissolving micro-clots, reducing inflammation, and thereby alleviating pain and edema.

Significance: This spray offers rapid relief of contusions, improves drug retention in the skin, and helps to restore the aesthetic appearance of injured skin.

Methods: ENX aqueous sprays were developed using an aqueous dispersion method with medium-chain triglycerides (MCTs) as permeation enhancers and propylene glycol (PG) used as a plasticizer. Two optimized formulations, F_A9 (caproic acid-based) and F_B8 (caprylic acid-based), were selected using a Box-Behnken design via surface response methodology. The various physicochemical and spray characteristics of optimized formulations were evaluated, and therapeutic efficacy was assessed in a contusion-induced animal model.

Results: The optimized formulations (F_A9 and F_B8) exhibited favorable drying time and transparency for topical applications. Drug deposition was significantly higher in F_A9 (47.68% ± 4.61) and F_B8 (38.25% ± 3.76) compared to the marketed formulation (31.52% ± 2.37). The in vivo animal study indicated that F_A9 facilitated complete bruise resolution after five days in contusion-induced animals, whereas F_B8 required one week to recover. Histological analysis confirmed rapid vascular and tissue recovery with F_A9, while F_B8 exhibited moderate healing due to deeper tissue injury, but optimized formulations healed faster than the marketed preparation.

Conclusions: The ENX aqueous spray containing MCTs demonstrated high therapeutic efficacy and faster bruise resolution than the marketed formulation, thus presenting a promising alternative for the topical treatment of contusions.

Objective: This study aimed to develop and evaluate a dermal gel formulation incorporating the methanolic leaf extract of Guiera senegalensis (GS) for potential topical antimicrobial application.

Significance: Dermal gel formulations of GS leaf extracts may offer safe and effective alternatives against bacterial and fungal skin infections, particularly beneficial for pediatric and geriatric individuals who are most susceptible to such conditions.

Methods: Leaves of GS were extracted by maceration using methanol and fractionated with solvents of increasing polarity. The extract and fractions underwent phytochemical screening, antibacterial evaluation, and spectral characterization (GC-MS and FT-IR). Xanthan gum-based gels were formulated and evaluated for pH, viscosity, spreadability, extrudability, swelling, erosion, and antibacterial activity.

Results: The methanolic extract (26.36% yield) contained abundant phytochemicals, including flavonoids, phenolics, tannins, and terpenoids. Fractionation revealed the polarity-based distribution of phytochemicals but did not enhance antibacterial potency. The methanolic extract showed the strongest activity against Staphylococcus aureus (22.24 ± 0.12 mm). GC-MS and FT-IR confirmed the presence of bioactive compounds and functional groups linked to antimicrobial effects. The gels exhibited skin-compatible pH (5.95-6.65), appropriate viscosity (11.23-63.23 Pa·s), and desirable spreadability. Among all, formulation F2 showed the best overall characteristics for topical use.

Conclusion: GS leaf extract-loaded gels demonstrated excellent physicochemical properties and antibacterial activity. Although fractionation provided no added antimicrobial advantage, it offered insights into phytochemical distribution. Formulation F2 represents a promising natural, plant-based topical antimicrobial candidate.

Objective: The objective of this study was to develop a stable clear ophthalmic nano-micellar formulation of Nepafenac.

Significance: The current marketed suspension formulation of nepafenac indicated for post-surgical uveitis is associated with higher manufacturing complexity and cost due to the need for sterile drug substance and specialized aseptic processing inherent to suspension-based ophthalmic products. It also exhibits limitations in patient compliance due to relatively high viscosity, lacrimation, and foreign body sensation following instillation.

Methods: Pre-formulation study was done to identify the excipients required. Systematic changes in the concentration of surfactant and crystal inhibitor along with other excipients led to the development of stable nano-micellar formulation. Box-behnken method was used for the optimization. The optimized micellar composition was evaluated for physicochemical tests particle size, zeta potential, cloud point, osmolality pH, assay of drug, entrapment efficiency and dynamic viscosity. Further in-vitro cell viability, in-vitro release, ocular tolerance test and stability evaluation were also performed.

Results: Average particle size of the micelle ranged from 10 to 20 nm, 43.5 mPas dynamic viscosity, osmolality of 319 mOsm/Kg, pH 7.4 and cloud point of 59.7 °C. The optimized formulation demonstrated in-vitro safety as confirmed by MTT cell viability and HET-CAM ocular irritation assays, and exhibited physicochemical stability for up to 6 months under real-time storage conditions.

Conclusion: The optimized micelle formulation can serve as a better alternative for ophthalmic delivery of nepafenac.