Drug Development and Industrial Pharmacy最新文献

Objective: To design and optimize a TPGS-stabilized polymeric micellar system for Cabotegravir (CAB), strategically addressing its dissolution-rate and permeability constraints to potentiate oral bioavailability and maximize antiretroviral therapeutic outcomes.

Significance: CAB, a potent HIV-1 integrase strand transfer inhibitor, suffers from dissolution-rate limitations and P-glycoprotein efflux, restricting oral utility. Incorporation of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) enables superior solubilization, enhances intestinal translocation, and circumvents efflux transporters, offering a transformative, non-invasive alternative to parenteral antiretroviral regimens while reinforcing patient adherence and therapeutic efficacy.

Methods: CAB-loaded micelles were fabricated via the thin-film hydration technique and systematically optimized using a 3² full-factorial design by modulating TPGS concentration and rotary evaporation speed to minimize particle size and maximize drug encapsulation. The optimized formulation underwent physicochemical characterization, including particle size, polydispersity index (PDI), zeta potential, and surface morphology. In vitro drug release was examined, followed by in vivo pharmacokinetic profiling in Wistar rats.

Results: The optimized micellar system demonstrated a mean particle size of 95.16 ± 0.12 nm, PDI of 0.411 ± 0.24, zeta potential of -4.72 ± 1.05 mV, and an exceptional encapsulation efficiency of 96.26 ± 1.21%. Compared to conventional CAB suspension, the TPGS-based micelles exhibited markedly enhanced dissolution kinetics and a 236.75 ± 0.74% increase in relative oral bioavailability, accompanied by prolonged systemic circulation.

Conclusion: TPGS-enabled micellar encapsulation significantly enhances the oral delivery profile of CAB, offering a promising, non-invasive, and patient-compliant alternative to parenteral antiretroviral regimens, potentially improving therapeutic outcomes in HIV management.

Objective: This study prepared a geraniol (Ger)/hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex (IC) and evaluated its acute toxicity in mice to support applications in functional foods and pharmaceuticals.​.

Significance: Poor stability and irritation limit Ger use; HP-β-CD complexation improves stability, controls release, and reduces toxicity.

Methods: Response surface methodology optimized IC preparation, while SEM, XRD and other methods confirmed formation. Thermal stability and in vitro release were tested, and intramuscular acute toxicity in mice determined LD₅₀.

Results: Optimal conditions were 100 mg/mL HP-β-CD, 20% acetonitrile, and 35.6 °C, achieving 73.08% encapsulation efficiency. The IC retained over 80% efficiency after 25 days at 4, 25 and 50 °C and showed sustained release (90% at 8 h vs. 2 h for free Ger). The IC LD₅₀ was 2373.96 mg/kg, higher than 1932.49 mg/kg for free Ger, with no major organ lesions.

Conclusion: Ger/HP-β-CD IC exhibits sustained-release properties and better safety than free Ger. It is an effective Ger delivery system and supports its potential development and application in functional foods and drugs.

Objective: The present study created nimesulide-loaded in situ gels and assessed their potential application in ocular inflammation.

Methods: Because in situ gels have a low viscosity, sodium alginate, and hydroxypropyl methylcellulose combined to create a nimesulide CD complex that is easy to apply. However, due to the gelation creation with pH, washing and removing it from the ocular surface becomes challenging. Production was carried out using different ratios of sodium alginate, hydroxypropyl methylcellulose, and hyaluronic acid.

Results: Characterization studies led to the determination of the optimized formulation. The optimized formulation viscosity pH 5.5 = 547.3 ± 76cP, viscosity pH 7.4 = 8798.3 ± 254 cP, and pH = 5.4 ± 0.01 were obtained. In in vitro release experiments, approximately 53% of nimesulide was released by burst action within 2 h, followed by a controlled release over 12 h. Mathematical modeling of the formulations' release kinetics revealed that they were consistent with the Korsemeyer-Peppas and Weibull models. It was determined that nimesulide-loaded in situ gels showed over 80% viability in the L929 cell line. Rats underwent no adverse conditions in Draize's in vivo experiment.

Conclusion: For this reason, the TB5 formulation may be a good choice when treating ocular inflammation. These findings may be supported by future efficacy studies using this formulation.

Introduction: This study aimed to develop and validate a rapid, accurate, and robust RP-HPLC method for the simultaneous quantification of Selegiline (SEL) and Biochanin A (BCA) in bulk and in self-nanoemulsifying drug delivery system (SNEDDS). Developing a validated analytical method for the novel SEL-BCA combination is important for ensuring precise quantification of the combination's potential applicability in Parkinson's disease (PD) management.

Methods: Chromatographic separation was performed using an Agilent 1220 Infinity II HPLC system equipped with a 5TC-C18(2) column (250 × 4.6 mm, 5 µm) and a variable wavelength detector (VWD). An isocratic mode with mobile phase of acetonitrile (ACN) and water containing 0.1% o-phosphoric acid (50:50 v/v) was used at a flow rate of 1 mL min^-1, with detection at isosbestic wavelength of 208 nm. Validation followed ICH Q2(R1) guidelines. SEL-BCA SNEDDS was formulated and characterized for particle size and PDI, and the validated method was applied to quantify in vitro drug release and % drug assay.

Results: The method displayed excellent linearity over the 0.4-50 µg mL^-1 concentration range, with correlation coefficients of 0.9997 for SEL and 0.9995 for BCA. System suitability parameters, including tailing factor < 1.5, resolution > 2, and theoretical plates > 2000, were satisfactory. The method remained robust despite small variations in flow rate, column temperature, injection volume, wavelength, and mobile phase composition. The developed SNEDDS presented a particle size of 120.3 nm and a PDI of 0.1925.

Discussion: A simple, sensitive, and robust RP-HPLC method was successfully developed and validated for the concurrent estimation of SEL and BCA in bulk drug and SNEDDS.

Objective: Ferulic acid (FA) exhibits antioxidant and metabolic regulatory properties; however, its clinical translation in obesity management is limited by poor aqueous solubility, low permeability, and rapid systemic clearance (BCS class IV).

Significance: To develop and optimize a chitosan-conjugated hybrid polymer-lipid nanocarrier system to enhance the oral bioavailability of FA and evaluate its anti-obesity efficacy via oxidative stress-mediated metabolic modulation.

Methods: FA-loaded nanocarriers were prepared using emulsification solvent-evaporation followed by probe sonication and optimized through central composite design (17 experimental runs). Physicochemical characterization included particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, drug loading, and in vitro release kinetics. Anti-obesity efficacy was assessed in a high-fructose diet-induced obese Sprague-Dawley rat model (n = 6 per group). Data were expressed as mean ± SD and analyzed using two-way ANOVA followed by Tukey's post hoc test (p < 0.05).

Results: The optimized formulation (F8) exhibited a mean particle size of 110.3 ± 0.2 nm, PDI of 0.241 ± 0.02, zeta potential of -37.21 ± 0.21 mV, encapsulation efficiency of 86.96 ± 4.4%, and drug loading of 17.39 ± 3.2%. Sustained drug release of 80.24 ± 2.6% was observed over 24 h, following Korsmeyer-Peppas kinetics (R² = 0.99; n = 0.4). In vivo administration significantly reduced plasma insulin (5.84 ± 0.42 to 1.21 ± 0.18 ng/mL), total cholesterol (186.4 ± 8.7 to 97.9 ± 6.3 mg/dL), triglycerides (168.2 ± 7.9 to 98.7 ± 5.8 mg/dL), and LDL (121.5 ± 6.4 to 44.9 ± 4.2 mg/dL), while increasing HDL (38.6 ± 3.1 to 49.8 ± 2.9 mg/dL) compared with high-fructose controls (p < 0.05). Anti-obesity evaluation revealed significant reductions in oxidative stress markers and improved lipid profile: 4.8-fold reduction in insulin, 1.9-fold decrease in cholesterol, 1.7-fold reduction in triglycerides, 1.2-fold increase in HDL, and 0.37-fold reduction in LDL (p < 0.05). These effects were accompanied by attenuation of oxidative stress markers, suggesting restoration of redox-sensitive metabolic pathways.

Conclusion: The chitosan-conjugated hybrid polymer-lipid nanocarrier significantly enhanced systemic exposure and metabolic efficacy of FA, demonstrating sustained antioxidant-mediated improvement in insulin sensitivity and lipid homeostasis. This nano-enabled strategy represents a promising oral therapeutic platform for obesity-associated metabolic dysfunction.

Objective: The objective of this study was to develop and optimize Clausena anisata leaf extract (CLE) lozenges, a smoking cessation aid, using a Quality by Design (QbD) approach.

Significance: Optimized CLE lozenges offer a scalable, stable herbal smoking-cessation formulation.

Methods: The quality target product profile (QTPP) was defined, critical quality attributes (CQAs) were identified, and an initial risk assessment was performed. The formulation development of CLE lozenges was designed using a Box-Behnken design, incorporating three factors: compression force, microcrystalline cellulose content, and sodium starch glycolate content.

Results: The results indicated that the optimal formulation contained 10% microcrystalline cellulose and 2% sodium starch glycolate, with a compression force of 2000 psi, yielding desirable physical properties, including hardness of 4-6 kgf, friability ≤1%, and disintegration time ≤30 min. This formulation was subsequently scaled up for trial production at a manufacturing site. The trial batch exhibited slight variations in some physical properties but remained within the defined design space. Moreover, the nitrate content and assay results between the laboratory-scale and trial-scale batches were comparable. The trial-scale batch completely dissolved within 1 h. Stability studies demonstrated that the lozenges were more stable when stored in aluminum foil bags with a heat seal than in polyethylene terephthalate (PET) bottles under both 30 °C/75% RH and 40 °C/75% RH conditions for six months.

Conclusions: This study successfully developed and optimized CLE lozenges using the QbD approach. The results suggest that this herbal product can be further scaled up to pilot and production levels for potential use as a smoking cessation aid.

Objective: This study explores the development of intravaginal rings with controlled drug release, fabricated through injection molding, for the treatment of viral and bacterial gynecological diseases such as HIV/AIDS, cervical cancer caused by HPV, and other infections.

Significance: Recent advancements in women's health treatments have been driven by technological innovations and clinical improvements, where the development of new technologies for treating and preventing cancers and infections in women highlights a gap that still requires significant improvement.

Methods: The selected drugs were copper sulfate (CuSo₄), silver sulfadiazine (AgSD), and fluorouracil (FU), which offer a combination of antibacterial, antifungal and antiviral properties. Devices were manufactured from Low Density Polyethylene (LDPE) polymer with 20% (w/w) of each drug isolated. Multi-drug devices were produced with combinations of 15% copper sulfate and 15% silver sulfadiazine, and 15% silver sulfadiazine and 15% fluorouracil. Characterization to evaluate the safety and effectiveness of the devices was performed through SEM, FTIR, DSC, DMA, and in vitro drug release tests.

Results: Preliminary results suggest that drug release was sustained for more than 40 days, with high drug incorporation capacity, and high process reproducibility, with LDPE mechanical properties minimally affected.

Conclusion: This study demonstrates the feasibility of using injection molding to produce multidrug LDPE intravaginal rings with stable mechanical properties, drug-loading capacity, and sustained release, highlighting a promising and scalable platform for future therapeutic and prophylactic applications in women's health.

Objective: This study aimed to leverage nano-liposomes (NLs) for optimizing the solubility, bioavailability, and pharmacokinetic profiles of 7-hydroxy-5-methoxy-6,8-dimethyl flavanone (7-HMDF), 5,7-dihydroxy-6,8-dimethyl-flavanone (HMF), 2,4-dihydroxy-6-methoxy- 3,5-dimethylchalcone (DMC), betulinic acid (BA), and ursolic acid (UA) derived from the standardized ethanol extract (EE) and supercritical fluid extract (SFE) of Syzygium campanulatum Korth leaves.

Significance: This study provides a comprehensive/validated approach for the nano-pharmaceutical development of poorly bioavailable phytomedicines.

Methods: NLs encapsulating BA, DMC, EE, and SFE were prepared (thin-film hydration method), optimized, and subsequently characterized. Besides, 6-months stability test, NL-EE and NL-SFE also underwent oral pharmacokinetic evaluation using Sprague-Dawley (SD) rats.

Results: HPLC analysis revealed higher concentration of marker compounds within SFE as compared to EE and in silico ADME-Tox profiling predicted safe and favourable pharmacokinetics of those marker compounds. Additionally, NLs demonstrated optimum size (70 238nm), polydispersity index (0.250.43), zeta potential (-28 to -49 mV), encapsulation efficiency (4065%), in vitro drug release, and six months stability. Shelf-life was temperature-dependent, with BA stable at 25°C and DMC moderately stable, but both declined sharply at 60 °C. NLs encapsulation noticeably increased the aqueous solubility of the marker compounds by 50%. Finally, in vivo pharmacokinetic evaluation confirmed the presence of 7-HMDF, HMF, and DMC in rats' plasma, indicating improved absorption, prolonged circulation, enhanced bioavailability, and sustained release of NLs as compared to their non-liposomal counterparts (EE/SFE).

Conclusions: NL encapsulation significantly enhanced the solubility, entrapment efficiency, oral bioavailability, and pharmacokinetic profiles of 7-HMDF, HMF, and DMC from S. campanulatum extracts, demonstrating NLs as promising drug delivery systems.

Objective: To analyze drug's physicochemical properties and dissolution profiles of testosterone tablets compressed with two different load levels (2 and 15 tons) and to evaluate the influence of process additive on tablet properties.

Significance: Testosterone implants are inserted in the subcutaneous tissue and follow a superficial erosion process that leads to drug absorption during 4 to 5 months. Testosterone is a cholesterol derivative with an anhydrous form as their most stable structure, although another two hydrated polymorphic forms were also identified. Due to the fact that compression processes may induce polymorphic changes in some API, which can lead to different dissolution behavior, a study of physicochemical properties and polymorphic changes are important to tablet manufacturing.

Methods: Tablets were manufactured by compression molding with a hydraulic press and analyzed by DSC, XRD, SEM, FTIR and drug dissolution tests.

Results: It was observed that 15 tons represented an excessive load, resulting in a fragile tablet with lamination and cracks. DSC analysis indicated the presence of structural water, although XRD patterns indicated that the drug was in its anhydrous form. FTIR also revealed water presence, but not an indicative of a monohydrate structure. Dissolution tests suggested the applied load and process additive may have some minor influence on dissolution profile, although they are not the main attributes influencing tablet dissolution.

Conclusions: This study provides insight on how compression load and process additive influences API properties and tablet behavior, showing the importance of these factors while developing a tablet manufacturing process.