Journal of Pharmaceutical Innovation最新文献

Purpose

Moisture-Activated Dry Granulation (MADG) is a tablet manufacturing method developed from wet granulation method. MADG methods are more efficient and cost-effective in the production of solid dosage forms since they use less fluid and shorter tablet manufacturing time. The MADG method could also be used for water-sensitive or heat-sensitive products where traditional methods may not be suitable. MADG tablet manufacturing is divided into an agglomeration step to activate the granule formation and a moisture absorption step to absorb excess moisture from the granule. This research aims to determine the effect of MADG method on the physical quality of tablet mass and tablet of ethanol–water roasted Agung banana var. Semeru peel extract (RBPE) compared to wet granulation method.

Methods

The tablets were prepared by using wet granulation and MADG method.

Results

Through the statistical analysis, the granules manufactured using MADG and wet granulation methods have a similar flowability, but those manufactured using MADG method have a higher moisture content. Tablets manufactured using MADG and wet granulation methods have a similar hardness. On the other hand, tablets manufactured using MADG method have lower friability and easier to be disintegrated compared to tablets manufactured using wet granulation method.

Conclusion

The experimental data shows that MADG is a better method than wet granulation in manufacturing RBPE tablets.

Purpose

Certain oils like butter oil and sesame oil have been traditionally used to reduce inflammation. The objective of the study was to use these oils for the formulation of microemulsion based gel containing capsaicin so as to give synergistic effect.

Methods

Solubility studies of capsaicin were done in oils, surfactants and cosurfactants. Pseudoternary phase diagram was constructed to identify the ratio of surfactant to cosurfactant. Capsaicin-loaded microemulsion was formed using water titration method. The microemulsion was evaluated for globule size, polydispersibility index, zeta potential, % drug content and in vitro drug release. The desirable microemulsions were converted to gel using Carbopol 934P. The microemulsion based gels were studied for viscosity, spreadability, pH, % drug content and in vitro drug diffusion. These gels were further tested for % drug permeation through rat skin, skin irritation and anti-inflammatory activity using rat paw oedema method and stability.

Results

Butter oil, cod liver oil and sesame oil were selected as oil components, Tween 80 and polyethylene glycol 400 (PEG 400) were identified as surfactant and cosurfactant respectively. Microemulsions formed using these components were loaded with capsaicin and screened to identify compositions that gave small globule size and lower values of PDI. The so formed micromulsion had globule size of less than 200 nm and zeta potential of around − 20mV. Microemulsions were then formed in to gel using 1% Carbopol 934P. Butter oil-based microemulsion gel had higher anti-inflammatory effect and lower values of primary irritation index as compared to other gels. All the transemulgels remained stable over a period of 1 month.

Conclusion

Caspsaicin-loaded, butter oil based microemulsion gel shows promise as topical delivery system for anti-inflammatory activity.

Background

Rivastigmine (RT), exhibits low oral availability (40%) and high hepatic first-pass (36%). Circumventing the blood-brain barrier-related convolutions for successful brain delivery following intranasal administration prerequisites nano-size particles with high drug loading due to restriction on the quantity administrable through this route. Also, mucoadhesion of nanoparticles (NPs) to nasal mucin is required to counter their ephemeral residence due to rapid mucociliary clearance in order to sustain drug release over a prolonged period. Therefore, the selected polymer should confer these attributes to the NPs for optimized drug delivery to the brain.

Methods

Molecular docking (Flare 4.0) followed by dynamic simulations (Material Studio 2022) comprising of LF dG score, Hildebrand solubility parameters (δ), mixing energy, Flory-Huggins parameters (χ), radius of gyration (Rg) and radial distribution function (RDF) were utilized to study binding affinity of various mucoadhesive polymers and RT. Spray-dried NPs were prepared using in silico screened and selected Eudragit RL 100, sodium hyaluronate, or carboxy methyl cellulose and subjected to in vitro characterization.

Results

Significant correlation obtained for in silico predicted values of LF dG, Rg, and RDF, respectively, with experimentally obtained drug loading and particle size of NPs. This unequivocally suggested prognostic role of molecular predictions in dosage form outcome achievement.

Conclusion

High LF dG score, low RDF and Rg values determined through in silico screening suggested, respectively, high yield, encapsulation efficiency, drug loading and small particle size of NPs. Highest ex vivo permeation of RT was observed from Eudragit RL 100 loaded NPs suggesting their promising role for intra nasal delivery.

Purpose

This study aimed to synthesize and characterize silver nanoparticle-embedded layered double hydroxides (Ag-LDH) nanohybrids for potential antimicrobial applications. The research also focused on identifying suitable polymeric hydrogel matrices for embedding the Ag-LDH nanohybrids.

Methods

Ag-LDH nanohybrids were synthesized and the resulting nanohybrids underwent comprehensive characterization using various techniques, including UV-Vis spectroscopy, FTIR spectroscopy, XRD, TGA, DSC, DTA, particle size analysis, zeta potential measurement, and transmission electron microscopy. The antimicrobial activity of the LDH, Ag-NPs, and Ag-LDH was evaluated against a panel of Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and a fungus (Candida albicans) using the agar diffusion method. Polymeric hydrogel matrices, including sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, Carbopol 940, polyvinyl alcohol, and chitosan, were prepared and characterized for their rheological properties using a viscometer.

Results

Characterization techniques confirmed the successful synthesis and intercalation of Ag-NPs within the LDH structure. Antimicrobial studies demonstrated enhanced antibacterial and antifungal activities of the Ag-LDH nanohybrid compared to individual LDH and Ag-NPs. The inhibition zone diameters for Ag-LDH against S. aureus, B. subtilis, E. coli, P. aeruginosa, and C. albicans were 16 ± 0.4 mm, 21 ± 0.8 mm, 16.8 ± 0.7 mm, 19.1 ± 1.1 mm, and 21.3 ± 0.9 mm, respectively. Rheological profiling of the Ag-LDH embedded polymeric matrices revealed varying viscosity profiles, indicating different flow behaviors and potential suitability for various delivery approaches.

Conclusion

The study successfully synthesized, characterized, and demonstrated the enhanced antimicrobial activity of Ag-LDH nanohybrids. Polymeric hydrogel matrices suitable for embedding these nanohybrids were also identified and characterized. Further research, including preclinical studies, could lead to the development of a scalable Ag-LDH hybrid suitable for clinical practice.

Graphical Abstract

Purpose

In this work, we sought to report and fully characterise novel therapeutic deep eutectic systems (THEDESs) formed between Gefitinib (Gef) and capric acid (CA). In addition, we will study the impact of this formulation on solubility and therapeutic efficacy.

Methods

The THEDES were formed using a simple preparation method. Gef and CA were mixed in increasing molar ratios of CA at 40 °C. A phase diagram was used to identify an optimal molar ratio for eutectic formation. Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), and NMR were used to characterise the eutectic systems. Lastly, Cytotoxicity assessments on EGFR-expressing cell lines were conducted to evaluate the therapeutic efficacy of the formulations.

Results

According to the phase diagram, the optimal molar ratio of Gef: CA was found to be G2 (80:20), which facilitates the formation of a homogeneous liquid system at room temperature, confirmed by DSC. FTIR and NMR analysis revealed significant shifts in specific peaks, indicating hydrogen bonding between Gef and CA. More specifically, a downfield shift was observed at protons adjacent to the tertiary nitrogen of the morpholine ring. Gef solubility in CA was enhanced considerably, 30,000 times higher than in aqueous solutions at pH 5. Lastly, according to the cytotoxicity tests, THEDESs, particularly G2 and G3 formulations, have significantly reduced IC50 values compared to individual components, demonstrating a synergistic effect.

Conclusions

The work reports the novel THEDESs of Gef and CA, which enhance Gef solubility and exhibit a synergistic cytotoxic effect against EGFR-expressing cell lines. These findings suggest that THEDESs could offer a promising and facile approach for improving the solubility and therapeutic efficacy of poorly soluble drugs.

Graphical Abstract

Purpose

This study investigates trends in the issuance of FDA warning letters from 2019 to 2023. The paper aims to assess past and present FDA statements of inspection efficiency from a quantitative and qualitative perspective.

Methods

An analytical approach combining regex filtering and web scraping was developed to log citations of law within FDA warning letters. The process included identifying recurring keywords for categorization by keyword, department, and legal reference.

Results

From 2019 to 2023, the FDA went from issuing a warning letter 2.98 times per 100 inspections to 4.27 times per 100 inspections, a 43% increase in warning letters issued per 100 inspections.

Conclusions

From 2019 to 2023, the FDA issued more warning letters more frequently when compared to inspection volume, reallocating resources and priorities throughout the COVID-19 pandemic.

Purpose

Fungal ocular infection is challenging to treat and remains significant cause of blindness globally. The complex structure and physiology of the eye limits the drug targeting to it. Furthermore, post COVID-19 revealed a greater number of patients suffering from fungal eye infection. Hence, current study aimed to develop itraconazole loaded leciplex to enhance the corneal residence time for effective treatment of ocular fungal keratitis infection.

Methods

Itraconazole loaded leciplex were prepared by one-step fabrication process using soy phosphatidyl choline, didodecyl dimethyl ammonium bromide and Transcutol HP. Formulation was optimized via Box-Behnken design. Leciplex were evaluated for particle size, entrapment efficiency, zeta potential, transmission electron microscopy, anti-fungal activity, in vitro release and ex-vivo permeation study through goat cornea, ocular irritation by using hen’s egg test on chorioallantoic membrane (HET-CAM) study and ex-vivo corneal toxicity study.

Results

Itraconazole leciplex exhibited spherical morphology with particle size of 142.5 ± 2.2 nm, entrapment efficiency 99.8 ± 1.8% and zeta potential 62.5mV. In vitro release revealed sustained release pattern of itraconazole leciplex. Further, ex-vivo corneal drug retention study revealed 43.3% retention at the cornea. HET-CAM study and ex-vivo corneal toxicity study confirmed non-irritancy and non-toxicity of leciplex for ocular use. Further, antifungal activity of itraconazole leciplex against Candida albicans demonstrated significantly higher antifungal activity than marketed formulation.

Conclusion

Thus, itraconazole-loaded cationic leciplex delivered itraconazole effectively at corneal surface and adhered at anionic mucosal surface via electrostatic attraction to effectively treat corneal infection fungal keratitis at anatomically challenging regions of the eye.

Objective

Repurposing Eplerenone (EPL) for wound healing through in silico molecular docking to explore its therapeutic potential beyond its traditional use (antihypertensive drug). In this study, for a first time we investigated the potential of EPL- loaded pectin nanoparticles to enhance human skin proliferation.

Methods

Ionotropic gelation method was used for preparing these EPL-loaded PN using calcium chloride as a cross-linker. Design® Expert software was used to utilize a full factorial 2³ design, where the selected factors were the pectin concentration (X₁), EPL amount (X₂), and pectin: calcium chloride concentration (X₃). The selected responses were the EPL entrapment efficiency percentage, particle size and zeta potential for determining the optimum formula for further studies such as in-vitro release studies, transmission electron microscopy (TEM), X-ray diffraction, cell culture study and in-vitro evaluation on human skin fibroblast proliferation cell.

Results

The selected system demonstrated high entrapment efficiency (80.56 ± 0.62%), a particle size of 509.1 ± 45.5 nm, and good zeta potential value (-21.73 ± 2.1 mV). A spherical morphology with no aggregation using TEM and amorphization of the crystalline drug in X-ray diffraction were obtained. The Sulfo-Rhodamine B assay was applied for its effect on cell viability on human skin cells, and the selected concentration was 50 μg/mL.

Conclusions

The wound healing assay on human skin fibroblasts using scratch wound technique showed the superiority of EPL on wound healing; suggesting its promising effect in enhancing skin healing and tissue regeneration. Moreover, pectin activity as a wound healing accelerator, promoting a synergistic effect.

Graphical Abstract

Purpose

Pharmaceutical research continues to focus on developing novel approaches for the effective treatment of ulcerative colitis (UC). To develop a better system than simple nanoparticle-in-microparticle (NP-in-MP), time-dependent NP or MP, and pH-dependent NP or MP, this work sought to construct an enhanced colon-targeting system with a combination of hybrid formulations and dual coating approach consisting of time-dependent nanoparticles loaded in pH-dependent microparticles.

Method

The model drug used was mesalamine, and the polymers used were ethyl cellulose (EC) as time dependent polymer and a mixture of Eudragit L100 (EL100) and Eudragit S100 (ES100) as pH dependent polymer. The NP-in-MP were optimized, prepared and characterized to obtain targeted and sustained delivery of drug. The NP were coated with ethyl cellulose to obtain sustained delivery. Then NP were entrapped within eudragit MP using the double emulsion solvent evaporation process. NP-in-MP were evaluated for particle size, entrapment efficiency, surface morphology, in-vitro drug release and in-vivo evaluation.

Results

The particle size and entrapment efficiency of the selected formulation was 12.4 ± 3.1 µm and 85.36 ± 2.6%. The in vitro drug release profile verified that the selected formulation released (6.94 ± 1.23%) less than 10% of the drug in an acidic environment, followed by continuous drug release (93.9 ± 3.15%) in a colonic environment. The MPO level confirmed that the maximum recovery (i.e., decrease in MPO level) was observed for NP-in-MP (3.02 ± 0.33, ***P < 0.001) followed by NP (6.2 ± 0.51) compared with disease control. NP-in-MP substantially improved body weight, diarrhea score and rectal bleeding (***P < 0.001) which indicates mucosal healing and the mitigation of inflammation. The NP-in-MP significantly increased colon length (***P < 0.001) and reduced spleen weight (**P < 0.01) in comparison to disease control. NP-in-MP also showed improved histological results compared to those of the other treatment groups.

Conclusion

The current findings demonstrate the efficient development of NP-in-MP for enhancing the delivery of NP to the colonic region. The in-vitro data confirms that the NP-in-MP prevented burst release of NP and also targeted them to the colon along with sustained delivery of their payload. The in-vivo data confirms that the NP-in-MP are better in treating colitis than NP. Therefore, it was concluded that a hybrid NP-in-MP can be a potential alternative than other treatment carriers to treat inflammatory bowel disease and colorectal cancer.

Graphical Abstract