Journal of Pharmaceutical Innovation最新文献

Purpose

Methotrexate (MTX) is an antineoplastic drug used in the treatment of rheumatoid arthritis (RA). Given that it is a class IV drug with low permeability and solubility, this study aims to improve MTX skin permeation by loading it in transethosomes (TEs) and casting a transethosomal patch that allows for dose quantification to mitigate toxicity.

Methods

To accomplish this goal, MTX transethosomes (TEs) were developed using the thin film hydration technique and optimized using the Box-Behnken design (BBD) with soya phosphatidylcholine 50, Tween 80, and ethanol as independent variables using the desirability function. Furthermore, zeta potential (ZP) analysis and high-resolution transmission electron microscopy (HR-TEM) were used to confirm the stability and surface morphology of TEs. A transdermal patch was also designed and evaluated from the optimized TE (OPTZ TEs) batch using a solvent casting method with hydroxypropyl methylcellulose (HPMC) as the polymer, dimethyl sulfoxide (DMSO) as a permeation enhancer, and polyethylene glycol (PEG 400) as the plasticizer. Furthermore, ex vivo skin permeation and deposition through rat skin proved that the TE patch had better drug permeation and retention within the skin layers.

Results

The highest desirability batch had 92.19 ± 3.826 nm vesicle size, 0.35 ± 0.062 PDI, 74.05 ± 5.157% EE and 62.75 ± 4.448% Q8h which were within the predicted results. Furthermore, ZP was found to be more than − 30 mV, and HR-TEM results proved that the TE vesicles were spherical. The results of the evaluation parameters such as weight variation, folding endurance, and thickness were 0.07 ± 0.01 g, 82.3 ± 1.52 folds, and 0.93 ± 0.01, respectively, and were well within the limits. The TE patch incorporated more than 90% of the drug confirmed by the drug content analysis which allowed ex vivo permeation for almost 24 h providing a sustained release action with a permeation flux of 19 ± 1.08 and an enhancement ratio of 3.68 when compared to the MTX solution.

Conclusion

This study suggests that MTX-loaded transethosomal patch not only enhanced the skin permeation but also provided a 24-h release profile and reduced its toxicity.

Graphical Abstract

Purpose

The purpose of this study was to investigate the effect of tartaric acid on the maintenance of dipyridamole supersaturation using Eudragit E100 as a carrier.

Methods

The solubility of dipyridamole was determined in a buffer solution (pH = 6.8) containing Eudragit E100 and various concentrations of tartaric acid. Dissolution tests were conducted using a pH-shift method, transitioning from an acidic solution (pH = 1.2) to a buffer solution (pH = 6.8). The drug concentration in the buffer solution was measured to assess drug supersaturation. The dissolution behavior of binary and ternary combinations of dipyridamole, Eudragit E100, and tartaric acid was evaluated and compared. The interference of tartaric acid in the interaction between Eudragit E100 and dipyridamole was assessed using FT-IR and nuclear magnetic resonance (NMR) techniques.

Results

The addition of tartaric acid to Eudragit E100 exhibited a strong synergistic effect in stabilizing the supersaturation of dipyridamole. The results demonstrated that tartaric acid, by lowering the pH, increased the affinity of Eudragit E100 for dipyridamole, thereby enhancing its ability to maintain drug supersaturation.

Conclusion

The presence of acidifiers such as tartaric acid significantly improved the maintenance of drug supersaturation by Eudragit E100 due to the synergistic effect between Eudragit E100 and the acidifier.

Purpose

The purpose of the present work was to develop levofloxacin-flurbiprofen coloaded PLGA (LEV-FLU-PLGA) nanoparticles with surface modification using chitosan to attain mucoadhesion for the treatment of bacterial conjunctivitis.

Method

Polymeric nanoparticles were prepared by nanoprecipitation method and evaluated for parameters like particle size, PDI, zeta potential, entrapment efficiency (%), in vitro drug release, ex vivo permeation studies, microbial assay against Staphylococcus aureus and ocular tolerance using Hen’s egg test-chorioallantoic membrane (HET-CAM). Furthermore, surface of optimized PLGA nanoparticle formulation was modified by coating with chitosan.

Results

LEV-FLU-PLGA nanoparticles demonstrated particle size of 166.1 nm with PDI of 0.137 and zeta potential of − 16.8 mV. The entrapment efficiency was found to be 39.37% for levofloxacin (LEV) and 48.33% for flurbiprofen (FLU), whereas for surface-modified nanoparticles, it was found to be 42.05% for LEV and 45.26% for FLU. LEV-FLU chitosan-coated PLGA nanoparticles showed an increase in particle size, i.e., 333.6 nm with PDI of 0.319 and an inversion of zeta potential to 37.67 mV. The developed nanosystems showed sustained release and improved eye permeability. Microbiological studies showed equivalent zone of inhibition to that of marketed formulation. HET-CAM assay revealed the non-irritant nature of drug-loaded PLGA nanoparticles; however, chitosan-coated PLGA nanoparticles were found to be moderately irritating owing to the acidic nature of formulation.

Conclusion

The nanoparticulate system provides prolonged drug release making it a promising alternative to conventional dosage forms. It reduces systemic effects of locally acting drugs, improving therapeutic efficacy and patient compliance.

Purpose

Continuous wet granulation and drying require an adequate process control strategy to ensure the product quality. The most important critical quality attributes of dried granules are the granule size distribution and moisture content. Process analytical technologies (PATs) are available for real-time monitoring of moisture content by, e.g., near-infrared spectroscopy (NIRS), which requires additional installation and complex multivariate validation. Thus, a mass and energy balance (MEB) was derived for a vibrated fluidised bed dryer, which is part of the QbCon^® 1 intended for continuous wet granulation and drying.

Method

Process parameters that are frequently logged were used for the derivation of a MEB. The predicted MEB was compared with the measured loss-on-drying (LOD) for two different formulations.

Results

The model-derived data were in good agreement with the observed LOD, leading to RMSE values of 0.12–0.45.

Conclusion

The implemented MEB can predict the LOD over time and thus might be suitable as a soft sensor without the installation of additional sensors. The obtained energy flux gives insight into the heat transfer, and the derived energy balance might be used to determine the required energy under certain drying conditions.

Introduction

Topical rapamycin has been established as an effective and safe therapy for facial angiofibromas in tuberous sclerosis. Different formulations have been tested for this skin disease, most using an ointment as a vehicle.

Purpose

To improve the classical formulation of topical rapamycin and to determine the validity period of the proposed options based on chemical, physical, and microbiological stability studies.

Methods

Four different 0.4% rapamycin formulations were prepared (ointment, emulsion, gel, and liposomes). The stability studies for each formulation over 56 days were as follows: (1) chemical: extraction with different solvents and high-performance liquid chromatography assay; (2) physical: pH, uniformity, extensibility, absence of crystals, absence of phase separation, and only for liposomal formulation, particle size, zeta potential, and encapsulation efficiency were determined; and (3) microbiological: culture samples in blood-agar media.

Results

Only liposomes were chemically, physically, and microbiologically stable after 8 weeks. Ointment, emulsion, and gel formulations lost their chemical or physical stability before 56 days.

Conclusions

The authors describe four new formulations to improve the previous treatment for facial angiofibromas in tuberous sclerosis. The liposome-based formulation was the most appropriate according to chemical, physical, and microbiological stability studies. However, it would be necessary to carry out clinical studies to ensure the effectiveness and safety of this formulation and also guarantee an improvement in the quality of life of patients.

Purpose

Psoriasis is a chronic autoimmune inflammatory cutaneous disorder, and single-drug therapy is inadequate for curing this disease. Dual-drug therapy with multi-target synergistic effects may be an alternative approach to eradicate psoriasis. This study reports the development of a lipid-polymer hybrid nanoparticle (LPHNP)-based polymeric hydrogel for topical delivery of methoxsalen (MS) and curcumin (CUR) for the management of psoriasis.

Methods

MS-CUR-LPHNPs were prepared using the emulsification solvent evaporation method and incorporated into a Carbopol-940-based polymeric hydrogel for topical application. The antipsoriatic efficacy of the hydrogel was evaluated in an imiquimod (IMQ)-induced psoriasis rat model.

Results

Methoxsalen-co-loaded curcumin lipid-polymer hybrid nanoparticles (MS-CUR-LPHNPs, 206.8 ± 3.2 nm) were successfully prepared with a narrow polydispersity index (PDI = 0.174), negative zeta potential (− 27.1 ± 6.09 mV), and entrapment efficiency of 84.90 ± 0.68%. The polymeric hydrogel showed all the desirable characteristics essential for topical application. The MS-CUR-LPHNP-based polymeric hydrogel achieved superior anti-psoriatic effects in the IMQ-induced psoriasis rat model because of the high dermal retention of dual drugs for an extended period compared to a standard marketed anti-psoriatic formulation.

Conclusion

Therefore, we concluded that the developed MS-CUR-LPHNPs (D6-HNPs) were novel, providing synergistic therapeutic efficacy and promising prospects for the management of psoriasis.