Journal of Pharmaceutical Innovation最新文献

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.

Purpose

Many current drug delivery technologies are ineffective and require high concentrations of active drugs for effective therapy. Novel drug delivery systems (NDDS) are increasingly being investigated to achieve targeted and controlled drug release. This study uses a microsponge-loaded drug delivery system to overcome the problem associated with traditional therapy for diaper dermatitis. Therefore, we aimed to formulate and characterize luliconazole microsponge-loaded gel for anti-fungal activity.

Methods

Quasi-emulsion solvent diffusion method was used for developing luliconazole microsponge. The characterization of drug-loaded microsponge was investigated. Optimization of formulation carried out through in vitro release studies and entrapment efficacy. The formulation of microsponge-loaded gel was carried out and evaluated using physicochemical studies. The effectiveness of optimized formulations was examined for anti-fungal activity against Candida albicans.

Results

The prepared microsponge was found to have a particle size between 20 and 50 µm, an entrapment efficiency of 53 ± 0.3–92.7 ± 0.1% and a drug release of 71.8 ± 0.2–88.5 ± 0.02%. The pH was in the range of 6.8–7.4, and the viscosity of the prepared formulation was 265.5 cPs. In vitro, the release of luliconazole microsponge-loaded gel showed that formulation F6 has the highest percentage (%) of cumulative drug release (CDR) compared to other formulations. The anti-fungal activity of the microsponge-loaded gel against Candida albicans showed a clear zone of inhibition in the F6 formulation.

Conclusion

Our study results demonstrate that the F6 formulation has the highest % of CDR and shows better anti-fungal activity. Therefore, luliconazole microsponge-loaded gel formulation can improve drug delivery in diaper rash caused by fungal infection.

Graphical Abstract

Purpose

Skin fungal infections are widely spreading worldwide and are considered a main cause of skin, mucous membranes, and systemic diseases. In an approach to enhance the topical delivery of miconazole nitrate (MZN) as a poorly permeable antifungal agent, spanlastics nanocarriers as a type of elastic vesicles were adopted in the current work.

Methods

MZN spanlastics were prepared and optimized according to a D-optimal response surface design to investigate the influence of formulation variables, edge activator (EA) percentage, EA type on particle size (PS), and drug entrapment efficiency percentage (% EE) as dependent variables. The spanlastics optimized formula (F7) was further assessed for its elasticity and physico-pharmaceutical properties before being incorporated into a gel. The F7 gel formula was also examined for its physical properties, in vitro release, in vitro antifungal activity against Candida albicans (ATCC® 10231), and ex vivo skin deposition studies. The results of the F7 gel formula were compared to the F7 aqueous dispersion.

Results

The D-optimal design revealed that F7, developed using Tween 60 as EA and Span 60 at a weight ratio 2:8, is the optimized formula. F7 was an elastic, spherical, non-aggregated vesicle with an average PS of 210 nm and a drug entrapment efficiency of 90%. The drug was present in an amorphous form within the vesicles. The gel form of F7 showed a prolonged drug release behavior relative to the solution form, where 75% of the drug was released over 10 h for the former and 5 h for the latter. The antifungal study revealed a significant (p < 0.05) increase in the zone of inhibition of Candida albicans (ATCC® 10231) demonstrated by spanlastics compared to MZN suspension at the same concentration level. MZN suspension showed cytotoxic activity at a concentration of 20 μg/mL and above; the incorporation of the drug in spanlastics dispersion or gel form increased the cell viability percentage. The skin deposition studies showed that F7 deposition in the dermal layer, where deep skin infections occur, is 164-folds that of the plain drug.

Conclusions

The results confirm the potential application of MZN-spanlastics to treat deeply seated skin fungal infections.

Purpose

Dynamic carrier-free theranostic nanodrugs are in great demand, owing to their extraordinary high drug loading, enhanced targeting therapy, and panoramic tracking of the drug behaviors. Herein, this work highlights a successful development of pH-triggered dynamic carrier-free nanodrugs for precise tumoral targeting theragnostic, which are established through self-assembly between dasatinib (DAS) and chlorambucil (CLB).

Methods

The study has proved the structure, change in particle size and zeta potential, fluorescence transition, cellular uptake, cytotoxicity as well as biosafety of the carrier-free nanodrugs. The nanodrugs are characterized by Fourier transform infrared spectroscopy, ¹H nuclear magnetic resonance, X-ray diffraction, Dynamic light scattering, and Microplate reader. Cellular uptake and cytotoxicity assay are conducted for free drugs and their nanodrugs using tumor cell lines including A549, HepG2, K562, and THP1. ICR mice are applied to evaluate the biosafety of nanodrugs.

Results

The introduction of CLB into DAS nanoparticles can successfully redshift the emission wavelength from 420 to 810 nm. Moreover, the nanodrugs exhibit a dynamic fluorescence intensity conversion via tumoral intracellular gradual quenching of Aggregation-induced emission (AIE). This characteristic is beneficial to the precise monitoring of tumoral intracellular drug behaviors. Furthermore, the nanodrugs show a small-to-large size transition from 175 nm to more than 500 nm in 12 h and surficial charge reversal from −2.3 mV to more than 0.2 mV by protonation at tumoral pHs. These superior properties facilitate the improved cellular uptake and synergistic cytotoxicity on various types of tumor cells.

Conclusion

The study shows that nanodrugs made of DAS and CLB that can self-assemble without carriers under different pH levels may be ready for testing in tumor targeting, and might someday be helpful for diagnosis and treatment in the future.