AAPS PharmSciTech最新文献

This study was designed to synthesize quarternized chitosans (Q-CS) and explore their potential application in aqueous solubility enhancement of indomethacin (IND), a BCS class-II drug. Three different Q-CS; N,N,N-trimethyl chitosan chloride (TMC), N-(4-N‘-methylpyridinylmethyl) chitosan chloride (mPyCS), and N-(4-N’,N’,N’-trimethylaminobenzyl) chitosan chloride (TmBzCS) were synthesized and characterized through various spectroscopic analysis. Q-CS-based solid-dispersion (SD) composites of IND (Q-CS-IND) were prepared using the spray-drying method and characterized through Fourier transform infrared (FTIR), scanning electron microscopy (SEM), differential-scanning calorimetry (DSC), and powder X-ray diffraction (P-XRD). The solubility and dissolution profiles of SD-composites of IND were evaluated and compared with physical mixtures (PM). The IND contents were quantified and validated in the composites using UV-Vis spectrophotometer. FTIR and NMR analysis showed the successful preparation of Q-CS. TMC was found with the highest yield (55.13%) and mPyCS with the highest degree of quaternization (DQ) (63.37%). FT-IR analysis of IND-Q-CS composites demonstrated chemical interaction between carbonyl moieties of IND with functional groups of Q-CS. DSC and PXRD analyses demonstrated the transformation of IND in SD composites from crystalline to an amorphous form. All the IND-Q-CS composites were observed with a significant increase in the solubility and dissolution rate of the drug (1996.0 µg/min) compared to PM (1306.8 µg/min), which is higher than pure IND (791.6 µg/min). The contents of IND in TMC, mPyCS, and TmBzCS composites were 97.69–99.92%, 97.66-100.25%, and 97.18-100.11% respectively. Overall, the findings encourage the applications of Q-CS derivatives for increasing IND water solubility and warrant further in vivo biological profiling of IND composites.

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In recent years, there has been a significant increase in the prevalence of thyroid diseases, particularly hypothyroidism. In this study, we investigated the impact and mechanisms of Chemical permeation enhancement(CPE) on transdermal permeation of levothyroxine sodium (L-T4) patches.We found that the combination of oleic acid (OA) and Azone (NZ) yielded the best transdermal permeation effect for L-T4.Subsequently, we also investigated the relevant propermeability mechanism.The results demonstrate that the combined application of OA and NZ significantly enhances the transdermal permeation of L-T4 compared to individual applications,it is attributed to two mechanisms: firstly, OA improves drug release by increasing the flowability of the pressure-sensitive adhesive (PSA) matrix; secondly, both OA and NZ act on the stratum corneum, especially facilitating L-T4 permeation through the hair follicle pathway. No skin irritation or cytotoxicity is observed with these final patches, which exhibit a remarkable therapeutic effect on hypothyroidism. this study contributes to the development of transdermal formulations of L-T4.

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Dry powder inhalers (DPIs) are state-of-the-art pulmonary drug delivery systems. This article explores the transformative impact of nanotechnology on DPIs, emphasizing the Quality Target Product Profile (QTPP) with a focus on aerodynamic performance and particle characteristics. It navigates global regulatory frameworks, underscoring the need for safety and efficacy standards. Additionally, it highlights the emerging field of nanoparticulate dry powder inhalers, showcasing their potential to enhance targeted drug delivery in respiratory medicine. This concise overview is a valuable resource for researchers, physicians, and pharmaceutical developers, providing insights into the development and commercialization of advanced inhalation systems.

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Purpose

Twin-screw wet granulation (TSWG) is a manufacturing process that offers several advantages for the processing of water-insoluble active pharmaceutical ingredients (APIs) and has been used for increasing the solubility and dissolution rates. Here we introduce a novel TSWG approach with reduced downstream processing steps by using non-volatile solvents as granulating binders.

Methods

Herein, TSWG was carried out using Transcutol a non-volatile protic solvent as a granulating binder and dissolution enhancer of ibuprofen (IBU) blends with cellulose polymer grades (Pharmacoat^® 603, Affinisol™, and AQOAT^®).

Results

The physicochemical characterisation of the produced granules showed excellent powder flow and the complete transformation of IBU into the amorphous state. Dissolution studies presented immediate release rates for all IBU formulations due to the high drug-polymer miscibility and the Transcutol solubilising capacity.

Conclusions

Overall, the study demonstrated an innovative approach for the development of extruded granules by processing water-insoluble APIs with non-volatile solvents for enhanced dissolution rates at high drug loadings.

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The current study aimed to evaluate the efficacy of orally administered rapid mini-tablets containing atomoxetine hydrochloride (ODMT) relative to the conventional capsule formulation of atomoxetine hydrochloride (ATO). To mask the bitter taste of ATO and render it more palatable for pediatric administration in individuals with Attention Deficit Hyperactivity Disorder (ADHD), an inclusion complex of ATO with β-cyclodextrin (β-CD) was synthesized. The ODMT and conventional capsule ATO formulations were administered orally to a cohort of ADHD rat pups born to nicotine-exposed dams, facilitating an in vivo efficacy assessment. Behavioral assays, including the open field test, novel object recognition test, and Barnes maze test, were conducted pre- and post-administration of the therapeutics. The outcomes suggested that the ODMT formulation, incorporating ATO-β-CD inclusion complexes, shows promise as a viable alternative to the capsule form of ATO. Conclusively, the preparation of the ATO-β-CD complexes and ODMTs leveraged a factorial experimental design, with the animal model being subjected to nicotine-induced hyperactivity to provide a unique evaluative framework for the ODMT formulation under development.

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Acne affects most of the world's population, causing an impact on the self-esteem of adolescents and young adults. One of the causes is the presence of the bacteria Cutibacterium acnes which are part of the natural microbiota of the skin. Topical treatments consist of anti-inflammatory and antibiotics, which could select resistant strains. Alternatives to the antibiotic are biocomposites that have antimicrobial activity like biosurfactants which are produced by bacteria. An innovative way of applying these compounds is bioadhesive polymeric films that adhere to the skin and release the active principle topically. Rhamnolipids have great potential to be used in the treatment of acne because they present antimicrobial activity against C. acnes in low and safe concentrations (MIC of 15.62 µg/mL, CBM of 31.25 µg/mL and CC50 of 181.93 µg/mL). Four films with different rhamnolipids concentrations (0.0; 0.1; 0.2; and 0.3%, w/w) were obtained as to visual appearance, mass variation, thickness, density, solubility, pH, water vapor transmission, mechanical properties (folding endurance, bioadhesion strength, tensile strength, elongation at break and Young's modulus), scanning electron microscopy and infrared. The results show that these formulations had a homogeneous appearance; elastic mechanical properties; pH similar to human skin and bioadhesive. The polymeric films containing rhamnolipids were effective against C. acnes, in the in vitro test, at the three concentrations tested, the film with the highest concentration (0.3%, w/w) being the most promising for presenting the highest antimicrobial activity. Thus, the polymeric film containing rhamnolipids has the potential to be used in the treatment of acne.

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The objective of this study was to create a new treatment for lung cancer using solid lipid nanoparticles (SLNs) loaded with gemcitabine (GEM) and epigallocatechin-3-gallate (EGCG) that can be administered through the nose. We analyzed the formulation for its effectiveness in terms of micromeritics, drug release, and anti-cancer activity in the benzopyrene-induced Swiss albino mice lung cancer model. We also assessed the pharmacokinetics, biodistribution, biocompatibility, and hemocompatibility of GEM-EGCG SLNs. The GEM-EGCG SLNs had an average particle size of 93.54 ± 11.02 nm, a polydispersity index of 0.146 ± 0.05, and a zeta potential of -34.7 ± 0.4 mV. The entrapment efficiency of GEM and EGCG was 93.39 ± 4.2% and 89.49 ± 5.1%, respectively, with a sustained release profile for both drugs. GEM-EGCG SLNs had better pharmacokinetics than other treatments, and a high drug targeting index value of 17.605 for GEM and 2.118 for EGCG, indicating their effectiveness in targeting the lungs. Blank SLNs showed no pathological lesions in the liver, kidney, and nasal region validating the safety of SLNs. GEM-EGCG SLNs also showed fewer pathological lesions than other treatments and a lower hemolysis rate of 1.62 ± 0.10%. These results suggest that GEM-EGCG SLNs could effectively treat lung cancer.

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Immunotherapy is one of the most promising therapeutic approaches in the field of cancer treatment. As a tumor progresses, tumor cells employ an array of immune-regulatory mechanisms to suppress immune responses within the tumor microenvironment. Using our understanding of these mechanisms, cancer immunotherapy has been developed to enhance the immune system’s effectiveness in treating cancer. Numerous cancer immunotherapies are currently in clinical use, yet many others are either in different stages of development or undergoing clinical studies. In this paper, we briefly discuss the features and current status of cancer immunotherapies. This includes the application of monoclonal antibodies, immune checkpoint inhibitors, adoptive cell therapy, cytokine therapy, cancer vaccines, and gene therapy, all of which have gained significant recognition in clinical practice. Additionally, we discuss limitations that may hinder successful clinical utilization and promising strategies, such as combining immunotherapy with nanotechnology.

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The goal of the present study was to prepare meloxicam (MX) entrapped hybrid particles (HPs) to enhance intestinal permeation and anti-inflammatory activity. MX-HPs were prepared by nanoprecipitation method using lipid, chitosan, poloxamer, and TPGS. The formulations (MX-HPs1, MX-HPs2, MX-HPs3) were evaluated for particle size, entrapment efficiency, and drug release to select the optimized composition and further evaluated for permeation study, stability study, morphology, interaction study, and anti-inflammatory activity by carrageenan-induced rat paw edema test. The prepared MX-HPs showed nano sized particles (198.5 ± 3.7 to 223.8 ± 2.1 nm) and PDI (<0.3), zeta potential (16.5 ± 2.7 to 29.1 ± 3.6 mV), and high entrapment efficiency (75.1 ± 4.7 to 88.5 ± 3.9%). The surface morphology was assessed by transmission electron microscopy and showed non-aggregated particles. Infra-red (IR) spectroscopy of pure MX as well as formulation revealed no drug-polymer interaction and X-ray diffraction confirmed the conversion of crystalline MX into amorphous form. The release study data revealed prolonged MX release for 24 h. The selected optimized hybrid particles (MX-HPs2) revealed a 2.3-fold improved enhancement ratio than free MX. The storage stability and gastrointestinal stability data demonstrated a stable formulation in SIF as well as SGF. The anti-inflammatory activity showed better therapeutic action than pure MX dispersion. From the study, it can be concluded that the prepared MX-HPs may be a promising delivery system for MX in treating inflammatory disorders.

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