Pharmaceutical Development and Technology最新文献

Levodopa (L-dopa) an effective treatment for Parkinson's disease, but it exhibits low oral bioavailability. Intranasal L-dopa nanosuspensions were manufactured to improve bioavailability using the olfactory and trigeminal delivery routes for direct brain delivery. The development of L-dopa nanocrystals and in vitro characterization was undertaken. Nanosuspensions were optimized using Design of Experiments. The L-dopa nanosuspension was produced at 50 °C using sonoprecipitation and mechanical stirring. Water and ethanol were solvent and antisolvent, and Tween^® 80 and cetyltrimethylammonium bromide, stabilizing agents. The critical quality attributes (CQA) monitored were droplet size (PS), polydispersity index (PDI), Zeta potential (ZP), and percent yield (%), pH and osmolarity of the optimized formulation were monitored. SEM, pXRD, DSC, FTIR, and in vitro release were used for further characterization. Short-term stability testing at 4 °C and 22 °C was evaluated for 28 days. The mean PS, PDI, ZP, and % yield of the optimized nanosuspension were 161.4 ± 20.152 nm, 0.383 ± 0.090, +15.45 ± 1.664 mV, and 72.106 ± 0.023%, respectively. In vitro test results for the optimized formulation show the target CQA, had been met. The system may enhance the bioavailability of L-dopa when administered intranasally. In vivo studies are required to confirm nose-to-brain transport.

The goal of our study is to augment ticagrelor (TC)'s dissolution rate and antiplatelet activity via controlled antisolvent precipitation. A saturated ethanolic solution of TC was prepared in the absence and presence of poloxamer 188 or gelucire 44/14. Aerosil 200 was added before controlled precipitation using water or water-containing poloxamer (1% w/v). The resulting precipitate was dried and characterized using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and in vitro dissolution. FTIR showed hydrogen bonding after the processing of TC. DSC and PXRD reflected partial amorphization. A significant enhancement (p < 0.05) in dissolution efficiency and TC amount released after five minutes was also shown. The most effective composition was F6, which comprised TC, poloxamer, and Aerosil (5:5:2.5), or F9, utilizing gelucire instead of poloxamer at a similar ratio. Assessment of tail bleeding time (min) exhibited a significant (p < 0.05) prolongation for rat groups treated with F6 (24.71 ± 5.46) and F9 (30.06 ± 1.63) compared with negative control (3.43 ± 0.46) and unprocessed TC (5.78 ± 2.18). These results suggest an enhancement of TC's pharmacological activity probably due to enhanced bioavailability imparted with an enhanced dissolution rate. The study introduced controlled antisolvent precipitation as a simple tool for hastened TC's dissolution.

This study investigated incorporating Terbinafine Hydrochloride (TH) into chitosan-coated nanostructured lipid carrier (NLCs) to improve ocular treatment for fungal keratitis. Solubility studies were conducted to determine the most suitable lipids for NLCs formulation. TH-loaded NLCs were prepared via emulsification followed by ultrasonication. The impact of various lipids and surfactants on the formulation was investigated. The optimal formulation (TH-NLC10) was coated with chitosan (0.5% w/v), resulting in the coated TH-NLC10-CS 0.05% formulation. This formulation was evaluated for physicochemical properties, morphology, in-vitro release, mucoadhesion, permeation, and in vivo efficacy in treating ocular fungal keratitis in rabbits. Results revealed variations in lipids and surfactants significantly affected particle size. All prepared TH-NLCs formulations within the nanometer range. Physicochemical characterizations of the coated TH-NLC10-CS 0.05% showed 88.37 ± 2.41 nm size, 20.2 ± 1.4 mV zeta potential, 93.3 ± 1.5% w/w entrapment efficiency, and spherical morphology. TH-NLC10-CS 0.05% exhibited sustained TH release (66.65 ± 4.3% over 8 h) and strong mucoadhesion as indicated by a decrease in zeta potential from +20.2 ± 1.4 mV to +2.9 ± 0.7 mV. TH-NLC10-CS 0.05% demonstrated a 2.4-fold increase in TH permeation compared to plain TH, along with effective in vivo antifungal activity. This study confirms that mucoadhesive NLCs with TH are promising for the treatment of ocular fungal keratitis.

The COVID-19 pandemic exposed the fragility of today's marketed treatments for respiratory infections. As a primary site of infection, the upper airways may represent a key access route for the control and treatment for these conditions. The present study aims to explore and identify, through a patent review, the novelty of therapies for COVID-19 that use the intranasal route for drug administration. A search was carried out in Wipo and Espacenet, using the descriptors 'COVID-19 OR SARS-CoV 2' AND 'treatment OR therapy' AND NOT 'vaccine OR immunizing' and the classification 'A61K9/0043'. Of the 151 patents identified, we excluded 73 duplicates, and 36 documents that meet the criteria adopted for exclusion (not nasally administered formulations, vaccines, post COVID-19 treatments, uncertain route of administration or form). We identified 78 unique patents on patent databases, of which 42 were selected for this review. The documents revealed the use of the intranasal pathway not only for drug repositioning but also for using plant-derived and biological molecules. Overall, the new formulations explore a variety of known drugs and natural products incorporated in drug carrier systems and devices for drug delivery and administration. Thus, the intranasal route remains a promising strategy for drug delivery, offering direct access to the primary infection site and warranting further exploration.

Self nano-emulsifying drug delivery system (SNEDDS) has been widely used to enhance dissolution and bioavailability of glibenclamide (GB). In addition, black seed oil, containing bioactive thymoquinone (TQ), showed promising antihyperglycemic effect. Therefore, this work aims to design solid SNEDDS formulation loaded with Black seed oil and GB. SNEDDS formulations were prepared and characterized for miscibility, dispersibility, droplet size, zeta potential, and in-vitro dissolution. Moreover, antidiabetic activity of prepared formulation against pure drug was evaluated using streptozotocin-induced diabetic rat model. The selected liquid SNEDDS (F7) formulation consisted of Kolliphor EL: Caproyl 90: BSO that produced nanoemulsion particles (24.9 ± 0.2 nm). Different solidified formulations were prepared from F7, and the solidified (S4) formulation was selected as optimum formulation that showed GB and TQ had a DE% value of 73.16 ± 0.59 and 70.9%, respectively. Overall, both pure GB and GB-SNEDDS formulations significantly reduced blood glucose levels compared to the control diabetic group. The GB-SNEDDS showing superior efficacy (67% reduction, p = 5.5 × 10^-5) compared to pure GB (52% reduction, p = 1.5 × 10^-4). Moreover, the GB-SNEDDS formulation has a significant (p = 0.0363) reducing action on blood glucose levels compared with the pure GB group. Present results showed that the prepared formulation boosted the antidiabetic activity of GB.

Pyrazinamide (PYZ), a nicotinamide derivative, is an essential first-line anti-TB drug. However, its dose-dependent hepatotoxicity poses a considerable challenge, accentuating the need for improved delivery approaches. The key objective of the research work was to develop mannose-appended pyrazinamide-containing solid-lipid nanoparticles (Mn-PYZ-SNs) for the targeted management of TB. The developed Mn-PYZ-SNs depicted a particle size of 422±09 nm, which was slightly higher than that of unconjugated PYZ-SNs (Un-PYZ-SNs)(401±08 nm), with a minimal reduction in entrapment efficiency(83.64±1.42%). The in vitro drug release studies demonstrated comparable sustained release patterns for both formulations, with a similarity factor (f2) of 77.33, indicating that the structural integrity of PYZ-SNs was maintained during mannose conjugation. Fluorescence imaging and flow cytometric analysis revealed significantly enhanced cellular uptake of Mn-C6-SNs, with a 1.60-fold increase compared to Un-C6-SNs. The in vivo pharmacokinetic studies conducted on Sprague-Dawley rats showed a 4.7-fold improvement in relative bioavailability for Mn-PYZ-SNs. Biodistribution studies demonstrated significantly higher lung accumulation of Mn-PYZ-SNs (1.93-fold) compared to Un-PYZ-SNs at 24 hours. The aforementioned results imply that the developed Mn-PYZ-SNs could be a promising carrier for the treatment of TB. via the oral intestinal lymphatic pathway, circumventing its hepatic first-pass metabolism, and thereby preventing hepatic adverse effects.

Liver cancer is common worldwide and associated with relatively high mortality. Sorafenib is a first-line treatment for advanced liver cancer, but its efficacy is limited by its high toxicity, wide distribution in the body and low water solubility. Combination therapy with multiple drugs can lead to greater therapeutic efficacy, and nano-delivery systems can facilitate such therapy by solubilizing drugs and thereby increasing their bioavailability. Here nanoparticles of sorafenib and emodin encapsulated in the copolymer PEG-PLGA were constructed for liver therapy. Nanoparticles carrying sorafenib and emodin were prepared using a double emulsion method, and showed a diameter around 290 nm and uniform morphology. The encapsulation rates of sorafenib and emodin were 77.4 ± 0.71% and 80.78 ± 0.05%, the drug loading rates were 12.0 ± 0.1% and 13.0 ± 0.21%, and the cumulative drug release rates in pH 5.0 medium were 83.6% and 80.2%. The dual-loaded nanoparticles demonstrated significantly suppressed cellular proliferation and markedly enhanced apoptotic induction compared to free drug formulations or monotherapy nanoparticles. In murine xenograft models, the nanoparticles achieved superior tumor growth suppression (p < 0.01 vs free drugs). These findings collectively indicate that the sorafenib-emodin co-encapsulated PEG-PLGA nanoparticles represent a promising therapeutic platform for hepatocellular carcinoma intervention and may provide more therapeutic options against advanced liver cancer.

Thymus capitatus (Th. Ca) is known to treat mouth ulcers and respiratory infections in Cyprus. However, antioxidant, antibacterial, and cytotoxic potential of Th. Ca. EO on MDA-MB-231 cells and its' encapsulation into nanoparticles has not been well studied. Therefore, we aimed to analyze the antioxidant, antibacterial, cytotoxic potential, loading efficiency, and in vitro release profile of both Th. Ca. EO and Chitosan Nanoparticle (Ch. Np) - Th. Ca. EO. GC-MS analysis revealed 53.97% carvacrol, 14.53% borneol, and 12.09% sabinene presence in EO. The loading efficiency of Th. Ca. EO into Ch. Np. was calculated as 35.27% and the in vitro release profile reached a maximum of 68% in pH 7 for two weeks. The Minimum Inhibitory Concentration (MIC) assay showed that E. coli had an MIC₅₀ of 0.3215 mg/ml while B. subtilis had an MIC₅₀ of 0.5304 mg/ml. The antioxidant activity of the EO was assessed by performing a DPPH assay with an IC₅₀ = 440 μg/ml. Trypan Blue Assay revealed that 60 µg/ml Th. Ca. EO significantly reduced the cell viability of MDA-MB-231 cells by 10.7% at 48h and 20.06% at 72h. Overall, Ch. Np. - Th. Ca. EO has shown a promising formulation for the pharmaceutical industry.

Fungal infections are among the common diseases affecting the skin, which necessitate either topical or systemic delivery of antifungal agents. Eugenol was reported to exhibit antifungal properties, but owing to its poor skin-penetration ability, it requires encapsulation within delivery carriers. This study aimed to enhance the skin penetration and antifungal efficacy of eugenol through encapsulation in novel aspasomal formulations. Cationic and anionic aspasomes were prepared using ascorbyl palmitate, transcutol, and charge inducers, achieving high encapsulation efficiencies (90.55% for cationic, 63.32% for anionic) and stable formulations. Ex-vivo skin deposition studies showed significant eugenol retention in deeper skin layers, with 82.2% (cationic) and 77.2% (anionic) total skin deposition. Both formulations demonstrated superior antifungal activity compared to eugenol solution, with larger zones of inhibition against Candida albicans and Trichophyton rubrum. Clinical trials in patients with candidiasis and dermatophytosis revealed complete resolution of symptoms in 100% of patients treated with aspasomes, while eugenol solution showed partial improvement. These findings suggest that aspasomal encapsulation significantly enhances eugenol's therapeutic potential, offering a promising strategy for improving the treatment of fungal skin infections.

Polymeric films are promising formulations for oromucosal drug delivery, particularly for localized treatment of dental diseases. This study focused on developing mucoadhesive films for dental applications, incorporating clove CO₂ extract and essential oils of lavender and grapefruit as active ingredients. The films were prepared using the solvent casting method, with various film-forming agents (sodium alginate, sodium carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol) used individually and in combinations, without or with plasticizers (glycerol, polyethylene glycol 400, or their mixtures). To optimize the selection of mucoadhesive polymer and plasticizer, properties such as appearance, thickness, pH, moisture content, bursting strength, tensile capacity, elasticity, dissolution, and adhesion, were evaluated. The combination of hydroxyethyl cellulose and hydroxypropyl cellulose with polyethylene glycol 400 was proved most suitable, ensuring superior organoleptic, physicochemical, and textural characteristics. The films demonstrated strong mucoadhesion (9.20 ± 0.58 N), contributing prolonged retention on the mucosa and enhanced bioavailability of the active ingredients. In vitro release studies showed sustained release profile, with approximately 90% of eugenol released during the final film dissolution phase (360-420 min), supporting prolonged therapeutic effects and enhanced local therapy efficacy. The films also exhibited significant antimicrobial activity against a broad spectrum of microorganisms, confirming their potential for treating infectious and inflammatory oral diseases.