Pharmaceutical Development and Technology最新文献

The purpose of this study was to investigate the impact of glycyrrhizic acid (GL) concentrations on in vitro and in vivo behavior of quercetin (QT) nanocrystals stabilized by GL (QT-NCs/GL), with a particular focus on its influence on liver targeted drug delivery. QT-NCs/GL with similar particle size around 200 nm were successfully prepared by media milling technique using different concentrations of GL, which were 10%, 20% and 40% (w/w) of the QT. All QT-NCs/GL showed oval and rod shapes, and remained in crystalline state with a reduced crystallinity as GL concentrations increased. All QT-NCs/GL exhibited significant solubility increase and drug release improvement of QT as compared to raw QT. Pharmacokinetics revealed similar plasma concentration-time profiles of QT after intravenous of all QT-NCs/GL. All QT-NCs/GL exhibited rapidly distribution of QT to liver with the maximum QT concentration more than 750 μg/g at 5 min after intravenous administration, and the AUC0∼t of QT for three formulations in liver were significant difference with the following order: QT-NCs/GL-40% > QT-NCs/GL-20% > QT-NCs/GL-10%. These results suggested that different GL concentrations exhibited significant influence on liver targeted delivery of QT-NCs/GL, and more GL used in QT-NCs/GL may contribute more liver distribution of QT.

Metformin is the most common drug used in patients with type 2 diabetes. Our aim is to assess if the in vitro dissolution of Metformin IR 500 mg tablets and its kinetics is altered in the presence of various medication swallowing lubricants used in vivo and to evaluate their rheological properties of tablet lubricant. The dissolution profile of metformin tablets (crushed and whole) mixed with selected medication swallowing lubricants was studied in a Distek^® Dissolution apparatus at 6 different time points (n = 5). Samples were diluted and analysed using a UV-visible Spectrometer at a wavelength of 232 nm using a calibrated absorbance-concentration curve. Dissolution data will be modelled to understand the effect on its dissolution kinetics. Rheology studies were completed using an AR G2 System Rheometer. Gloup^® Forte delayed the in vitro dissolution of metformin from crushed or whole tablets and produced lower peak concentrations, irrespective of the pH of the dissolution media (reduction up to 35% reduction in concentration in pH = 6.8). Gloup^® Forte has changed the release to almost erosion-controlled in different media when mixed with crushed metformin tablets. Further studies evaluating the effects of commonly used thickened fluids on medication may be required to better inform clinical practice.

This study was conducted to develop a lycopene-carrier solid dispersion-loaded lipid liquid crystal nanoparticle (LLC) formulation aimed at enhancing aqueous solubility, bioavailability, and wound healing efficacy. Lycopene was extracted from tomato paste using the Soxhlet method and was formulated into solid dispersions with polyvinylpyrrolidone (PVP) and Poloxamer (Plx) to enhance the solubility of lycopene. The physicochemical properties of the solid dispersion products were characterized. Cytotoxicity on human fibroblast cells, cell migration, and wound healing treatment in the mice were also assessed. PVP demonstrated greater efficacy in enhancing the aqueous solubility of lycopene than Plx. The results indicated that the morphology of the LLC was cubosome, achieving a high encapsulation efficiency of 71.57 ± 2.1%. The LLC formulations demonstrated significantly enhanced release rates of 68.18 ± 1.78% and improved skin permeation compared to the lycopene solid dispersion solution. The results of the cell culture demonstrated the safety of the formulation, and the in vitro scratch test showed the migration of fibroblast cells in the presence of the lycopene-PVP solid dispersion loaded LLC compared to lycopene alone. Based on the obtained results, it can be concluded that the proposed formulation (lycopene-PVP solid dispersion loaded LLC) could be a suitable option for wound healing.

The pandemic caused by the SARS-CoV-2 virus has led scientists to intensify research on antiviral drugs and vaccines. As a result of these studies, it was observed that molnupiravir (MLP) and peramivir (PRV) could be used against pandemic. MLP affects SARS-CoV-2 replication, but it necessitates high doses, which can cause adverse effects in patients. PRV is a neuraminidase inhibitor, but the bioavailability of the drug after oral administration is very low. In this study, MLP-, PRV-loaded and combined liposome (COMB-Lipo) formulations were prepared via the thin film hydration method. Phospholipon 90 G-based formulations exhibited the most favorable characteristics, with a particle size of 111-145 nm, a polydispersity index (PDI) of less than 0.4, and a zeta potential (ZP) of 6-12 mV). Cell culture studies demonstrated that developed stable formulations are nontoxic to L929 and Vero E6 cells. Antiviral activity assessments against SARS-CoV-2 suggested the effectiveness of liposomes in inhibiting viral activity. These findings demonstrate that a possible synergistic effect of the newly developed sustained-release COMB-Lipo formulation is suggested with the complementary antiviral mechanisms of the combined agents. As a result, the therapeutic potential of co-delivery of anti-SARS-CoV-2 drugs for pulmonary application is considered a promising approach for long-acting treatment of COVID-19.

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.