Nanoparticle engineering is a well-defined technique employed as a novel and effective method in drug design and delivery. It is widely used to control particle size, as well as the morphological and physicochemical properties of active pharmaceutical ingredients. Furthermore, it serves as a method of pre-dispersion preparation for various dosage form developments. Nanotechnology produces nanomaterials with enhanced properties in terms of solubility, dissolution and permeability. In this work, ultrasonic-assisted precipitation was employed to produce nanosuspensions of poorly water-soluble loratadine, using different stabilizers. The objective of our study was attempting to prepare solid nanoparticles of loratadine to be used as a possible intermediate for designing various dosage forms. The effects of the type(s) and concentration(s) of stabilizer(s) on mean particle size were assessed. Optimal process parameters required to produce homogeneous nanoparticles with particle size below 500 nm and polydispersity less than 0.3 were determined both for precipitation and ultrasonication. Pre-dispersions were evaluated for their particle size, polydispersity index and zeta potential. Freeze-drying was employed to produce dry nanoparticles. Particle size, particle size distribution and zeta potential of the dried nanoparticles were measured after reconstitution in water. Besides thermal analysis using DSC and structural analyses (XRPD and FT-IR), the morphological characteristics and dissolution behaviors were also investigated. The selected freeze-dried nanoparticles had a mean particle size range of 353-441 nm, a polydispersity index ranging between 0.167 and 0.229 and a zeta potential between -25.7 and -20.7 mV. These results suggest that material and process parameters were successfully optimized. DSC and XRPD spectra confirmed interactions between the formulation's components during freeze-drying. The solid nanoparticles showed 30-42% of cumulative release after 10 min compared to less than 1% of dissolution characterizing loratadine without pre-processing. This study demonstrates that preparing dried loratadine nanoparticles suitable for designing effective drug preparations is a feasible approach.

Poor bioavailability of ophthalmic drops is mainly due to drainage through the nasal-lacrimal duct and a very low permeability through corneal epithelium. The aim of our study was to prepare and characterize an ocular hydrogel of loratadine, as an example of a lipophilic drug, to increase drug concentration and residence time at the site of action in the eye. In this study, a 23 full factorial design was employed to design and compare the properties of eight different loratadine containing hydrogel formulations. Results showed a significant correlation between the swelling and porosity ratios of the hydrogels and the Pluronic percentage and Pluronic/carbomer ratio in the formulations. Moreover, the release profiles showed fast and sustained release of all the formulations. Evaluation of hydrogels structure by the FT-IR technique indicated that Pluronic interacts with hydroxyl and carboxylic groups in carbomer, which is the main reason of the hydrogel network formation and interacts with loratadine.The permeation of loratadine through rabbit cornea showed that drug permeation percentages for the F2 and F7 formulations were 15 and 70 folds more than that of the control.

This study aims to investigate the effectiveness and safety of Qingfeijianpi therapy for persistent allergic rhinitis (AR).A total of 101 patients with persistent AR were included into the study. These patients were randomly divided into 2 groups: treatment group, in which patients were given Qingfeijianpi decoction (1 dose/day for 4 weeks); control group, in which patients were given an oral dose of loratadine (tablet, 10 mg/time, once per day for 4 weeks). A total of 96 patients completed the 16-week course of treatment. The nasal symptom and traditional Chinese medicine syndrome were scored to evaluate symptom improvement, and the Rhinoconjunctivitis Quality of Life Questionnaire was used to assess the quality of life of patients. Furthermore, the 4-week clinical treatment effect and 16-week follow up were evaluated.After the 4-week treatment, the mean difference in symptom score in the treatment group was similar to that in the control group. However, during the follow-up, the decrease in symptom score was better with the Qingfeijianpi therapy than with loratadine.Compared to loratadine, the Qingfeijianpi decoction exhibited a significant benefit in symptom improvement of persistent AR.

Fast dissolving oral film is a stamp-style, drug-loaded polymer film with rapid disintegration and dissolution. This new kind of drug delivery system requires effective taste masking technology. Suspension intermediate and liposome intermediate were prepared, respectively, for the formulation of two kinds of fast dissolving oral films with the aim of studying the effect of taste masking technology on the bioavailability of oral films. Loratadine was selected as the model drug. The surface pH of the films was close to neutral, avoiding oral mucosal irritation or side effects. The thickness of a 2 cm × 2 cm suspension oral film containing 10 mg of loratadine was 100 μm. Electron microscope analysis showed that liposomes were spherical before and after re-dissolution, and drugs with obvious bitterness could be masked by the encapsulation of liposomes. Dissolution of the two films was superior to that of the commercial tablets. Rat pharmacokinetic experiments showed that the oral bioavailability of the suspension film was significantly higher than that of the commercial tablets, and the relative bioavailability of the suspension film was 175%. Liposomal film produced a certain amount of improvement in bioavailability, but lower than that of the suspension film.

Antihistamines are excreted into breast milk in small amounts; however, there are no adequate published studies or data concerning their effects on newborns and safety during breastfeeding. Thus, the development of sensitive and specific methodologies for the determination of antihistamines in breast milk is critical. A simple and sensitive GC-MS method for the simultaneous determination of 11 antihistamines (diphenhydramine, orphenadrine, chlorpheniramine, dimethindene, meclozine, hydroxyzine, loratadine, desloratadine, cetirizine, rupatadine and ebastine) in breast milk was developed and validated. The antihistamines were solid-phase extracted and derivatized with acetic anhydride and n-propanol. Diazepam-d5 , hydroxyzine-d4 and cetirizine-d8 were used as internal standards. Absolute recovery values for all analytes ranged from 70.5 to 120.0%, while the limits of detection and quantification for all analytes were 1.50 and 5.00 ng/mL, respectively. All calibration curves were linear (R2  ≥ 0.990) within the range 5.00-1000.0 ng/mL. Accuracy (Er ) ranged between -7.6 and 7.0%, while precision (RSD) was <12% for all antihistamines. The developed method is suitable for the investigation of antihistamine-related clinical cases, as well as for pharmacokinetic and breastfeeding safety studies.

Employment of transient expression of foreign genes for bioconversion of pharmaceutically valuable low-molecular-weight compounds, including plant secondary metabolites, is an enticing trend still scantily explored in plant biotechnology. In the present work, an efficient protocol for rapid assessment of synthetic and plant-derived metabolites as potential substrates for human P450s (CYP2D6 and CYP3A4) via Agrobacterium-mediated transient expression in Nicotiana benthamiana is put forth. Animal P450s with broad substrate specificity are promising candidates for transformation of diverse metabolites. The efficiency of P450s in heterologous surroundings is not always satisfactory and depends on the availability of an associated electron-transfer enzyme. Plants represent an attractive assortment of prospective hosts for foreign P450s expression. The optimal composition of genetic blocks providing the highest transient expression efficiency is designed, an effective substrate administration scheme is validated, and biological activity of the investigated P450s against loratadine and several indole alkaloids with different molecular scaffold structures is tested. A novel indole alkaloid, 11-hydroxycorynanthine, is isolated from N. benthamiana plants transiently expressing CYP2D6 and supplemented with corynanthine, and its structure was elucidated. The proposed technique might be of value in realization of combinatorial biosynthesis concept comprising the junction of heterologous enzymes and substrates in different metabolic surroundings.