Preparation of Poly-Lactic-Co-Glycolic Acid Nanoparticles in a Dry Powder Formulation for Pulmonary Antigen Delivery

One of the key requirements for successful vaccination via the mucosa is particulate antigen uptake. Poly-lactic-co-glycolic acid (PLGA) particles were chosen as well-known model carriers and ovalbumin (OVA) as the model antigen. Aiming at application to the respiratory tract, which allows direct interaction of the formulation with the mucosal immune system, this work focuses on the feasibility of delivering the antigen in a nanoparticulate carrier within a powder capable of pulmonary delivery. Further requirements were adequate antigen encapsulation in order to use the characteristics of the particulate carrier for (tunable) antigen release, and capability of the production process for industrialisation (realisation in industry). For an effective particulate antigen uptake, nanoparticles with a size of around 300 nm were prepared. For this, two production methods for nanoparticles, solvent change precipitation and the double emulsion method, were evaluated with respect to antigen incorporation, transfer to a dry powder formulation, redispersion and antigen release characteristics. A spray drying step was included in the production procedure in order to obtain a respirable powder with an aerodynamic particle size of between 0.5 and 5 μm. The dried products were characterised for particle size, dispersibility and aerodynamic behaviour, as well as for immune response and cytotoxicity in cell culture models. It could be shown that the double emulsion method is suitable to prepare nanoparticles (270 nm) and to incorporate the antigen. By modifying the production method to prepare porous particles, it was possible to obtain an acceptable antigen release while maintaining an antigen load of about 10%. By the choice of polyvinyl alcohol as a stabiliser, nanoparticles could be dried and redispersed without further excipients and the production steps were capable of realisation in industry. Aerodynamic characteristics were good with a mass median aerodynamic diameter of 3.3 µm upon dispersion from a capsule-based inhaler.

Mathematical planning of experiments to optimize the extraction of extractive substances from needles of Pinus sylvestris

Представленная работа посвящена определению оптимальных условий выделения суммы экстрактивных веществ из древесной зелени сосны методом эмульсионной экстракции. Экологически безопасный эмульсионный метод экстракции растительного сырья в водно-щелочной среде не уступает традиционным методам извлечения низкомолекулярных компонентов и позволяет эффективно выделять как гидрофильные, так и гидрофобные соединения. Объектом данного исследования являются отходы лесозаготовок - древесная зелень сосны обыкновенной - источник природных биологически активных веществ, имеющих практическое применение. Определение оптимальных условий экстракции ДЗ сосны эмульсионным способом в данном исследовании было проведено методом поверхности отклика с использованием ротатабельного композиционного униформ-плана второго порядка, который включал 13 экспериментальных опытов со всеми возможными комбинациями уровней двух изучаемых факторов: концентрации водного раствора NaOH и гидромодуля : отношения объема щелочного раствора к массе сырья. Анализ результатов исследований показал, что в заданном интервале варьирования факторов наибольшее влияние на выход экстрактивных веществ оказывает гидромодуль, при увеличении которого до 10:1 выход увеличивается, далее устанавливается равновесная концентрация в системе «сырье – экстрагент». Установлены оптимальные условия эмульсионной экстракции древесной зелени сосны: концентрация водного раствора NaOH - 5%, гидромодуль - 10:1. В оптимальных условиях выход экстрактивных веществ составил 9,84% от массы сухого сырья, что сопоставимо с результатами, полученными традиционными методами экстракции сырья органическими растворителями. The presented work is devoted to the determination of the optimal conditions for the isolation of the sum of extractives from wood greenery (WG) of Pinus sylvestris by the method of emulsion extraction. The environmentally friendly emulsion method for the extraction of plant raw materials in an aqueous-alkaline medium is not inferior to the traditional methods of extracting low molecular weight components and makes it possible to effectively isolate both hydrophilic and hydrophobic compounds. The object of this study is logging waste – woody greenery of Pinus sylvestris – a source of natural biologically active substances that have practical application. The determination of the optimal conditions for the extraction of WG pine by the emulsion method in this study was carried out by the response surface method using a rotatable compositional uniform plan of the second order, which included 13 experiments with all possible combinations of the levels of two studied factors: the concentration of an aqueous solution of NaOH and the hydromodule – ratio of the volume of water-alkaline solution to the mass of raw materials. Analysis of the research results showed that in a given range of variation of factors, the greatest influence on the yield of extractive substances is exerted by the hydromodule, with an increase of which to 10: 1, the yield increases, then an equilibrium concentration is established in the "raw material – extractant" system. The optimal conditions for emulsion extraction of WG pine were established: concentration of an aqueous solution of NaOH – 5%, hydromodule 10:1. Under optimal conditions, the yield of extractive substances was 9,84% of the weight of the dry raw material, which is comparable with the results obtained by traditional methods of raw material extraction with organic solvents.

Quality by design prospects of pharmaceuticals application of double emulsion method for PLGA loaded nanoparticles

QbD approach empowers the pharma researchers to minimize the number of experimental trials and time. It helps identify the significant, influential factors such as critical material attributes, critical formulation variables, and critical process parameters, which may significantly impact the quality of the products. Poly lactic-co-glycolic acid (PLGA), a biocompatible and biodegradable polymer, has gained an immense potential and wide range of applications as a carrier for manufacturing of polymeric nanoparticle drug delivery systems as per US-FDA and European Medicine Agency for drug delivery. The double emulsion method for preparing PLGA nanoparticles to encapsulate hydrophilic drugs has attracted interest in manufacturing processes. The double emulsion is a two-step process consisting of two different emulsification, making the process more complicated. The stability of nanoparticles obtained by a double emulsion method remains questionable due to the many formulations and process attributes. Currently, PLGA based nanoparticles prepared by a double emulsion technique are an alternative pharmaceutical manufacturing operation for getting the quality product by employing the Quality by Design approach. This present review has discussed the QbD elements to elucidate the effect of material attributes, formulation, and process variables on the critical quality attributes of the drug product, such as particle size distribution, encapsulation efficiency, etc. The components of a double emulsion, characteristics of drugs, polymers, and stabilizers used have been discussed in detail in this review. Graphic abstract

Lidocaine Hydrochloride Nanoparticles Preparation using Multiple Emulsions and its Physicochemical Evaluation

Lidocaine is a primary local anesthesia that blocks the ionic fluxes required for the beginning and operation of impulses in the neuronal membrane. The benefits of local anesthetics, such as enhancing patient acceptance, prohibiting systemic toxicity and delivering continuous drug delivery, make them the attracting field for pharmaceutical researchers. The nanoparticles were prepared by solvent evaporation W1/O/W2 emulsion method and in the ratios of 1 to 1, 1 to 2 and 1 to 3 drug to polymer. The production yield, loading efficiency, particle size, poly dispersity index and zeta potential of selected formulation were 84.30%, 80.60%, 192[Formula: see text]nm, 0.18[Formula: see text]mV and [Formula: see text][Formula: see text]mV, respectively. DSC and FTIR studies showed that no chemical interactions between drug and polymer Formulations showed an initial burst release, which is a reason for the good capacity of the polymer to maintain the drug in it and lead to a primary slow release.

DEVELOPMENT AND STATISTICAL OPTIMIZATION OF GASTRORETANTIVE FLOATING MICROSPHERES OF PREGABALIN PREPARED BY W/O/O MULTIPLE EMULSION METHOD

Objective: The aim of this study is to develop a gastroretentive microsphere of pregabalin using design of experiment (DoE) to decrease dosing frequency and increasing bioavailability. Methods: Pregabalin microsphere was prepared by W/O/O multiple emulsion method using a mixture of ethyl cellulose (EC) and polyvinyl pyrrolidone (PVP) as rate-controlling polymer. Mixed solvent system comprising of dichloromethane (DCM) and acetonitrile (ACN) and light liquid paraffin was chosen as primary and secondary oil phase respectively. Taguchi design was employed for factor screening and Box Behnken design was used for the optimisation of critical process parameters. Results: Taguchi design revealed that polymer: drug, DCM: ACN and PVP: EC is the critical factor for the preparation of microspheres. The optimized formulation was prepared using polymer: drug (4.95:1), DCM: ACN (53.76: 46.24) and PVP: EC (2:5) which showed mean particle size of 203.34±4.82 µm, practical yield of 87.52±2.91 %, encapsulation efficiency of 96.43±3.14 %, floating ability up to 90.42±1.64 % and T60% of 332.81±5.84. Drug release from microsphere followed Higuchi Kinetic model. Conclusion: In a nutshell, microspheres with excellent flowability and great encapsulation efficiency were successfully developed. These can be useful in improving patient compliance by reducing frequent dosing.