A real-time and modular approach for quick detection and mechanism exploration of DPIs with different carrier particle sizes

Dry powder inhalers (DPIs) had been widely used in lung diseases on account of direct pulmonary delivery, good drug stability and satisfactory patient compliance. However, an indistinct understanding of pulmonary delivery processes (PDPs) hindered the development of DPIs. Most current evaluation methods explored the PDPs with over-simplified models, leading to uncompleted investigations of the whole or partial PDPs. In the present research, an innovative modular process analysis platform (MPAP) was applied to investigate the detailed mechanisms of each PDP of DPIs with different carrier particle sizes (CPS). The MPAP was composed of a laser particle size analyzer, an inhaler device, an artificial throat and a pre-separator, to investigate the fluidization and dispersion, transportation, detachment and deposition process of DPIs. The release profiles of drug, drug aggregation and carrier were monitored in real-time. The influence of CPS on PDPs and corresponding mechanisms were explored. The powder properties of the carriers were investigated by the optical profiler and Freeman Technology four powder rheometer. The next generation impactor was employed to explore the aerosolization performance of DPIs. The novel MPAP was successfully applied in exploring the comprehensive mechanism of PDPs, which had enormous potential to be used to investigate and develop DPIs.

Natural ingredients from Chinese materia medica for pulmonary hypertension / 中国天然药物

Pulmonary hypertension (PH) is a severe pathophysiological condition characterized by pulmonary artery remodeling and continuous increases in pulmonary artery pressure, which may eventually develop to right heart failure and death. Although newly discovered and incredible treatment strategies in recent years have improved the prognosis of PH, limited types of effective and economical drugs for PH still makes it as a life-threatening disease. Some drugs from Chinese materia medica (CMM) have been traditionally applied in the treatment of lung diseases. Accumulating evidence suggests active pharmaceutical ingredients (APIs) derived from those medicines brings promising future for the prevention and treatment of PH. In this review, we summarized the pharmacological effects of APIs derived from CMM which are potent in treating PH, so as to provide new thoughts for initial drug discovery and identification of potential therapeutic strategies in alternative medicine for PH.

Novel approach for real-time monitoring of carrier-based DPIs delivery process pulmonary route based on modular modified Sympatec HELOS

An explicit illustration of pulmonary delivery processes (PDPs) was a prerequisite for the formulation design and optimization of carrier-based DPIs. However, the current evaluation approaches for DPIs could not provide precise investigation of each PDP separately, or the approaches merely used a simplified and idealized model. In the present study, a novel modular modified Sympatec HELOS (MMSH) was developed to fully investigate the mechanism of each PDP separately in real-time. An inhaler device, artificial throat and pre-separator were separately integrated with a Sympatec HELOS. The dispersion and fluidization, transportation, detachment and deposition processes of pulmonary delivery for model DPIs were explored under different flow rates. Moreover, time-sliced measurements were used to monitor the PDPs in real-time. The Next Generation Impactor (NGI) was applied to determine the aerosolization performance of the model DPIs. The release profiles of the drug particles, drug aggregations and carriers were obtained by MMSH in real-time. Each PDP of the DPIs was analyzed in detail. Moreover, a positive correlation was established between the total release amount of drug particles and the fine particle fraction (FPF) values ( = 0.9898). The innovative MMSH was successfully developed and was capable of illustrating the PDPs and the mechanism of carrier-based DPIs, providing a theoretical basis for the design and optimization of carrier-based DPIs.

Functional prediction of Tanreqing Injection in brain diseases / 中国中药杂志

The study explores the application of Tanreqing Injection into brain components in brain diseases. The components of Tanreqing Injection and its existing components in rat cerebrospinal fluid were qualitatively analyzed by liquid chromatography-mass spectrometry(LC-MS). The possible mechanism of action of Tanreqing Injection into brain on brain diseases was predicted by network pharmacological theory. In this study, 17 brain-entry components of Tanreqing Injection were founded, and 222 core targets were obtained from network pharmacological results. The biological processes include 31 items such as negative regulation of apoptotic process, MAPK cascade, Ras protein signal transduction, and 22 items such as PI3 K-Akt signal transduction, MAPK signal transduction and neurotrophic factor signal transduction. Nine brain diseases including stroke, migraine and meningioma were screened out by predicting the effect of Tanreqing Injection on brain components, which provide ideas and directions for further study of a certain encephalopathy and lay a theoretical foundation for further revealing its molecular mechanism.

Deep learning for prediction of pharmaceutical formulations

Current pharmaceutical formulation development still strongly relies on the traditional trial-and-error methods of pharmaceutical scientists. This approach is laborious, time-consuming and costly. Recently, deep learning has been widely applied in many challenging domains because of its important capability of automatic feature extraction. The aim of the present research is to apply deep learning methods to predict pharmaceutical formulations. In this paper, two types of dosage forms were chosen as model systems. Evaluation criteria suitable for pharmaceutics were applied to assess the performance of the models. Moreover, an automatic dataset selection algorithm was developed for selecting the representative data as validation and test datasets. Six machine learning methods were compared with deep learning. Results showed that the accuracies of both two deep neural networks were above 80% and higher than other machine learning models; the latter showed good prediction of pharmaceutical formulations. In summary, deep learning employing an automatic data splitting algorithm and the evaluation criteria suitable for pharmaceutical formulation data was developed for the prediction of pharmaceutical formulations for the first time. The cross-disciplinary integration of pharmaceutics and artificial intelligence may shift the paradigm of pharmaceutical research from experience-dependent studies to data-driven methodologies.

The use of the software JST-XRD for identification of crystalline phases in pharmaceutical raw materials and tablets / Uso do software JST-XRD para identifcação de fases cristalinas em insumos farmacêuticos e medicamentos

Study of polymorphism is of great importance for the pharmaceutical industry once polymorphs may display different physicochemical properties, which, in turn, may result in stability differences that can bring problems for the manufacturing stages and the quality of fnal products. Although research on organic polymorphs has greatly increased in the last decades, it still does not cover all needs for the pharmaceutical market. Techniques such as spectroscopy in the infrared region, nuclear magnetic resonance, thermal analysis, X-ray diffraction, etc., can be used to identify polymorphism. The polymorphism is a property of the crystalline solid state, and can be evaluated by X-ray diffraction once each polymorph exhibits one specifc X-ray diffraction pattern. The JST-XRD program is a tool designed to help the identifcation of crystalline phases (including polymorphs) present in pharmaceutical ingredients and tablets by using X-ray diffraction data obtained from scientifc articles and patents. This paper presents new implementations for the JST-XRD and describes its use in the analysis of active pharmaceutical ingredient and marketed tablets of norfloxacin, mebendazole and atorvastatin calcium. By the means of comparison, JSTXRD allowed identifying the crystalline phases in the diffraction patterns of the analyzed drugs, showing the program suitability for polymorphism research, pre-formulation and quality control in pharmaceutical industries. JST-XRD can also be used for educational purposes in undergraduate and graduate programs in order to show the potentiality of X-ray powder diffraction in polymorphism analysis.(AU)

O estudo do polimorfsmo é de grande importância na indústria farmacêutica porque os polimorfos podem apresentar diferentes propriedades físico-químicas, podendo resultar em diferenças na estabilidade e desse modo causar problemas nas etapas de manufatura e no produto fnal. Embora a pesquisa de moléculas orgânicas que apresentam polimorfsmo tenha aumentado bastante nas últimas décadas, ainda não contempla todas as necessidades do mercado farmacêutico. Para a identifcação de polimorfsmo podem ser utilizadas técnicas como espectroscopia na região do infravermelho, ressonância nuclear magnética, análise térmica (DSC), difração de raios X, etc. O polimorfsmo, por ser uma propriedade do estado sólido e cristalino, pode ser avaliado através da difração de raios X, já que cada polimorfo apresenta um padrão de difração de raios X único. O programa JST-XRD é uma ferramenta projetada para auxiliar a identifcação de fases cristalinas, incluindo polimorfos, presentes em insumos farmacêuticos e comprimidos, usando dados de difração de raios X obtidos em artigos científcos e patentes. Esse trabalho apresenta novas implementações no JST-XRD e descreve seu uso na análise de amostras de princípio ativo e comprimidos comerciais de norfloxacino, mebendazol e atorvastatina cálcica. Através das comparações realizadas, JSTXRD permitiu identifcar todas as fases cristalinas dos difratogramas dos fármacos analisados, mostrando que o programa é adequado para pesquisa em polimorfsmo; na pré-formulação e controle de qualidade em indústrias farmacêuticas, assim como para uso didático em cursos de graduação e pós-graduação a fm de mostrar as potencialidades da difração de raios X na análise de polimorfsmo.(AU)

Qualitative Detection for Polymorphs in Solid Pharmaceutical Preparations by PXRD / 医药导报

Objective To establish a method for qualitative identification of polymorphs in pharmaceutical solid preparations of active pharmaceutical ingredients ( API ) . Methods We obtained the powder diffraction patterns of the polymorphic drug substance like nimodipine and roxithromycin in solid preparation material and completed quantitative identification for polymorphs by the quantitative detection and using PXRD technology, deduction calculation through the powder X-ray diffraction and comparing with standard diagram. Results Through the analysis of nimodipine and roxithromycin which came from 27 batches of solid preparations from 11 different manufacturers, and comparing to the standard patterns of pure polymorphs, the quantitative identification of different crystalline states of API in pharmaceutical preparations had been established. Conclusion The qualitative detection method for polymorphs of API in pharmaceutical preparations by powder X-ray diffraction has wide applicability and high accuracy, which can be used to identify the polymorphism of API in solid preparation,and also used to control the quality of solid preparations commonly as a qualitative analysis method.