Programa de intervención farmacéutica periférica para la prevención de anemia ferropénica en niños

Objetivo: El objetivo fue identificar cómo la aplicación de un programa de intervención farmacéutica periférica influye en la prevención de la anemia en niños de 0 a 5 años. Materiales y métodos: El estudio se aplicó bajo un enfoque cuantitativo y fue descriptivo y comparativo. Se realizó un muestreo no probabilístico de tipo intencional. La población fue de 40 niños, con una muestra de 28 niños (de 0 a 5 años) de ambos sexos pertenecientes al asentamiento humano Carlos Manuel Cox, en el distrito de Ancón en la provincia de Lima, Perú. Se aplicaron pruebas hematológicas para medir el nivel de hemoglobina en los niños, así como cuestionarios que resolvieron sus cuidadores o padres. Se sensibilizó sobre la anemia, así como acerca de la parasitosis, alimentos nutritivos, hábitos de higiene control y tratamiento médico y farmacológico. Se aplicó una escala de Likert para la prevención de la anemia ferropénica. Para el análisis de sangre, se procedió con una prueba de microhematocrito para medir la hemoglobina, previa sensibilización sobre la anemia, en la que la toma de muestras estuvo a cargo de un tecnólogo médico junto con las investigadoras. El procesamiento de datos se realizó con los programas SPSS 25.0 y Microsoft Excel. Las correlaciones entre las variables se determinaron mediante el coeficiente de correlación de Pearson. Resultados: Respecto a los resultados de conocimientos sobre anemia, en el pretest se encontró una media de 7,6, con una desviación estándar de 2,5, que después, en el postest, se presentó como 18,0 y 0,0, respectivamente; por lo tanto, no representa un aumento en el conocimiento. Conclusiones: Se determinó que el programa de intervención farmacéutica influye positivamente en el conocimiento de las madres sobre la prevención de la anemia ferropénica en sus hijos.

Objective: To identify how the implementation of a peripheral pharmaceutical intervention program influences the prevention of anemia in children from 0 to 5 years of age. Materials and methods: A quantitative, descriptive and comparative study was conducted with a purposive nonprobability sampling. The study population consisted of 40 children and the sample included 28 children from 0 to 5 years of age, of both sexes, living in the Carlos Manuel Cox shanty town, located in the district of Ancón, province of Lima, Peru. Hematological tests were performed to measure the hemoglobin level in the children, and questionnaires were administered to their caregivers or parents. An awareness program on anemia, parasitosis, nutritious food, good hygiene practices, medical control, and medical and pharmacological treatment was undertaken. A Likert scale was used to determine the prevention of iron deficiency anemia. For blood analysis, a microhematocrit test was performed to measure the hemoglobin levels, prior to the awareness of anemia. The sampling was carried out by a medical technologist together with the researchers. Data processing was conducted using IBM SPSS Statistics V25.0 and Microsoft Excel programs. Correlations between variables were determined using Pearson's correlation coefficient. Results: Concerning the results of knowledge about anemia, a mean of 7.6 and a standard deviation of 2.5 were found in the pretest, and a mean of 18.0 and a standard deviation of 0.0 were found in the posttest, thus there was no increase in knowledge. Conclusions: The pharmaceutical intervention program positively influences the knowledge of mothers about the prevention of iron deficiency anemia in their children.

Comparator product issues for biowaiver implementation: the case of Fluconazole

The aim of this work was to assess if the commercially available Fluconazole drug products (Reference, Generic and Similar) would meet the biowaiver criteria from Food and Drug Administration (FDA) and Brazilian Agency for Health Surveillance (ANVISA) agencies. All formulations were evaluated considering the dissolution profile carried out in Simulated Gastric Fluid (SGF) pH 1.2, Acetate Buffer (AB) pH 4.5 and Simulated Intestinal Fluid (SIF) pH 6.8. The results demonstrated that all formulations fulfilled the 85% of drug dissolved at 30 min criterion in SGF pH 1.2. However, in AB pH 4.5 and SIF pH 6.8, some formulations, including the comparator, did not achieve this dissolution percentage. The discrepant dissolution profiles also failed the ƒ2 similarity factor analysis, since none of the formulations showed values between 50 and 100 in the three dissolution media. Comparative dissolution profiles were not similar, considering that the main issues concerning the dissolution were evidenced for the comparator product. Hence, a revision in the regulatory norms in order to establish criteria to switch the comparator could result in an increased application of drugs based on biowaiver criteria

An update on oral drug delivery

Orally administered drug entities have to survive the harsh gastrointestinal environment, penetrate the enteric epithelia and circumvent hepatic metabolism before reaching the systemic circulation. Whereas the gastrointestinal stability can be well maintained by taking proper measures, hepatic metabolism presents as a formidable barrier to drugs suffering from first-pass metabolism. The pharmaceutical academia and industries are seeking alternative pathways for drug transport to circumvent problems associated with the portal pathway. Intestinal lymphatic transport is emerging as a promising pathway to this end. In this review, we intend to provide an updated overview on the rationale, strategies, factors and applications involved in intestinal lymphatic transport. There are mainly two pathways for peroral lymphatic transport-the chylomicron and the microfold cell pathways. The underlying mechanisms are being unraveled gradually and nowadays witness increasing research input and applications.

Metal-organic frameworks for advanced drug delivery

Metal-organic frameworks (MOFs), comprised of organic ligands and metal ions/metal clusters

Aportes de la biotecnología al diagnóstico y tratamiento de la enfermedad renal crónica y comorbilidades frecuentes / Biotechnology contribution to the diagnosis and treatment of chronic kidney disease and frequent comorbidities

Este trabajo tiene como objetivo revisar las contribuciones de la biotecnología, en relación con el tratamiento, diagnóstico y la monitorización de la enfermedad renal crónica (ERC) y sus comorbilidades más frecuentes, especialmente la anemia. En relación con los tratamientos, enfocamos el desarrollo de productos biofarmacéuticos como los agentes estimulantes de la eritropoyesis (ESA), que fueron los primeros biofármacos utilizados para el tratamiento de la anemia asociada a la ERC; analizamos sus características y utilización actual después de varios años de experiencia clínica, así como también otras alternativas en desarrollo. Revisamos distintos tipos de bioterapias, la utilización de las células estromales mesenquimales de médula ósea (MSC) y tratamientos alternativos con modificaciones dietarias, que se basan en la asociación entre la microbiota intestinal de los pacientes renales crónicos y sus condiciones fisiopatológicas. Finalmente, en relación con el diagnóstico y monitorización, nos referimos al estudio y validación de biomarcadores diagnósticos, predictivos y terapéuticos que han permitido optimizar los resultados clínicos en este tipo de pacientes. (AU)

The aim of this work is to review the contributions of biotechnology, in relation to the treatment, diagnosis and monitoring of chronic kidney disease (CKD) and its most frequent comorbidities, especially anemia. Regarding the treatment, we focus on the development of biopharmaceutical products such as erythropoiesis stimulating agents (ESA), which were the first biopharmaceuticals used to treat anemia associated with chronic kidney disease (CKD). We analyzed their characteristics and their current use after several years of clinical experience, as well as other alternatives in development. We also review different types of biotherapies, the use of bone marrow mesenchymal stromal cells (MSC) and alternative treatments with dietary modifications, which are based on the association between the intestinal microbiota of chronic kidney patients and their pathophysiological conditions. Finally, in relation to diagnosis and monitoring, we refer to the study and validation of diagnostic, predictive and therapeutic biomarkers that have made clinical results possible to be optimized in this type of patient. (AU)

Equilibrium solubility study to determine fexofenadine hydrochloride BCS class and challenges in establishing conditions for dissolution profiles applied to suspension

The aim of this work was to perform solubility studies for fexofenadine hydrochloride and establish dissolution conditions for this drug in oral suspension dosage form. The solubility study was executed through the shake-flask method, below 37 ºC±1 ºC, at 100 rpm stirring for 12 h in three buffer solutions: hydrochloric acid pH 2.0, acetate pH 4.5 and phosphate pH 6.8. The dissolution test was developed in vessels containing 900 mL of the same buffer, employing the paddle apparatus in speed of 25 and 50 rpm, below 37 ºC±0.5 ºC. The drug was classified as low solubility according to the Biopharmaceutics Classification System, since the dose/solubility ratio was higher than 250 mL in all media tested (326.55 mL in buffer pH 2.0; 2,456.33 mL in buffer pH 4.5 and 1,021.16 mL in buffer pH 6.8). The dissolution test showed that a release of 85% in 30 min could be established. The rotation speed of 25 rpm, media volume of 900 mL and insertion of the samples through weighted syringes are adequate. The buffered media pH 2.0 could be chosen as dissolution media.

A systematic evaluation of biopharmaceutics classification system of main efficacy and toxic ingredients in Polygoni Multiflori Radix Praeparata / 中草药

Objective: Biopharmaceutics classification system (BCS) of five main pharmacological/toxic components (gallic acid, emodin, stilbene glycoside, physcion, and emodin-8-O-β-D-glucoside) of Polygoni Multiflori Radix Praeparata (PMRP) were carried out. Methods: The solubility and permeability of each representative component were studied by equilibrium solubility method and everted intestinal sac method, respectively. Using two softwares (Pipeline Pilot 7.5, ChemDraw 7.0) to predict the solubility and permeability parameters of each component. Classical BCS classification of measured and predicted values of representative components was conducted according to Food and Drug Administration (FDA) standards, and their correlation was evaluated. Results: The emodin, emodin-8-O-β-D-glucoside, and physcion in PMRP was preliminary determined as BCS IV drugs. THSG and gallic acid belong to BCS III drugs, and permeability was the main limiting factor in their absorption process. There was software which predicts false positives of anthraquinone in BCS classification studies. Conclusion: In this study, five main pharmacodynamic/toxic components of PMRP were classified by BCS method, which provided data support and technical reference for in vivo absorption prediction and in vitro safety evaluation of traditional Chinese medicine.

Advances in coamorphous drug delivery systems

In recent years, the coamorphous drug delivery system has been established as a promising formulation approach for delivering poorly water-soluble drugs. The coamorphous solid is a single-phase system containing an active pharmaceutical ingredient (API) and other low molecular weight molecules that might be pharmacologically relevant APIs or excipients. These formulations exhibit considerable advantages over neat crystalline or amorphous material, including improved physical stability, dissolution profiles, and potentially enhanced therapeutic efficacy. This review provides a comprehensive overview of coamorphous drug delivery systems from the perspectives of preparation, physicochemical characteristics, physical stability, and performance. Furthermore, the challenges and strategies in developing robust coamorphous drug products of high quality and performance are briefly discussed.

Research and development thought on biopharmaceutics classification system of Chinese materia medica / 中国中药杂志

The biopharmaceutics classification system( BCS) is a scientific framework or method for classifying drugs based on drug solubility and permeability,which can be used to provide drug bioavailability-absorption correlation analysis. Based on the characteristics of multi-component and multi-target of traditional Chinese medicine( TCM) as well as the concept,method and technology of BCS,the research group proposed biopharmaceutics classification system of Chinese materia medica( CMMBCS) and carried out research and data accumulation of classical prescriptions. Based on the previous research results,further development ideas under the CMMBCS concept and framework were further proposed in this study. In the course of research,the influence of the intermediate links of the complex interactions of the multi-component environment was omitted,and the component absorption studies on the main clinical effects of prescription ingredients were directly concerned,or the components and data were reversely extracted from the aspects of metabolism,pharmacodynamic pathways and absorption principles. Studies were conducted from two aspects( single component and compound prescription) to comprehensively evaluate the absorption properties of TCM compound. In the research path,the different ways in which Chinese medicine could exert its efficacy were fully considered,and CMMBCS classification and establishment rules were clarified mainly by focusing on the absorption pathway into the blood. Specifically,the network pharmacology and molecular docking technology were used to screen the compound index components of TCM; the absorption rules were studied by the physiologically based pharmacokinetic models and the absorption parameters of CMMBCS were calculated by reverse reasoning. Then the CMMBCS classification of TCM prescription was corrected by studying the efficacy or absorption pathway. In this paper,the theoretical framework and research methodology of CMMBCS were systematically improved based on the establishment of CMMBCS basic theory,the supplementary of drug-oriented research ideas and the application of modern mature Chinese medicine methodology.

Applicability analysis and evaluation of aglycones in single-pass intestinal perfusion technique based on PBPK model / 中国中药杂志

Single-pass intestinal perfusion( SPIP) is the common carrier of biopharmaceutics classification system( BCS) to study compound permeability. With the application and deepening study of BCS in the field of traditional Chinese medicine( TCM),SPIP model is becoming more and more common to study the intestinal absorption of TCM ingredients. Based on the limitations of the SPIP model in some researches on TCM permeability,it was speculated in this study that aglycone may be more suitable than the glycoside to study the intestinal absorption problem by using SPIP model. Furthermore,applicability of aglycone components was analyzed and evaluated. In this study,with quercetin,daidzein,formononetin,genistein and glycyrrhetinic acid used as research objects,the quantitative study of SPIP was used to evaluate the intestinal permeability of these aglycones and to predict the effective permeability coefficient( Peff) and absorption fraction( Fa) in human body. By combining studies comparison and analysis on multiple permeability research methods and prediction of human body absorption of aglycones in physiological-based pharmacokinetic models,this paper can further illustrate that the SPIP model is a good tool for studying the permeability of aglycones and predicting human absorption,which can provide data foundation and theoretical reference for researches on SPIP technique and BCS in intestinal absorption of TCM ingredients.

Study on biopharmaceutics classification system of Chinese materia medica for Gegen Qinlians Tablets based on anti-inflammatory activity / 中国中药杂志

The research on biopharmaceutics classification system of Chinese materia medica( CMMBCS) should be finally implemented to the holistic research level of traditional Chinese medicine compounds,while the overall biopharmaceutical properties of traditional Chinese medicine compounds are not only the sum of solubility and permeability of each component. In this study,Gegen Qinlian Tablets was used as the research object,and the contents of 12 representative components,i.e. puerarin,daidzin,baicalin,daidzein,wogonoside,baicalein,wogonin,glycyrrhizic acid,coptisine hydrochloride,epiberberine,berberine hydrochloride and palmatine hydrochloride,were simultaneously determined by HPLC to obtain the mass weight of each component. The in vitro lipopolysaccharide( LPS)-induced RAW264. 7 cells inflammation model was established to investigate the anti-inflammatory effects of 12 representative components and obtain the efficacy weight of each component. In order to obtain the number of doses and effective permeability coefficient which can represent the overall biopharmaceutical properties of Gegen Qinlian Tablets,mass weight was combined with efficacy weight to integrate the solubility and permeability data of each component determined by typical shake flask method and in situ single pass intestinal perfusion model respectively. The results indicated that Gegen Qinlian Tablets should be categorized Ⅳ drug of the CMMBCS with low solubility and low permeability.

Research Progress on Biopharmaceutics of Active Ingredients in Chinese Materia Medica Under Multi-component System / 中国实验方剂学杂志

The biopharmaceutical properties (solubility, permeability, etc.) of active pharmaceutical ingredients are playing an important role in understanding of disposition of drugs in the body, screening of drugs and evaluation of drug delivery system. The active ingredients of Chinese materia medica (CMM) are various and complex, the research on biopharmaceutics provides a train of thought and practical method for the prediction and research on the process of active ingredients from CMM in vivo. The multi-components system is one of the main differences between CMM and chemical medicine, and the study on biopharmaceutics of active ingredients in CMM under multi-components system has become a hot topic. The progress on biopharmaceutics of active ingredients in CMM under multi-components system was reviewed in this article, which may provide the reference for data integration, theoretical induction and system construction in this field, and provide new train of thought for the research on CMM theories and the development of CMM in the perspective of biopharmaceutics.

Impacts of multicomponent environment on intrinsic dissolution rate of berberine in biopharmaceutics classification system of Chinese materia medica / 中国中药杂志

To illustrate the intrinsic dissolution rate(IDR) involved in biopharmaceutics classification system of Chinese materia medica(CMMBCS), investigate the effect of artificial multicomponent environment on IDR of berberine, by using a non-disintegrating disk, and summarize related rules by using the obtained data. Progressive levels design was used to investigate the effects of single component environment (puerarin, baicalin, and glycyrrhizic acid); double-component environment(puerarin+baicalin, puerarin+ glycyrrhizic acid, baicalin+glycyrrhizic acid); and triple-component environment(puerarin+baicalin+glycyrrhizic acid) on IDR of berberine, laying a foundation for further researches on the absorption mechanism of multiple components.

Comparison of Two Biopharmaceutics Classification Systems and Discussion of Their Applications / 中国药学杂志

OBJECTIVE: To compare the difference between two kinds of biopharmaceutics classification systems and their applications. METHODS: Literatures and guidelines on biopharmaceutics classification system(BCS) and biopharmaceutics drug disposition classification system(BDDCS) were collected, the differences in conception, classification criteria, and application were compared, and problems which should be paid attention to in application were summarized. RESULTS:A lot of issues such as solubility, permeability, extent of metabolism and so on are involved in the application of BCS and BDDCS. Different classification criteria may have different results. The recognition for the two kinds of pharmaceutics classification systems by different administration organizations is not yet completely consistent. CONCLUSION:BCS and BDDCS play important roles in understanding the properties of drugs, especially in drug development and evaluation of generic drug conformance, however, the source of data should be identified when quoting the data. Possible risks should be considered for rational use of the data.

Dissolution and Permeability Behavior of Diclofenac Sodiumenteric-Coated Tablets In-Vitro / 中国药学杂志

OBJECTIVE: To investigate the permeability of diclofenac sodium(DS)through parallel artificial membrane, and compare the differences in the dissolution rates and fluxes of diclofenac sodium enteric-coated tablets from Novartis in Beijing, Turkey and Germany.METHODS :The permeation of diclofenac sodium in different pH media was studied and determined.The effects of excipients on the permeability of diclofenac sodium were investigated by comparing the differences in the permeability of diclofenac sodium enteric-coated tablets.After being placed in acidic media of pH 6.0 and pH 6.8 for 2 h, the difference in the dissolution profiles and membrane fluxes of three sources diclofenac sodium enteric-coated tablets were determined and compared. RESULTS: The permeability of diclofenac sodium in pH 5.0-6.8 medium increased with the decrease of pH value, which was the smallest in pH 6.8 medium (1.08×10-4 cm•s-1). The excipients did not affect the permeability of the main component. The dissolution rate of the sample from Turkey Novartis was slightly faster than those from Beijing and Germany Novartis. CONCLUSION: The permeability of diclofenac sodium depends on the pH of the medium. The biopharmaceutics classification system(BCS) of diclofenac sodium is classified as class Ⅱ, a drug of low solubility and high permeability. The dissolution of diclofenac sodium enteric-coated tablets depends on the dissolving rate of the enteric-coating and the dissolution rate of the tablet core.The dissolution behaviors of diclofenac sodium enteric-coated tablets from different regions of the same company in pH 6.0 and pH 6.8 media are difference but the membrane fluxes are similar. This study may provide data support for the selection of multi-source reference preparations in the evaluation of generic drug conformance, and plays an important guiding role in prescription screening and bioequivalence risk assessment.

Development, measurement, and application of biopharmaceutics classification system for Chinese materia medica / 中草药

Biopharmaceutics classification system (BCS) is a research method that scientifically classifies drugs based on its solubility and permeability, which is generally applicable to oral chemical products of single-component. Compared with most western medicines, Chinese materia medica (CMM) has a complex system of multiple components, so BCS has certain limitations in the study of CMM. Based on the scientific framework of BCS, domestic scholars have successively proposed some BCS for CMM. This article reviews the development, determination, and application of BCS for CMM by consulting relevant domestic and foreign literatures, in order to lay a reference for the in-depth research of BCS for CMM.

Solubility evaluation of didanosine: a comparison between the equilibrium method and intrinsic dissolution for biopharmaceutics classification purposes

ABSTRACT BCS (Biopharmaceutics Classification System) and BDDCS (Biopharmaceutics Drug Disposition Classification System) were proposed as tools for classifying drugs into four categories. Both systems consider the solubility as an important characteristic for the classification of compounds in drug development and in vivo disposition prediction. Although some results of drug solubility can be found in the literature, the aforementioned characteristic is not entirely clear when considering didanosine (ddI). Based on that, the solubility of ddI was evaluated using equilibrium and intrinsic dissolution methods. For the equilibrium method, excess amount of ddI was added to each media until obtaining a supersaturated solution and the mixture was submitted to agitation at 37 °C. For the intrinsic dissolution method, the drug was compressed into the Wood's apparatus matrix and subjected to dissolution in each media with agitation at 37 °C. The results obtained from the equilibrium method indicated that it was necessary 139.37 mL of pH 1.2 media, 87.72 mL of pH 4.5 media, 12.54 mL of pH 6.8 media, 5.03 mL of pH 7.5 media and 7.65 mL of purified water for drug solubilization. Furthermore, a very fast intrinsic dissolution rate (IDR) was obtained for each media: 0.1 mg/min/cm² (pH 1.2), 0.2 mg/min/cm² (pH 4.5), 0.2 mg/min/cm² (pH 6.8), 0.1 mg/min/cm² (pH 7.5) and 0.1 mg/min/cm² (purified water). Based on these results, ddI can be considered as a highly soluble drug for both equilibrium and intrinsic dissolution methods.

Overall intestinal permeability of multiple components in lotus leaf by in situ single pass intestinal perfusion models / 中国中药杂志

To investigate the overall intestinal permeability of multiple components in lotus leaves and make clear the interaction in composition absorption process. Rat single-pass intestinal perfusion technique was used, and the results showed that the Peff values of nuciferine, demethylanuciferine, rutin, quercetin, kaempferol from lotus leaf were greater than 0.5×10⁻⁴ cm•s⁻¹. In the biopharmaceutics classification system (BCS) intestinal permeability property, these ingredients were high permeable components, while the hyperin was low permeable component. However, in the multi-component environment of the lotus leaf extract, component permeation was changed. Semi quantitative analysis of the unclear components showed that under the multi-component environment, four in seven components with relatively high contents had a Peff value less than 0.5×10⁻⁴ cm•s⁻¹, indicating these 4 components were of low permeability, while other 3 components were of high permeability. The results could be valuable to make clear the overall intestinal permeability of multiple components in lotus leaf, and lay a foundation for studying the mechanism of the lipid-lowering effect of lotus leaf.

In vitro and in vivo intestinal absorption of Huanglian decoction in multi-component environment / 中国中药杂志

The effect of drugs in the body is always inseparable with the dynamic processes of absorption, distribution, metabolism and excretion. For oral drug, absorption, as the first link to enter the body, is particularly valued. Traditional Chinese medicine has multiple components and multiple targets, and the nature of its single composition is different from that in the multicomponent environment. Alkaloids in Huanglian extract was used as the main object in this study to establish an analytical method for determining the content of alkaloids in Huanglian. In addition, the compositions of the Huanglian aqueous extract solution which can be absorbed through intestinal wall into blood, were initially determined by the means of everted gut sac and in intestinal perfusion with venous sampling experiment. This paper can provide data reference and support for the further study on the absorption and metabolism of Huanglian.

The progress of novel drug delivery systems / 药学学报

The development of pharmaceuticals has been providing many kinds of novel drug delivery systems, which are important for improving therapeutic effect and one of the most important fields in pharmaceutics. According to their application, we can generally divide the novel drug delivery systems into three categories:quickly performed drug delivery system, long-term drug delivery system and high effective drug delivery system. Some diseases, such as asthma, angina pectoris and migraine, require therapeutics urgently, and the drugs have to be absorbed in several minutes. Therefore, quickly performed drug delivery systems are developed, such as oral disintegrating tablets and nasal spray. For normal tablets and capsules, especially the drugs with short blood half life, the drug concentration in blood shows obvious peak-valley phenomenon, which reduces the therapeutic effect and requires multiple administration. To solve this problem, sustained drug release system was developed, which could release the drugs slowly and sustainably even in zero-order kinetics. The pulse drug delivery system was developed that can delayed and pulsed release drug for one or several times. This system is especially useful in the management of asthma and heart disease, which are often found in midnight or early morning when patients are in bed. Transdermal drug delivery system could release drugs sustainably and deliver the drugs through skin to blood circulation, providing long term activity. The water-insoluble drugs are difficult for pharmaceutical development, thus many methods were developed to improve the solubility and bioavailability of drugs. Although biopharmaceuticals are important for disease treatment, the application shadows by the poor stability and low bioavailability. Thus the biopharmaceutical delivery system was developed, which mainly focused on structure modification and encapsulation by carriers. Considering therapeutic effect requires interaction between drugs and their targets, it is important to deliver drugs to their targets. Therefore, targeting delivery systems were developed, which mainly based on the nanoparticles. Furthermore, on-demand release drug delivery systems are also developed with the property of environment-triggered drug release. In conclusion, the novel drug delivery systems were reviewed in this study.