Preformulation studies for the development of a microemulsion formulation from Ambrosia peruviana All, with anti-inflammatory effect

Abstract Natural products are considered an important source of the therapeutic arsenal currently available. Among these alternatives are the seeds of Ambrosia peruviana (altamisa), whose extract has shown an anti-inflammatory effect. The main objective of this work was to perform a preformulation study of Ambrosia peruviana seeds ethanolic extract, where the main factors that affect the physical, chemical, and pharmacological stability of the extract were evaluated, as well as a compatibility study by differential scanning calorimetry (DSC) analysis against different excipients. A dry extract was obtained by rotary evaporation of the seeds macerated with 96% ethanol. The anti-inflammatory activity was determined by measuring its effect on NO production in RAW 264.7 macrophages, stimulated with LPS. The results showed that the dry extract maintained its stability over time when stored at a temperature of 4 and 25ºC, demonstrating its biological activity, the content of phenolic compounds, and its physicochemical parameters remain practically invariable. However, when exposed to high temperatures (60 ºC) it was affected. The thermal analysis revelated that the behavior of most of the selected excipients and the dry extract was maintained, which indicates that it did not present incompatibilities, therefore they can be candidates for formulating a microemulsion.

Compatibility and stability studies involving polymers used in fused deposition modeling 3D printing of medicines / 药物分析学报

One of the challenges in developing three-dimensional printed medicines is related to their stability due to the manufacturing conditions involving high temperatures.This work proposed a new pro-tocol for preformulation studies simulating thermal processing and aging of the printed medicines,tested regarding their morphology and thermal,crystallographic,and spectroscopic profiles.Gener-ally,despite the strong drug-polymer interactions observed,the chemical stability of the model drugs was preserved under such conditions.In fact,in the metoprolol and Soluplus? composition,the drug's solubilization in the polymer produced a delay in the drug decomposition,suggesting a pro-tective effect of the matrix.Paracetamol and polyvinyl alcohol mixture,in turn,showed unmistakable signs of thermal instability and chemical decomposition,in addition to physical changes.In the presented context,establishing protocols that simulate processing and storage conditions may be decisive for obtaining stable pharmaceutical dosage forms using three-dimensional printing technology.

Antimicrobial Effect of Essential Oil of Thymus capitatus from Northern Cyprus and Its Gargle Preformulation

Aims:Theaim of this study is to prepare herbal gargle preformulations making use of essential oil of aerial parts of Thymus capitatusgrowing wild in Northern Cyprus and comparing antimicrobial efficacy between these formulationswith pure essential oil.Place and Duration of Study: Department of Pharmaceutical Technology, Faculty of Pharmacy, Near East University, Nicosia, TRNC and Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Ankara University, Ankara, Turkey, between January 2017 and June 2017.Methodology: Preformulations with three different concentrations of Thymus capitatusessential oil were prepared by using simple preparation method.Preformulation studies were done in lab with less than 500ml. There is not specific process parameters. Manufacturing process and process parameters will be clarified with further studies.These compositions and the essential oil were tested in-vitrofor antimicrobial activity studies by using broth microdilution method. Staphylococcus aureusATCC 43300, Staphylococcus aureusATCC 25923, Staphylococcus epidermidisATCC 12228, Bacillus subtilisATCC 6633, Escherichia coliATCC 25922, Enterococcus faecalisATCC 29212, KlebsiellapneumoniaeRSKK 574, Salmonella paratyphiC, Pseudomonas aeruginosaATCC 9027, Pseudomonas aeruginosaATCC 27853 as bacteria and Candida albicansATCC 10231, Candida parapsilosisATCC 22019 as yeasts were used for antimicrobial activity tests. Results: All trialswere found to be more effective than EO, and a significant effect was observed when compared to the values of standard antimicrobial agents.Conclusion:TheThymus capitatusgrowing in Northern Cyprus could be used as a herbal raw material, essential oil source in developing herbal gargle preformulationsto reduce fungal and bacterialinfections in mouth

A preformulation strategy for the selection of controlled-release components to simulate a subcutaneous implant / Una estrategia de preformulación para la selección de componentes de liberación controlada para simular un implante subcutáneo

Many chronic diseases require repetitive injections as maintenance treatment. It is therefore important to investigate a possible alternative. A simulated subcutaneous implant prototype was fabricated as a polymer matrix covered by cylinder-shape tubing having a porous membrane. Sucrose, bovine serum albumin, and gelatin were selected as matrix excipients. Eight APIs with different physiochemical properties were used to investigate the releasing mechanism. Drug release was tested through an in vitrodissolution apparatus. Drug release of eight APIs followed zero-order kinetics with a minimum 12-hour duration. Release rates also showed linear correlations with the APIs' solubilities under physiological pH. For releasing mechanism studies, different combinations of matrix and membrane were investigated in detail. A 144-hour continuous zero-order release of caffeine was achieved as the best controlled simulated prototype. The results showed that drug release of our simulated prototype was primarily achieved by drug diffusion rather than dissolution.

Muchas enfermedades crónicas requieren inyecciones repetitivas como tratamiento de mantenimiento. Por lo tanto, es importante investigar una posible alternativa. Se fabricó un prototipo de implante subcutáneo simulado a partir de una matriz de polímero cubierta por un tubo en forma de cilindro que tiene una membrana porosa. La sacarosa, la albúmina de suero bovino y la gelatina se seleccionaron como excipientes matriciales. Se utilizaron ocho APIs con diferentes propiedades fisicoquímicas para investigar el mecanismo de liberación. La liberación del fármaco se probó a través de un aparato de disolución in vitro. La liberación del fármaco de las ocho APIs siguió una cinética de orden cero con una duración mínima de 12 horas. Las tasas de liberación también mostraron correlaciones lineales con las solubilidades de las APIs a pH fisiológico. Para los estudios de mecanismos de liberación, se investigaron en detalle diferentes combinaciones de matriz y membrana. El prototipo simulado con mejor control logró una liberación continua de cafeína de orden cero durante 144 horas. Los resultados mostraron que la liberación del fármaco del prototipo simulado ocurrió principalmente mediante la difusión del fármaco en lugar de la disolución.

Pre-formulation physicochemical properties of component-based Chinese medicine of Qinqi Fengshi Fang / 中国中药杂志

Pre-formulation physicochemical properties of the component-based Chinese medicine of Qinqi Fengshi Fang were investigated to provide a research basis for the design of the dosage form for component-based Chinese medicine of Qinqi Fengshi Fang. The macroporous resin adsorption and refining technology was used to prepare the total glycosides extract of Gentianae Macrophyllae Radix, Panacis Majoris Rhizome and Corni Fructus respectively in the prescription of Qinqi Fengshi Fang. Their physicochemical properties were investigated, including solubility, wettability, hygroscopicity, equilibrium solubility, oil-water partition coefficient, and stability. The results showed that the total glycosides of Gentianae Macrophyllae Radix, Panacis Majoris Rhizome and Corni Fructus all had good solubility and wettability. The solubility index of each total glycoside component was greater than 85%, and the water absorption index was greater than 50%. In the range of pH 2.0-7.4, the equilibrium solubility of three kinds of total glycosides all increased with the increase of pH, showing a consistent change trend of solubility. The hydrophilicity was also suitable and similar. Overall, three kinds of total glycosides showed good stability, but strong hygroscopicity. The degree of hygroscopicity was as follows: total glycosides of Gen-tianae Macrophyllae Radix > total glycosides of Corni Fructus > total glycosides of Panacis Majoris Rhizome. Therefore, the hygroscopi-city needed to be considered in the preparation of the component-based Chinese medicine of Qinqi Fengshi Fang. The excipients and packaging materials can be properly selected to reduce the hygroscopicity of the preparation. This study provides a reference for the dosage form design of the component-based Chinese medicine of Qinqi Fengshi Fang.

Preformulation study of hydroxytyrosol butyrate / 国际药学研究杂志

Objective: To determine the apparent oil/water(O/W)partition coefficient of hydroxytyrosol butyrate(HT-Bu), and investigate the solubility, dissolution tendency and stability of HT-Bu in different buffers, so as to provide theoretical basis for the preparation research of HT-Bu. Methods: The appearance and solubility of HT-Bu were investigated, and a high performance liquid chromatography(HPLC)method was established for the quantitative determination of HT-Bu. The solubility and O/W partition coefficient of HT-Bu in different pH buffer solutions were determined by the shakeing flask method. Results: HT-Bu was slightly yellow-colored, viscous, odorless and tasteless oily liquid. The quantitative HPLC method for the HT-Bu determination showed a good linearity within the concentration range of 5-50 μg/ml(r=0.9998). The apparent O/W partition coefficient of HT-Bu was 1.0. In the acetonitrilewater(60:40, V/V) solution, HT-Bu was stable within 12 hours at room temperature. In the different pH buffer solutions(pH 2.0-9.0), the solubility of HT-Bu increased at first and then decreased with the increase of the solution pH. HT-Bu was unstable at pH 5.5, with a large amount decomposed after kept in the solution for 6 h. HT-Bu was stable at pH 8, 0 giving a little amount decomposed after 12 h in the solution, and stable at pH 7.4 showing no significant decomposition after 12 h keeping in the solution. Conclusion: HT-Bu showed a good water solubility, which is unstable in acidic and alkaline solutions.

Preformulation study on novel antischizophrenic drug DT-195 / 国际药学研究杂志

Objective: To perform a preformulation study for the novel antischizophrenic drug DT-195, so as to provide information for its formulation development. Methods: The scanning electron microscopy, X-ray powder diffraction, and the differential scanning calorimetry were used to characterize the appearance and crystalline form of DT-195, and the solubility was tested for DT-195 in different solutions. An HPLC method was established for the preformulation determination of DT-195. The apparent oil/water(O/W) partition coefficient of DT-195 and the equilibrium solubility of the drug under different pH conditions with high and low ion concentrations were determined using the established HPLC method. Results: DT-195 was an off-white crystalline powder, slightly soluble in water, with a good linearity with the peak area within the concentration range of 10-280 μg/ml(r=0.9997)in the HPLC analysis. DT- 195 was stable under acidic conditions and easily degradable under alkaline conditions. The apparent O/W partition coefficient of DT- 195 was 0.23. The solubility of DT-195 in solution decreased with the increase in the solution pH value or ion concentration. Conclusion: The established HPLC method is reliable for the determination of DT-195 and related substances with the high sensitivity, good specificity and the good separation of DT-195 and related substances. The present results have shown that DT-195 is a poorly soluble drug, and thus the improvement of DT-195 solubility in oral preparations will enhance the bioavailability in vivo.

Preformulation study on antirheumatic drug DK-507 / 国际药学研究杂志

Objective To perform a preformulation study for a new antirheumatic drug DK-507 so as to provide theoretical basis for its preparation research.Methods The appearance,crystal form and solubility of DK-507 were investigated.A high perfor-mance liquid chromatography(HPLC)method for the quantitative determination of DK-507 was established.The apparent oil/water (O/W)partition coefficient of DK-507 and the equilibrium solubility of the drug under different pH conditions were determined. Re-sults DK-507 is a white crystalline powder,which is odorless,tasteless and insoluble in water.The quantitative HPLC method for the DK-507 determination showed a good linearity in the range of 10-80 μg/ml(R=0.9998).The apparent O/W partition coefficient of DK-507 was determined to be 1.80.In the different pH solutions,the solubility of DK-507 showed a W-form change,with poor solubili-ties in lower pH solutions,which showed a gradient improvement with the increase of the solution pH values.Conclusion The quanti-tative HPLC method for the DK-507 determination,established in this study,is accurate and reliable.The present results indicate that DK-507 is a water-insoluble drug,and according to the O/W partition coefficient,DK-507 seems likely to be prepared into oral solid preparations.

Preformulation study on novel antiviral drug GZ914 / 军事医学

Objective To study the physical-chemical parameters of antiviral drug GZ 914 and provide data for the preparation design .Methods The appearance , crystal structure and solubility of GZ 914 were investigated .An HPLC method was established to determine the content of GZ 914 in vitro before oil/water partition coefficient and solubility in different pH experiments were calculated .Results GZ914 was a straw yellow powder with a crystalline structure , low water-solubility and good lipotropy .The HPLC method had a good linear relationship within the range of 12-60 μg/ml (r=0.9998).The oil/water partition coefficient of GZ914 was 1.9.Conclusion This analytical method is accurate and reliable.The oil/water partition coefficient indicates that the drug could be formulated as an oral solid preparation.

Determination of Equilibrium Solubility and Apparent Oil/Water Partition Coefficient of Nebivolol Hydrochloride / 中国药师

Objective:To determine the equilibrium solubility and the apparent oil/water partition coefficient of nebivolol hydrochloride to provide experimental basis for the development of new preparations.Methods:The concentration of nebivolol hydrochloride was determined by an HPLC method,and a saturated solution method and a shake-flask method were respectively applied to determine the equilibrium solubility and the apparent oil/water partition coefficient of nebivolol hydrochloride in water,0.1 mol·L-1 HCl solution and phosphate buffer solution with different pH values(pH2.0,pH6.8,pH7.4 and pH8.0).Results:At (37±0.5)℃,the equilibrium solubility of nebivolol hydrochloride in water and in 0.1 mol·L-1 HCl solution was 722.53 μg·ml-1and 56.07μg·ml-1,respectively.The apparent oil/water partition coefficient (Log P) of nebivolol hydrochloride was 1.17 and 1.32,respectively.Within the pH range of 2.0-7.4,with the increase of pH value, the equilibrium solubility and the Log P decreased and increased,respectively,while pH value increased from 7.4 to 8.0,the equilibrium solubility of nebivolol hydrochloride increased and Log P decreased.Conclusion:The method is accurate and reliable.Nebivolol hydrochloride has poor water solubility,and the equilibrium solubility and the Log P are both influenced by pH values.

Preformulation study on anti-smallpox drug tecovirimat / 国际药学研究杂志

[Abstact] Objective To study the preformulation properties of tecovirimat for formulation design. Methods The appear?ance,crystal structure,solubility and permeability of the drug were investigated. The UV method was established to determine the con?tent of tecovirimat in vitro. The solubilization experiment was also conducted. Results Tecovirimat is white and odorless powder with crystalline hydrate structure and low water-solubility with high permeability. The morphology of tecovirimat is six-prismatic-shape. The linearity range of established UV method was 4.14-24.83μg/ml(r=0.9996). The 1∶1 soluble complex was formed with tecovirimat and hydroxypropyl-β-cyclodextrin. Conclusion Tecovirimat is poorly water-soluble drug with high permeability and the established meth?od could be used to determine the content of the drug. Hydroxypropyl-β-cyclodextrin could be used for the solubilization of tecovirimat.

Preformulation study on anti-smallpox drug tecovirimat / 国际药学研究杂志

Objective To study the preformulation properties of tecovirimat for formulation design. Methods The appearance, crystal structure, solubility and permeability of the drug were investigated. The UV method was established to determine the content of tecovirimat in vitro. The solubilization experiment was also conducted. Results Tecovirimat is white and odorless powder with crystalline hydrate structure and low water-solubility with high permeability. The morphology of tecovirimat is six-prismatic-shape. The linearity range of established UV method was 4.14-24.83 µg/ml(r=0.9996). The 1:1 soluble complex was formed with tecovirimat and hydroxypropyl-β-cyclodextrin. Conclusion Tecovirimat is poorly water-soluble drug with high permeability and the established method could be used to determine the content of the drug. Hydroxypropyl-β-cyclodextrin could be used for the solubilization of tecovirimat.

Preformulation study and influence of DMSO and propylene glycol on the antioxidant action of isocoumarin paepalantine isolated from Paepalanthus bromelioides

AbstractCoumarins are phenolic compounds and have various biological properties, including antioxidant activity. The isocoumarin paepalantine, isolated from of Paepalanthus bromelioides Silveira, Eriocaulaceae, exhibits a wide range of biological activities, including antimicrobial, anti-inflammatory, antioxidant and cytotoxic properties. Studies on paepalantine often use dimethylsulfoxide as a solvent. However the dimethylsulfoxide interferes with antimicrobial, cytotoxic and antioxidant assays. Thus, this study aims to evaluate alternative solvents for paepalantine and evaluate their potential to interfere with antioxidant assays (ABTS•+, O2•-, HOCl). Of the selected solvents, propylene glycol had good solubility and remained stable throughout the study period. The results suggested that there is no interference from propylene glycol in antioxidant assays, while dimethylsulfoxide significantly interfered with the HOCl assay. The antioxidant assays showed that paepalantine demonstrated similar or even better antioxidant activity than Trolox. Thus, propylene glycol may be the solvent of choice for paepalantine, a compound that has significant biological potential.

Approaches to pre-formulation R and D for phytopharmaceuticals emanating from herb based traditional Ayurvedic processes.

Botanicals constitute a large part of the drugs from the traditional medicine (TM) and ethno medicine (EM) known for their history of safe use (HOSU). Phytopharmaceuticals having a base of such origin offer high advantages as they come with safety profi les, and often allow extrapolation of the HOSU data, under certain circumstances. However, while current pharmaceutical technologies are being adopted by the industry to make phytopharmaceuticals with such origin, there is a need for preformulation research and development (R and D) during formulation. Some suggestions for R and D studies in case of aqueous extracts known in Ayurveda, converted on an industrial scale to obtain a phytopharmaceutical, and formulated as a solid dosage form (granules, tablets, or capsules) are discussed.

Preformulations studies and preperation of dithranol loaded solid lipid nanoparticles.

Dithranol belongs to the keratolytic category, which is widely used drug in the treatment of psoriasis. The drug is practically insoluble in water. Many conventional dosage forms for psoriasis treatment have been have been formulated earlier, but they did not show good results. Hence in the present study, it was attempted to formulate dithranol in the form of solid lipid nanoparticle. Solid lipid nanoparticles of dithranol were obtained by adaption of lipid dispersion method. Preformulation studies were performed to check the compatibility of drug and excepient for the preparation of formulation by DSC and no interaction was found. Solubility study, partition coefficient determination, UV analysis, HPLC study, FTIR study were also performed. After the preformulation studies Dithranol loaded solid lipid nanoparticles was also prepared. Hence it was concluded that solid lipid nanoparticle of dithranol could be formulated.

Preformulación de tabletas de Tamarindus indica L. / Preformulation of tablets from Tamarindus indica L.

Se realizó un estudio de preformulación de tabletas partiendo del extracto blando de las hojas de la especie Tamarindus indica L. Se estudiaron posibles interacciones en mezclas binarias del extracto blando con los excipientes en relación 1:3 que puedan afectar la cantidad de polifenoles en la mezcla a temperaturas 30, 45 y 60 ºC. Se diseñaron 3 formulaciones preliminares de tabletas y se estudió en todos los casos la calidad de los granulados y de las tabletas. En conclusión, no se producen interacciones que afecten el color, el olor ni la concentración de polifenoles en las mezclas binarias extracto blando de tamarindo-excipientes a 30 ºC, y a temperaturas mayores se reduce la cantidad de polifenoles en las mezclas. La formulación preliminar número tres produce tabletas de calidad tecnológica y resulta adecuada para los subsecuentes estudios de formulación y optimización de tabletas de tamarindo.

A pre-formulation study for tablet preparation using soft extract from Tamarindus indica L. leaves was conducted. Possible interactions in binary mixtures of Tamarindus indica L. soft extract and selected excipients in a 1:3 ratio, which may affect the amount of polyphenols in the mixture at 30°, 45° and 60 °C temperatures, were analyzed. Three preliminary tablet formulations were designed and then the quality of granules and tables were researched in all the cases. It was concluded that there were no interactions affecting the color, the smell and the polyphenol concentration in the evaluated binary mixtures at 30°. At higher temperatures, the amount of polyphenols decreased. Pre-formulation number 3 yielded the best technological quality in tablet production and thus can be used for future formulation and optimization studies of Tamarind tables.

Estudos de pré-formulação de cápsulas gelatinosas duras contendo formulação de extrato de Gymnema sylvestre em pó / Preformulation studies of Gymnema sylvestre extract powder formulation for hard gelatin capsules

Gymnema sylvestre extract (GSE) is a plant product widely used as an adjuvant in the treatment of diabetes mellitus and commercially available as a powder. Owing to its low flowability, the manufacturing of hard gelatin capsules containing GSE faces specific problems. The purpose of this study was to investigate the best excipient (starch, lactose or microcrystalline cellulose) for hard gelatin capsules containing GSE. The technological properties such us bulk density (ñâ); tapped density (ñt); inter-particle porosity (Ie); Carr index (CI); Hausner ratio (HR); loss on drying (%LOD) and particle size distribution (%Pf) of the various GSE mixtures were investigated with the aim of identifying the best excipient. The need for lubricants (talc/magnesium stearate) was also assessed. GSE was characterized as a fine powder with more than 50% of its particles between 0.149mm to 0.250mm; furthermore, CI=25.6%; RH=1.3 and Ie = 25.6% and, as expected with such properties, it showed poor flowability. All the excipients investigated were able to change the technological properties of GSE and the powder mixture containing microcrystalline cellulose gave the best results.

O extrato seco de Gymnema sylvestre (EGS) é um produto fitoterápico amplamente utilizado como adjuvante no tratamento da diabetes, sendo comercializado na forma de pó. O objetivo do presente estudo foi investigar a influência da adição de adjuvantes (amido, lactose ou celulose microcristalina) à formulação para a preparação de cápsulas gelatinosas duras contendo o EGS. As propriedades tecnológicas como densidade aparente (Da), densidade aparente de compactação (Dc), porosidade interparticulas (Ie), Índice de Carr (IC), Fator de Hausner (FH), perda por dessecação (PD%) e análise do tamanho de partículas (%Pf) das diferentes misturas preparadas foram investigadas com o objetivo de escolher o melhor excipiente. A necessidade de agentes lubrificantes (talco/estearato de magnésio) também foi avaliada. O EGS foi caracterizado como um pó fino, com mais de 50% do material particulado compreendido entre 0,149-0,250mm; IC=25,6%; FH=1,3 and Ie = 25,6%, o que justifica seu fluxo pobre. Todos os excipientes testados foram capazes de modificar as propriedades tecnológicas do EGS, sendo a mistura de pós que apresentou melhores resultados aquela obtida com a adição de celulose microcristalina.

Estudio de prefrrmulación para el desarrollo deun gel a base de polímeros con capacidad mucoadhesiva para ensayos de alelopatía en invertebrados mriinos. / Preformulation study for the development of a polymer-based gel with mucoadhesive propierties for its use in allelopathy assays in marine invertebrates

La investigación se desarrolló con el fin de implementar una metodología que permitiera la realización de ensayos de interacciones alelopáticas entre corales y esponjas, minimizando la interacción física provocada por el uso de dispositivos que producen roce y efecto abrasivo sobre los pólipos del coral. Se llevó a cabo un estudio de preformulación utilizando polímeros con características mucoadhesivas sobre mucus que recubre los pólipos de coral, con el fin de obtener un gel, incorporando en las formulaciones un extracto de la esponja Cliona delitrix. Se caracterizaron propiedades como extensibilidad y adherencia, así como la capacidad bioadhesiva de las formulaciones propuestas, considerando su comportamiento reológico. Estas mostraron una buena estabilidad física frente a las condiciones del medio marino tanto in vitro como in situ. De igual manera, se diseñó un dispositivo que facilitó la aplicación del gel sobre la superficie de los corales por parte de los buzos en el arrecife coralino. Finalmente se estudió el comportamiento de liberación al medio acuoso simulado del gel con el extracto de la esponja objeto de estudio.

This study was carried out with the purpose of implementing a methodology to assess allelopathic interactions assays between corals and reef sponges reducing the physical interaction caused by the use of devices that involve abrasion and harm over the coral polyps. Was carried out a preformulation study using polymers with mucoadhesive on the mucus that cover the coral polyps, with the purpose of develop a gel, incorporating an extract from Cliona Delitrix into the formulations. Obtained formulations were characterized by properties such as extensibility, adherence and mucoadhesive capacity. These formulations showed great physical stability under prevalent marine conditions both in vitro and in situ. In the same way was designed a device that let the smearing of the gel over the coral surfaces carried out for the divers in the coral reefs. Finally, was studied the releasing behavior of the gel with the sponge´s extract into the sea water conditions.