Excipients Research Articles

Nifuroxazide Pharmaceutical Preparations in the Russian Federation. Publication One: Nomenclature, Chemical and Pharmaceutical Characteristics of the Preparations’ Composition

One of the most used antimicrobial nitrofurans in Russian medical practice is nifuroxazide, which is distinguished by high therapeutic efficacy, drug safety, as well as economic availability in the treatment of acute bacterial diarrhea without deterioration of the general condition, fever, and intoxication. In the Russian Federation (RF), nifuroxazide preparations in general circulation are supplied by 19 domestic and foreign pharmaceutical organizations. The aim of this study was to analyze the nomenclature, as well as chemical and pharmaceutical characteristics of excipients (EXs) in the composition of nifuroxazide preparations, which received state registration in the RF. A comparative study of the chemical and pharmaceutical characteristics of EXs of 42 nifuroxazide preparations in the form of capsules, tablets, and suspension for oral administration was carried out. The pharmaco-economic status is noted and the demand prospects for all forms of nifuroxazide preparations in the RF are outlined. Quantitative and qualitative differences in the composition of the EXs of a number of nifuroxazide preparations in the form of capsules and suspensions has been shown.

Near Infrared Spectroscopy: Applications In Pharmaceutical Industry

This work explores the comprehensive development of a near infrared (NIR) spectroscopic analytical technique for high-throughput applications for the determination of pharmaceutical raw materials and excipients in a pharmaceutical formulation. Advancements in the NIR spectrometry as quality and process control tool have been discussed. The applications include analyses of different types of samples, manufacturing and identification of active pharmaceutical ingredients based on specified experimental design. The samples were measured in diffusion or reflectance mode in a fourier-transform NIR spectrometer. Additionally, chemometric software was employed for quantitative interpretation of bands. The spectrometry can be utilized for identification of raw materials, their size, polymorphism and blend homogeneity.

The embodiment of the strategy of “using active chemicals as excipients” in compound preparation

The embodiment of the strategy of “using active chemicals as excipients” in compound preparation

Excipient profile and future possibilities of fucoidan: a review

Excipient profile and future possibilities of fucoidan: a review

Pfizer signs with Croda for vaccine excipients

Pfizer signs with Croda for vaccine excipients

Assessment of the applicability of HLB values for natural phospholipid emulsifiers for preparation of stable emulsions.

Natural phospholipid (PL) excipients are native, biocompatible and relatively inexpensive alternatives to synthetic emulsifiers. A well-known PL excipient is lecithin, which primarily contains phosphatidylcholine (PC) and (depending on the purity grade) also contains a well-defined mixture of other PLs with a fatty acid composition, which reflects their natural source. Since all of these lipid species are emulsifiers, natural PLs can be considered as a mixture of (co-) emulsifiers. Many different HLB values for lecithins are given in the literature, which is why this needs to be clarified. To assess this, HLB values of thirteen different plant derived PLs differing in PC content were determined using a centrifugation stress method to determine the relative stability of an emulsion with the respective emulsifier and different oil phases. It could be shown that the studied PLs can be characterized by a broad HLB range, which may be linked to the composition of the PLs and the oil used. In order to emphasize the results of the HLB determination, it could be demonstrated that stable emulsions could be prepared with a wide range of oils using the plant-based PLs and that the preparation method of the emulsions is important in order to obtain stable emulsions. Therefore, assigning a specific exact HLB value to natural PLs instead of a wider range is inappropriate. The broad HLB ranges indicate the suitability of the studied PL emulsifiers for the preparation of oil-in-water emulsions for a wide range of oils: It is recommended to experimentally evaluate the suitability of these natural emulsifiers for the preparation of stable emulsions and to benefit from the wide range of HLB values of these emulsifiers instead of relying on inaccurate and confusing HLB values in the literature.

Development and Validation of a Liquid Chromatographic Method for Concurrent Assay of Weakly Basic Drug Verapamil and Amphoteric Drug Trandolapril inPharmaceutical Formulations

The analysis of weakly basic drugs such as verapamil by reverse-phase liquid chromatography remains a problem, particularly when present in combination with other drugs such as amphoteric compounds like trandolapril. In this study, the simple, accurate, precise and fully validated RP-LC method for the simultaneous determination of verapamil and trandolapril in combined dosage forms has been developed. The LC method allowed quantitation over the ranges of 0.50-18.00 μg/mL and 0.05-1.00μg/mL for verapamil and trandolapril, respectively. The detection limits were found to be 0.008μg/mL and 0.018μg/mL for verapamil and trandolapril, respectively. Moreover, pKa values of verapamil and trandolapril were determined via the dependence of the retention factor on the pH of the mobile phase for ionizable substances. The effect of the mobile phase composition on the ionization constant was studied by measuring the pKa at different methanol-water mixtures, ranging 50-65% (v/v). It was shown that RP-HPLC was sllitab1e for the high throughput analysis of the combination of verapamil and trandolapril. The method also allows a number of cost and time saving benefits and can be readily employed for the analysis of pharmaceutical formulations. The method has been verified, without any interference from excipients, for the concurrent analysis of these compounds in tablets.

Derivatografic study of the ointment with piroctone olamine for therapy and prevention of seborrheic dermatitis

Пироктон оламин (октопирокс) вместе с выраженным антимикотическим действием обладает широким спектром антибактериальной активности в отношении грам-положительных и грам-отрицательных патогенных микроорганизмов. Октопирокс характеризуется хорошей переносимостью и безвредностью при наружном применении, а также наличием дезодорирующего эффекта. Также перспективным представляется сочетание в рецептуре мази для наружного применения пироктон оламина с нафталаном обессмоленным. Нафталан обессмоленный – натуральное вещество минерального происхождения, обладает десенсибилизирующими, противовоспалительными, обезболивающими, рассасывающими, противозудными, согревающими и антибактериальными свойствами. Сотрудники кафедры технологии лекарств Запорожского государственного медицинского университета на основании комплексных исследований предложили композиционный состав мази с пироктон оламином и нафталаном обессмоленным для топической терапии больных себорейным дерматитом с поражением волосистой части головы. Прогнозируется, что применение разработанного фармакотерапевтического средства будет способствовать нормализации липидной мантии, кератинизации, десквамации, устранению зуда и воспаления пораженных кожных покровов. Цель работы – изучение последствий термообработки комбинационной трихологической мази на гидрофильной основе в интервале температур, сопровождающих технологический процесс производства этой лекарственной формы. Материалы и методы. В качестве объектов дериватографических исследований использовали экспериментальную мазь для местного применения, а также действующие (пироктон оламин, нафталан обессмоленный) и вспомогательные (натрий карбоксиметилцеллюлоза, глицерин, твин 80, пропиленгликоль) вещества этой лекарственной формы. Термогравиметрический анализ проводили с использованием дериватографа «Shimadzu DTG-60» (Япония), снабженного платиново-платинородиевой термопарой. Результаты. Полученные данные термического анализа убедительно свидетельствуют о термической стойкости активных фармацевтических ингредиентов и вспомогательных веществ исследуемой лекарственной формы. На дериватограмах мази с пироктон оламином и ее гидрофильного носителя-плацебо наблюдают совпадение тепловых эффектов с таковыми активно действующего компонента и вспомогательных веществ. Это указывает на отсутствие химического взаимодействия между ними. Выводы. Установлено, что ингредиенты разработанной мягкой лекарственной формы для топической терапии себорейного дерматита с пироктон оламином на гидрофильной основе не взаимодействуют, и потому эта композиция является механической смесью действующих и вспомогательных веществ. Учитывая результаты анализа тепловых эффектов ингредиентов разработанной мази для внешнего применения, целесообразно проведение технологического процесса ее изготовления при температурах, не превышающих 90°С.

Self-assembly of cyclodextrin complexes: detection, obstacles and benefits.

Cyclodextrins (CDs) are cyclic oligosaccharides that form water-soluble inclusion complexes of lipophilic molecules. They are commonly used as pharmaceutical excipients. Recently it has been observed that CDs and CD complexes self-assemble in aqueous solutions to form transient clusters, nanoparticles and small microparticles. The critical aggregation concentration (cac) of the natural αCD, βCD and γCD in pure aqueous solutions is about 25, 8 and 9 mg/ml, respectively. The cac of 2-hydroxypropyl-β-cyclodextrin (HPβCD), that consists of a mixture of isomers, in pure aqueous solutions is significantly higher or about 118 mg/ml. Formation of guest/ CD complexes can increase or decrease the cac value. Due to the transient nature of the CD clusters and nanoparticles they can be difficult to detect and their presence is frequently ignored. However, formation of such particulate matter in aqueous CD solutions can lead to erroneous analytical results and product rejections during drug manufacturing. On the other hand, they have also given rise to formation of novel drug delivery systems with exceptional properties.

A novel HPLC method developed and validated for the detection and quantification of atorvastatin, fluvastatin, pitavastatin and pravastatin during transdermal delivery studies.

An HPLC method was developed and validated to quantify and identify several statins (atorvastatin, fluvastatin, pitavastatin and pravastatin) that were used during transdermal drug delivery. The method proved to be most effective with a Restek Ultra C18, 250 x 4.6 mm, 5 μm column, a flow rate of 1.0 ml/min, UV detection at 240 nm and injection volume of 10 μl. The mobile phase used was acetonitrile/Milli-Q® water with 0.1% orthophosphoric acid starting with 30% acetonitrile, which increased linearly to 70% (after 4 min) for up to 10 min and then re-equilibrated to start conditions. This HPLC method indicated linearity (correlation coefficient (R²) of 1) within the concentration range of 0.05-200.00 μg/ml and had an average recovery of 98-103%. Limit of detection (LOD) and limit of quantification (LOQ) showed that statins could still be identified at concentrations of 0.004-0.006 μg/ml with the exception of atorvastatin (quantifiable at 0.013-0.035 μg/ml). Specificity performed during method validation, confirmed that the method was suitable for accurate detection and quantification of the statins when included in the transdermal formulations with other excipients.

Koruyucu Yardımcı Maddeler Olarak Kullanılan Parabenin Yeni Türevlerinin Sentezi Ve Antimikrobiyal Etkilerinin İncelenmesi

Bu çalışmada paraben bileşiklerinin zararlı etkilerini en aza indirecek alternatif bileşiklerin sentezlenmesi amaçlanmıştır. Paraben bileşiklerinde yer alan grupların değiştirilmesi sonucu, yeni alternatif bileşiklerin sentezi gerçekleştirilerek yapı karakterizasyonları yapılmıştır. İlaçlarda koruyucu yardımcı maddeler olarak kullanılabilecek potansiyele sahip bu sentetik bileşiklerin antimikrobiyal özelliklerinin araştırılması gerçekleştirilmiştir. Bu amaçla çeşitli gram pozitif ve gram negatif bakterilerden Klebsiella pneumoniae ATCC 13883, Escherichia coli ATCC 36218, Bacillus megaterium DSM-32, Staphylococcus aureus ATCC 25923 ve ökaryotik maya olan Candida albicans ATCC10231 ve Yarrowia lipolytica mikroorganizmalarına karşı aktiviteleri incelenmiştir.

Study of excipients influence on the noopept releasing from the nasal dosage form

Разработка средств быстрой доставки лекарственных средств – актуальное направление современной фармации. В связи с этим перспективным является назальный путь введения лекарственных веществ, характеризующийся рядом преимуществ. Большая проницаемость назальной слизистой вместе со значительной площадью поверхности способствует быстрому достижению терапевтического эффекта. Назальный путь минует пресистемный метаболизм в печени, характерный для орального введения, легок в применении и удобен для пациента. Для разработки новой лекарственной формы с ноотропными и нейропротективными свойствами выбран ноопепт. Это вещество малотоксично, не проявляет побочных эффектов, характеризуется проявлениями антиоксидантных и противовоспалительных свойств, снижает проявления нейротоксичности кальция и глутамата, улучшает реологические характеристики крови. Цель работы – определить влияние вспомогательных веществ на высвобождение ноопепта из назальной лекарственной формы. Материалы и методы . Для исследования выбраны основные группы вспомогательных веществ при разработке назальной лекарственной формы: мукоадгезивные и регуляторы вязкости (полимеры) и увлажнители (спирты). Определяли высвобождение ноопепта методом равновесного диализа по Крувчинскому при 37,0 ± 0,5 °С через полупроницаемую мембрану – целлофановую пленку «Купрофан». Концентрацию ноопепта после 30 минут определяли методом УФ-спектрофотометрии при длине волны 258 нм. Результаты . В результате дисперсионного анализа установлено, что F эксперим. > F табл. для обоих факторов, таким образом, полимеры и спирты имеют значимое влияние на высвобождение ноопепта из назальных лекарственных форм. После проверки различия средних значений результатов с помощью множественного рангового критерия Дункана построены следующие ряды преимуществ: натрий карбоксиметилцеллюлоза (хитозан) > альгинат натрия (гиалуронат натрия); глицерин > сорбит > D-пантенол (без спирта). Выводы . Установили, что вид полимеров гидрофильных основ и спирты для увлажнения слизистой значимо влияют на высвобождение ноопета из назальных лекарственных форм. Оптимальное высвобождение ноопепта обеспечивают натрий карбоксиметилцеллюлоза и хитозан с добавлением глицерина.

Compatibility of ticagrelor with pharmaceutical excipients studied with thermal and spectroscopic techniques.

The compatibility between ticagrelor and selected excipients (mannitol, calcium phosphate tribasic, sodium carboxymethyl starch, hydroxypropyl cellulose and magnesium stearate) was investigated by differential scanning calorimetry. The compatibility was further corroborated by Raman spectroscopy and isothermal stress testing experiments. These results revealed that ticagrelor has high compatibility with mannitol, calcium phosphate tribasic, sodium carboxymethyl starch, hydroxypropyl cellulose and magnesium stearate.

Safety of aerosol inhalation of recombinant human interferon alpha 2b injection(P.putida)and excipient hydroxyethyl starch 40 to healthy SD rats

Objective To investigate the effects of recombinant human interferon alpha 2b injection(P.putida)and hydroxyethyl starch inhalation on physiological indexes and tissues and organs of SD rats, such as lungs, trachea and bronchus, and thus to explore the safety of the drug and excipients for inhalation. Methods Rats were randomly divided into two groups(hydroxyethyl starch 40 group and recombinant human interferon alpha 2b group).5 million IU/ml recombinant human interferon alpha 2b injection or 6% hydroxyethyl starch 40 injection were given respectively, which were diluted with 0.9% sodium chloride injection in a radio of 1: 2.Both groups were given aerosol inhalation for 30 minutes once a day for 14 days.Within 14 days after administration, the behavior of rats and the degree of toxicity were continuously observed.During the drug administration and recovery period, the clinical signs of the rats in each group were observed daily, and the body weight and food consumption were measured once a week.At the end of drug administration and the end of recovery period, hematology test, blood biochemical test, gross anatomical observation, organ weight determination, and histopathological examination were performed. Results The mass median aerodynamic diameter(MMAD)of the drug mist was 3.56 μm, and the geometric standard deviation(GSD)was 1.84 μm, which met the particle size requirements of arrival and deposition in the lower respiratory tract via atomization inhalation.No abnormality in clinical signs, body weight and food consumption, hematology and blood biochemical indexes were found in hydroxyethyl starch 40 group and recombinant human interferon alpha 2b group.No abnormal histopathological changes were observed in oral mucosa, tongue, nasal cavity(paranasal sinus), larynx, trachea, main bronchial tube, lung, heart, liver, spleen, kidney, reproductive system and other organs or tissues examined. Conclusion Results suggest the drug particle size of recombinant human interferon alpha 2b injection(pseudomonas)can reach the lower respiratory tract and deposit in the lower respiratory tract.Continuous atomization inhalation for 14 days has a good safety, and the excipient hydroxyethyl starch 40 has a high safety. Key words: Recombinant human interferon alpha 2b; Injection; Aerosol inhalation; Hydroxyethyl starch 40; Safety

Compatibility Between Four Anti-TB Drugs and Tablet Excipients Determined By Microcalorimetry.

Previous isothermal microcalorimetry studies at 40 °C, with and without humidity (RH 75%), had shown no incompatibility between rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA) and ethambutol HCl (EMB). The purpose of this study was to explore any interactions at an increased temperature of 50 °C and also to investigate the possibility of incompatibilities between the drugs and tablet excipients used in the most commonly prescribed commercial four-drug TB FDC. No incompatibilities were observed between the excipients, or when the excipients were tested with the four drugs individually. Incompatibility was observed with the four drugs combined.

Prebiotics as excipients for enhancement of stability and functionality of Bifidobacterium longum ssp. infantis with potential application as symbiotics in food and pharmaceuticals.

Objective: Formulations containing probiotics are promoted due to health benefits. During lyophilization and subsequent storage in the gastrointestinal tract, bacteria are exposed to stress conditions that can lead to impairment and loss of viability. Methods: The suitability of various excipients for enhancing the stability and functionality of Bifidobacterium longum subsp. infantis during storage as freeze-dried powder and through exposure to acid and bile was investigated. Cells were lyophilized in the presence of sucrose, trehalose, lactose, cellobiose and fructooligosaccharide (FOS) and stored at 4 °C or 25 °C. The effect of diverse protectants on the persistence after exposure to acid and bile environment was examined through determination of the colony forming units, the β-glucosidase and β-galactosidase activity and the membrane integrity changes. Results: Cells freeze-dried in the presence of cryoprotectants had comparable survivability during storage at 4 °C whereas the survival rate at 25 °C of cells protected by cellobiose and FOS was higher than for those protected with sucrose and trehalose. Furthermore, the respective excipients used as cryoprotectants enhanced the stability of cells exposed to simulated gastric and small intestinal medium. Stabilization may be achieved through different mechanism of action such as protecting the membrane integrity and as metabolizable substrates. Overall, prebiotic and thus metabolizable protectants including cellobiose and FOS were superior to other protectants used. Conclusion: In symbiotic formulas with B. infantis, these sugars might serve as prebiotics and stabilizers of this probiotic strain during lyophilization, storage and in gastrointestinal conditions simultaneously, potentially increasing its health-promoting effects.

Physicochemical standardization of mucilage obtained from Althaea officinalis Linn – Root

Introduction: Plant derived mucilage has been explored as a drug, pharmaceutical excipient, and in cosmetics. Several mucilage and mucilage-containing drugs are being utilized in Unani medicine. These are to be standardized for authentications owing to immense utilization. A mucilage-containing drug obtained from root of Althaea officinalis L. (AO) – family Malvaceae, an important Unani drug, has been subjected to physicochemical studies for standardization. Materials and Methods: Mucilage of roots of the drug was isolated by classical and reference method. The physicochemical method included determination of ash values, moisture content, viscosity, swelling index (SI), and pH value. Powder characterization study included bulk density, tapped density, Hausner's ratio, and angle of repose. For preliminary phytochemical analysis, qualitative tests for organic constituents and test for mucilage were carried out. Analytical methods, namely Fourier transform infra-red (FTIR) and high-performance thin-layer chromatography (HPTLC) were also applied. Results: The yield percentage taken by acetone method was 36.80 ± 1.25 whereas that of classical method was 42.93 ± 1.35. Values of pH, loss on drying, viscosity, and SI were 4.08 ± 0.032, 14.46 ± 0.13, 34.40 ± 0.61, and 334.36 ± 23.77, respectively. Data for ash value and powder characterization (Micromeritic Properties) were set in. Preliminary confirmative test confirmed that the isolated polysaccharide is mucilage. HPTLC fingerprinting of aqueous extract gave 6 and 4 peak at 254 nm, 4 and 5 peak at 366 nm and 5 and 6 peaks at 550 nm in mobile phase chloroform (90): methanol (10): acetic acid (2). FTIR data for the mucilage were also set in. Conclusion: Physicochemical standardization data/monograph for AO root mucilage were developed.

The Use of Nata de Coco Derived Bacterial Cellulose as a Potential Excipient for Directly Compressed Tablets

Nata de coco is produced through the fermentation of coconut water using Acetobacter xylinum bacteria. Chemically, Nata de coco is high in fiber, consisting of bacterially derived cellulose. Bacterial celluloses present a number of unique physical properties compared with plant celluloses including a relatively high purity and crystallinity, with mechanical strength. These properties lend Nata de coco to be extremely amenable to research. The current study attempts to assess the suitability of Nata de Coco derived bacterial cellulose in direct compression tablet formulation. Nata de coco, at various states of hydration, defined here as 0%, ‘low’ and ‘high’, achieved by both oven-drying and freeze-drying is incorporated into a low-dose loratadine powder blend for direct compression into tablets. The dissolution profile of these novel tablets were evaluated for release properties. The resulting tablets reveal freeze-drying, compared with oven-drying, markedly improve the properties of Nata de Coco for inclusion in a tablet formulation, producing tablets with improved disintegration times and dissolution profiles and retaining physical stability. Oven dried Nata de Coco, resulting in physically weaker tablets, with poor friability and hardness. The upper limit for water-content in both cases, similar to HPMC, appears to be 11%. Freeze-dried Nata de Coco therefore presents considerable promise for use as a tablet excipient to produce a rapid-release formulation.

Compatibility Testing of Nateglinide with Different Grades of Cellulose Ethers and Excipients Used in Sustained Release Formulations

Compatibility testing was done to assess interaction between Nateglinide (NTG) and different pharmaceutical excipients and polymers, which are used in a sustained release formulation to manufacture tablet. To evaluate the compatibility between drug, excipients and polymers, different techniques such as Differential Scanning Calorimetry (DSC), Infrared Spectroscopic study (IR) and Isothermal stress testing (IST) study were employed. The results of DSC curves showed that, all excipients and polymers are compatible with the NTG. Except DSC curves of magnesium stearate, which shows certain interaction with the NTG, however, it overcome in the results of IR and IST studies, which showed that all the excipients, polymers used in this study are compatible with the NTG.

Revance's novel peptide excipient, RTP004, and its role in stabilizing daxibotulinumtoxinA (DAXI) against aggregation

Revance's novel peptide excipient, RTP004, and its role in stabilizing daxibotulinumtoxinA (DAXI) against aggregation