Market Formulation Research Articles

Development and Validation of UV-Spectrophotometric Method for The Estimation of Felbinac In Marketed Formulation and Cubosomal Nano Formulation.

Development and Validation of UV-Spectrophotometric Method for The Estimation of Felbinac In Marketed Formulation and Cubosomal Nano Formulation.

Sustainable and Green Fluorescence Method for the Determination of Cloperastine in Human Plasma: Greenness Assessment.

A newly green method for the sensitive quantification of cloperastine, a cough suppressant, in spiked human plasma and its pharmaceutical formulation was designed for the first time. The established method depends on the enhancement of the weak fluorescence of cloperastine using 50 mM sulfuric acid to impair the photoinduced electron transfer produced from the nitrogen atom of piperidine moiety in cloperastine. This full protonation in an acid medium leads to an enhancement in the fluorescence of cloperastine, permitting its linear determination from 0.2 to 5.0µg/mL with LOD and LOQ of 0.04 and 0.13µg/mL, respectively. Moreover, the studied drug was estimated in its pharmaceutical market formulations as well as spiked human plasma. Furthermore, the greenness of the described method was evaluated.

Phytochemistry, Pharmacological Actions and Market Formulations of Sea buckthorn (Hippophae rhamnoides L.): A Comprehensive Review

Phytochemistry, Pharmacological Actions and Market Formulations of Sea buckthorn (Hippophae rhamnoides L.): A Comprehensive Review

Isolation and Quantification of Scopoletin from Leaves and Marketed Formulation of Morinda Citrifolia L.

Isolation and Quantification of Scopoletin from Leaves and Marketed Formulation of Morinda Citrifolia L.

Peer-to-peer multi-period energy market with flexible scheduling on a scalable and cost-effective blockchain

Peer-to-Peer (P2P) electricity trading is an emerging means for allowing communities to share local energy production and demand response through direct trading. It is projected to play an important role in the future energy market by increasing the incentive to own and operate distributed energy resources (DERs) and participate in demand response (DR). A common approach to implementing P2P trading is with blockchain, however, existing solutions feature limitations. Typically, concerns involve either scalability and high transaction costs or projects implementing a permissioned blockchain that does not provide the trust and decentralization desired. In addition, the majority of market designs are simplified and do not capture the distinct complexity of electricity markets. They do not consider the inter-temporal constraints of appliances and DERs that need to run for multiple periods. Complex market designs that address these issues have not been implemented in blockchain based systems due to the computational limitations of such systems. To improve these two aspects, this paper proposes a market formulation that supports products running multiple periods with flexible scheduling, modeled as a mixed integer linear programming problem that optimizes social welfare. The trading platform is then implemented as a side chain of Polkadot, a network of blockchains designed to be secure, scalable, and economically feasible to foster an ecosystem of application-specific sidechains. This design is demonstrated to improve social welfare and achieve scalability by benchmarking the number of transactions that can be included per second, based upon typical assumptions of the market size. The result is a decentralized and performant system that allows for complex market designs to be implemented in a blockchain environment. This approach simplifies the process for participants, allowing them to bid DER or DR devices, directly and easily, even when this requires constraints across periods.

Co-Delivery of Aceclofenac and Methotrexate Nanoparticles Presents an Effective Treatment for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a common acute inflammatory autoimmune connective tissue arthropathy. The genetic studies, tissue analyses, experimental animal models, and clinical investigations have confirmed that stromal tissue damage and pathology driven by RA mounts the chronic inflammation and dysregulated immune events. We developed methotrexate (MTX)-loaded lipid-polymer hybrid nanoparticles (MTX-LPHNPs) and aceclofenac (ACE)-loaded nanostructured lipid carriers (ACE-NLCs) for the efficient co-delivery of MTX and ACE via intravenous and transdermal routes, respectively. Bio-assays were performed using ex-vivo skin permeation and transport, macrophage model of inflammation (MMI) (LPS-stimulated THP-1 macrophages), Wistar rats with experimental RA (induction of arthritis with Complete Freund's adjuvant; CFA and BCG), and programmed death of RA affected cells. In addition, gene transcription profiling and serum estimation of inflammatory, signaling, and cell death markers were performed on the blood samples collected from patients with RA. Higher permeation of ACE-NLCs/CE across skin layers confirming the greater "therapeutic index" of ACE. The systemic delivery of MTX-loaded LPHNPs via the parenteral (intravenous) route is shown to modulate the RA-induced inflammation and other immune events. The regulated immunological and signaling pathway(s) influence the immunological axis to program the death of inflamed cells in the MMI and the animals with the experimental RA. Our data suggested the CD40-mediated and Akt1 controlled cell death along with the inhibited autophagy in vitro. Moreover, the ex vivo gene transcription profiling in drug-treated PBMCs and serum analysis of immune/signalling markers confirmed the therapeutic role co-delivery of drug nanoparticles to treat RA. The animals with experimental RA receiving drug treatment were shown to regain the structure of paw bones and joints similar to the control and were comparable with the market formulations. Our findings confirmed the use of co-delivery of drug nanoformulations as the "combination drug regimen" to treat RA.

Quantification of ternary mixture of paracetamol, chlorzoxazone and ibuprofen present in tablet dosage form using ratio subtraction spectrophotometric approaches

A sensitive and selective spectrophotometric approach comprising of successive ratio subtraction was developed for quantification and resolution of spectrum of mixture containing three components without prior separation. Three components, namely paracetamol, chlorzoxazone and ibuprofen were present in tablet dosage form. The linearity studies were carried out by recording zero order spectra and measuring absorbances at 285.0, 282.0 and 220.0 nm for paracetamol, chlorzoxazone and ibuprofen respectively. The drugs exhibited linear response in the concentration range of 6.0–18.0, 3.0–15.0 and 4.0–20.0 µg / mL for paracetamol, chlorzoxazone and ibuprofen respectively. The spectrum of paracetamol was most extended which was subsequently followed by moderately extended spectrum of chlorzoxazone and unextended spectrum of ibuprofen. The ratio spectra were manipulated successfully for quantification of paracetamol, chlorzoxazone, and ibuprofen. The developed method was validated as per ICH guidelines for the parameters of specificity, linearity, precision and accuracy. The percent recoveries for all the three drugs were in the range of 98.0–102.0 % with mean recovery of paracetamol, chlorzoxazone and ibuprofen were 99.72, 99.02 and 100.34 % respectively. Additionally the validity of the method is assured by analyzing marketed formulation.

Preparation and Evaluation of Classical Ayurvedic Formulation Triphala gritha

Objective The objective of this study was to prepare and evaluate Triphala gritha.Methods The selected formulation Triphala ghrita was prepared as per the methodology described in Ayurvedic texts. The prepared and marketed formulations were analyzed for their physico-chemical constants using established methods in accordance with WHO guidelines the Indian Pharmacopoeia and standard protocols from the Ayurvedic Pharmacopoeia of India Herbal Pharmacopoeia and other relevant sources.Results A profile consisting of distinguishing parameters was developed to provide means of correct identification. Some important organoleptic features of Triphala ghrita laboratory and market formulations like color odour taste appearance touch etc. were documented. Physico-chemical constants were determined and documented. The formulations were tested for the presence of heavy metals microbial content pesticide residues and aflatoxin which were also found within the limits of WHO specifications. Preliminary phytochemical studies of Triphala ghrita revealed the presence of terpenoids and phenolics as chief constituents. High performance thin-layer chromatography HPTLC method was developed and reported for the quantification of ascorbic acid and gallic acid as marker constituents to ensure identity and quality of Triphala ghrita.Conclusion The studies carried out on Triphala ghrita can serve as a valuable tool and provide suitable standards for its identification. Phytochemical screening and the quantitative HPTLC assay method developed for quantification of ascorbic acid and gallic acid in Triphala ghrita can serve for the routine quality control of commercial samples and help in justifying the traditional claims endowed upon this formulation in a scientifically accepted manner.

Fermented formulation of Silybum marianum seeds: Optimization, heavy metal analysis, and hepatoprotective assessment

BackgroundFermented formulations are extensively used in Ayurveda due to several benefits like improved palatability, bioavailability, pharmacological potential, and shelf life. These formulations can also quench the heavy metals from the plant material and thus reduce the toxicity. Seeds of Silybum marianum (L.) Gaertn. are widely used for the management of many liver diseases. Study design and methodsIn the present study, we developed a novel fermented formulation of S. marianum seeds and evaluated parameters like safety (heavy metal analysis) and effectiveness (hepatoprotective). As the developed formulation's validation is crucial, the critical process variables (time, pH, and sugar concentration) are optimized for alcohol and silybin content using the Box-Behnken design (BBD). ResultsThe response surface methodology coupled with BBD predicted the optimized conditions (fermentation time (28 days), pH 5.6, and sugar concentration (22.04%)) for the development of a fermented formulation of the selected herb. Moreover, the alcohol content (6.5 ± 0.9%) and silybin concentration (26.1 ± 2.1%) were confirmed in optimized formulation by GC–MS and HPTLC analysis. The optimized formulation was also analyzed for heavy metals (Pb, As, Hg, and Cd); their concentration is significantly less than the decoction of herbs. Further, the comparative evaluation of the developed formulation with the marketed formulation also confirmed that the fermented formulation's silybin concentration and percentage release were significantly enhanced. In addition, the developed fermented formulation's percentage recovery of HepG2 cell lines after treatment with CCl4 was significantly improved compared with the marketed formulation. ConclusionIt can be summarized that the developed fermented formulation improves safety and effectiveness compared to other market formulations. Finally, it can be concluded that the developed fermented formulation could be further explored as a better alternative for developing Silybum marianum preparation.

Estimation of Andrographolide Content in Aqueous and Methanolic Extracts of Marketed Nilavembu Kudineer Siddha formulations by HPTLC Technique

Andrographis paniculata is one of the important ingredient used in various Siddha formulations. The present study is mainly aimed to compare various marketed nilavembukudineer churna on the basis of andrographolide content. HPTLC method was used for this determination using marker compound andrographolide. The HPTLC method was performed using HPTLC aluminium sheets precoated with silica gel 60 GF254 as stationary phase and ethyl acetate: n-hexane (8.5:1.5 v/v) as the mobile phase. The developed chromatogram was scanned at 233nm using Camag scanner III. The reference standard andrographolide Rf value was found to be 0.55.Fromthe five market formulations screened, the andrographolide content in methanolic and aqueous extracts showed the discrepancy in content amount representing by order MFM-1 MFA-1 MFM-2 MFA-2 -3.The other market formulation extracts both methanol and aqueous extracts does not confirms the presence of andrographolide.

Simultaneous Estimation of Berberine and Quercetin in Pathydi Kada Formulation by Hptlc

A sensitive, selective and precise thin-layer chromatographic method has been developed and validated for the analysis of Berberine and Quercetin in Pathydi Kada laboratory prepared and Market formulation. Separation and quantification were achieved by TLC using mobile phase of Ethyl acetate: Methanol: Glacial acetic acid (6: 4: 0.5) v/v/v (Rf 0.2 & 0.84 for Berberine and Quercetin respectively) on precoated silica gel 60F254 aluminum plates and determination was carried out at 254 and 366 nm for berberine and quercetin respectively. The calibration curve was linear in the concentration range of 4-12 μg spot-1. The method was validated for precision, repeatability and accuracy. The proposed method was found to be simple, precise, specific, sensitive and accurate for the quantification of Berberine and Quercetin. This is the first TLC report for the simultaneous estimation of Berberine and Quercetin in Pathydi Kada formulation and may be useful for the routine quality control.

Design of Mouth Dissolving Polyherbal Films for Dental Caries

Oral disease is still a major public health problem across the globe in developed countries as well as developing countries. Dental caries is one of humans’ oldest and most prevalent diseases or conditions of factor situations. The present study was designed to evaluate the antimicrobial potential of polyherbal film containing extracts of Annona squamosa L, Mentha piperita and Acalypha indica leaves against Streptococcus mutans. The mouth-dissolving poly herbal films were formulated with 1% (OF1), 2% (OF2) and 3% (OF3) extract concentrations. OF3 produced better results than OF1 and OF2 in folding endurance, disintegration time and dissolution time. The antimicrobial properties of the polyherbal films and standard marketed formulations S1 and S2 mouthwash were evaluated against the dental pathogen, S. mutans. OF3 produced a zone of inhibition 18.3 ± 0.21 mm compared to S2 which produced an inhibition zone of 27.0 ± 0.24 mm, whereas S1 has not shown any zone of inhibition. These results indicated that the mouth dissolving poly herbal films could be effective in the treatment of dental caries and gingivitis.

Possibilities and limitations of α-relaxation data of amorphous freeze-dried cakes to predict long term IgG1 antibody stability

The value of correlating global α-relaxations with long term protein stability after freeze-drying is inconsistently reported. This study aims to clarify whether and to what extend the long term stability of a freeze-dried protein formulation can be predicted with this method. For this purpose, the α-relaxation parameter τβ [h] of freshly prepared freeze-dried products is obtained by isothermal microcalorimetry. The concept is, that molecular movements in the amorphous matrix are strongly reduced in cakes with longer relaxation time and the product should therefore be more resistant against aggregation. To increase τβ in comparison to a conventional freeze-drying cycle, aggressive drying cycles including structural collapse of the product as well as tempering protocols after freeze-drying are applied. The τβ values are correlated with the aggregation rate of a freeze-dried IgG1 monoclonal antibody measured with high performance size exclusion chromatography. The antibody was used in its market formulation and 6 further compositions. A weak correlation between α-relaxation times and IgG1 aggregation was found. A higher mobility level through increased residual moisture helped to improve the correlation.

An Auction Pricing Model for Energy Trading in Electric Vehicle Networks

In recent years, the interest in electric vehicles (EVs) in the research community has been growing, particularly in the context of decarbonization. Additionally, there is a growing increase in their number, leading to massive energy demand on the charging stations (CSs). Energy trading management for CSs puts great pressure on the power grid and is a stimulating challenge in smart cities. In this paper, we propose an innovative market formulation in which autonomous vehicles and smart charging and discharging stations are motivated to cooperate dynamically with changing roles. In order to mathematically formulate the energy trading market, we adopt a double auction strategy that is repeated in steps. In this strategy, EVs and CSs participate by buying and selling energy. The investigated problem has high complexity, and thus, multi-objective optimization is employed so as to encapsulate the opposing objectives that the EVs and CSs have. Multi-objective optimization leads to a fairer and more efficient market operation. The performance of the presented approach is investigated through analytical and experimental results. More specifically, the proposed algorithm achieves up to 52.5% reduction in energy consumption. The performance evaluation proves that the suggested strategy offers both fairness and significant energy benefits, encouraging both electric vehicles and charging stations to take part in a double auction energy trading system.

Simultaneous identification and quantification of pentacyclic triterpenoids and phenolic compounds from the leaves of Boswellia serrata using LC-MS/MS tandem mass spectrometry.

Boswellia serrata (B. serrata) is an important medicinal plant widely used as dietary supplements to provide a support for osteoarthritic and inflammatory diseases. The occurrence of triterpenes in leaves of B. serrata is very little or none. Therefore, the qualitative and quantitative determination of phytoconstituents (triterpenes and phenolics) present in the leaves of B. serrata is very much needed. The aim of this study was to develop an easy, rapid, efficient and simultaneous liquid chromatography-mass spectrometry (LC-MS/MS) method for the identification and quantification of the compounds present in the leaves extract of B. serrata. The purification of ethyl acetate extracts of B. serrata was performed by solid phase extraction method, followed by HPLC-ESI-MS/MS analysis. Chromatographic parameters of the analytical method included negative electrospray ionization (ESI-) with a flow of 0.5mL/min in gradient mode consisting of acetonitrile (A) and water (B) containing 0.1% formic acid, at 20°C. Total 19 compounds (13 triterpenes and 6 phenolic compounds) were separated, and simultaneously quantified using a validated LC-MS/MS method with high accuracy and sensitivity. Good linearity was obtained with r2 > 0.973 in the calibration range. The overall recoveries were in a range between 95.78 and 100.2% with relative standard deviations (RSD) below 5% for the entire procedure of matrix spiking experiments. Overall, there was no ion suppression from the matrix. The quantification data showed that the total amount of triterpenes and phenolic compounds in the leaves of B. serrataethyl acetate extract samples ranged from 14.54 to 102.14mg/g and 2.14 to 93.12mg/g of dry extract, respectively. This work provides, for the first time, a chromatographic fingerprinting analysis on the leaves of B. serrata. A rapid, efficient, and simultaneous liquid chromatography-mass spectrometry (LC-MS/MS) method was developed and used for the both identification and quantification of triterpenes and phenolic compounds in the leaves extracts of B. serrata. The method established in this work can be used as quality-control method for other market formulations or dietary supplements containing leaf extract of B. serrata.

Comparative in Vivo Study on Quality Analysis on Bisacodyl of Different Brands

Abstract: Bisacodyl is an organic chemical belongs to the diphenylmethane family that is utilised as a laxative stimulant. To induce a bowel movement, it acts directly on the colon. It is commonly used to treat episodic and chronic constipation, as well as neurogenic bowel dysfunction, and as part of bowel preparation before medical procedures such as a colonoscopy. It has a dual prokinetic and secretory activity and must be converted in the stomach into the active metabolite bis-( p-hydroxyphenyl)-pyridyl2-methane (BHPM) to generate the intended laxative effect. Bisacodyl operates locally in the large bowel by directly improving motility, decreasing transit time, and raising stool water content. The tablets available on the market from various popular brands were chosen for the evaluation based on different quality control tests such as physical appearance, hardness, friability, disintegration time, weight variations, dissolution rate, and potency. The test will be implement of the certain kind of available product such as DULCOFLEX, BISOWEX, BISFLOW and BYLAX-5 which has active contain of 10mg/each respectively. This study is likely to be a point of appreciation in raising awareness among the people and prescriber communities about the importance of having a higher surplus of medicines by selecting the suitable medication from among some sorts of commercial brands which is available in market formulation.

Drug-Excipient Compatibility Study Through a Novel Vial-in-Vial Experimental Setup: A Benchmark Study.

Drug-excipient compatibility study (DECS) is one of the critical steps during pre-formulation studies to select the appropriate excipient to obtain a stable formulation/dosage form. As such, there is no recommended guideline for DECS. Further, the previously reported studies and protocols followed by various pharmaceutical industries are very lengthy and laborious. Therefore, to improve the existing study strategies and rapid screening of suitable excipients during formulation development, a novel vial-in-vial approach has been proposed. The devised approach was compared with the previously reported conventional approaches using six different drugs with multiple marketed formulations from different manufacturers for each drug. To validate the proposed novel approach, several reported strategies/methodologies have been executed such as exposure of formulations with and without primary packaging, crushed blend with and without water, and/or acetonitrile at accelerated stability condition of 40°C/75% RH for 3 to 6months and compared with the novel approach. Eventually, all the samples were subjected to HPLC analysis to evaluate the degradation behaviour. The results suggested that the novel approach demonstrated discriminating results with significant degradation as compared to the conventional approaches. Consequently, exercising this methodology for screening the excipients is expected to shorten the drug development cycle by many folds. Moreover, it has also been anticipated that the developed novel approach would prevent the occurrence of late-stage surprises during stability studies.

Green easily implemented spectrophotometric methods for concurrent determination of ephedrine hydrochloride and naphazoline nitrate in nasal preparations containing methylparaben.

Spectrophotometric resolution of a mixture of several drugs is considered a cheaper, simpler and more versatile alternate compared to the costly chromatographic instruments. The work aims to resolve the interfering spectra of ephedrine hydrochloride, naphazoline nitrate and methylparaben in nasal preparations using smart spectrophotometric methods. In our work, derivative and dual wavelength methods were combined to eliminate this interference, under the name of derivative dual wavelength method. Other methods, namely successive derivative subtraction and chemometric analysis were also able to eliminate this interference. The methods have proven their applicability as they follow the ICH requirements regarding repeatability, precision, accuracy, selectivity, and linearity. Eco- scale, GAPI and AGREE tools were used to estimate the possible environmental effects of the methods. Acceptable results of repeatability, precision, accuracy, selectivity, and linearity were obtained. LOD values were 2.2 for ephedrine and 0.3 for naphazoline. The correlation coefficients were above 0.999. The methods were proven to be safe for application. The introduced methods are cheap and easily implemented compared to chromatographic techniques. They can be used in purity checking of raw material and estimation of concentrations in market formulations. The replacement of the published chromatographic techniques with our developed methods is usefulwhen saving money, effort and time is needed. The three components of a decongestant nasal preparation were determined using cheap green versatile spectrophotometric methods that keep the advantages of chromatographic techniques including accuracy, reproducibility and selectivity.

Bilateral Peer-to-Peer Energy Trading via Coalitional Games

In this paper, we propose a bilateral peer-to-peer (P2P) energy trading scheme under single-contract and multi-contract market setups, both as an assignment game, a special class of coalitional games. The proposed market formulation allows for efficient computation of a market equilibrium while keeping the desired economic properties offered by the coalitional games. Furthermore, our market model allows buyers to have heterogeneous preferences (product differentiation) over the energy sellers, which can be economic, social, or environmental. To address the problem of scalability in coalitional games, we design a novel distributed negotiation mechanism that utilizes the geometric structure of the equilibrium solution to improve the convergence speed. Our algorithm enables market participants (prosumers) to reach a consensus on a set of “stable” and “fair” bilateral contracts which encourages prosumer participation. The negotiation process is executed with virtually minimal information requirements on a time-varying communication network that in turn preserves privacy. We use operator-theoretic tools to rigorously prove its convergence. Numerical simulations illustrate the benefits of our negotiation protocol and show that the average execution time of a negotiation step is much faster than the benchmark.

CCD based Development and Characterization of Tranexamic acid Loaded Transethosomes for Melasma

This study was intended to develop and optimize Tranexamic acid (TXA) loaded transethosomal (TEL’s) patch for the treatment of melasma. Upon oral administration, TXA is reported to cause gastrointestinal (GI) sideeffects and showed 30-50% bioavailability. Hence an alternative transdermal drug delivery system has been designed in the form of transethosomes (TEL). TXA loaded TELwere prepared by the cold method using Phospholipon 90G as a lipoid, sodium cholate as an edge activator, ethanol, and water. Further size reduction was done using a probe sonicator. For optimization purposes central composite design (CCD) was used. Phospholipon 90G and sodium cholate were selected as independent variables. Particle size (PS) and entrapment efficiency (E.E) were selected as a response. Mathematical equations and 3-D response surface graphs were used to relate dependant and independent variables. The optimized model pre-predicted and experimentally gave the particle size of 72nm, zeta potential of -16mV, encapsulation efficiency of 94%, with an enhanced transdermal flux of 32.85μg/cm2 /h as compared to a conventional topical cream. In vitro and ex-vivo studies were done to check the efficacy of the formulation and the results showed improved release of drug in TEL formulation as compared to conventional marketed formulation.