Formulation Factors Research Articles

Enhanced Anti-inflammatory Effects of Diclofenac Delivered Orally via Polyvinylpyrrolidone K30/Silk Fibroin Nanoparticles in a Murine Model of Carrageenan-Induced Paw Edema.

Diclofenac has a relatively low oral bioavailability (50-60%) and is quickly metabolized with a half-life of less than 1 h. Therefore, the oral therapeutic effect of diclofenac is not optimal. This research developed polyvinylpyrrolidone K30-functionalized silk fibroin nanoparticles as an effective delivery system for diclofenac (FNPs-PVP-DC). The FNPs-DC and FNPs-PVP-DC were formulated by two methods of adsorption and solvent exchange. Depending on the formulation factors, the obtained particles exhibited different properties of nano-scale sizes (400-800 nm), narrow size distribution, negatively charged surfaces (-17 to -19 mV), high PVP K30 incorporation (23%-50%), pHpzc of ~6.6, and appropriate chemical interactions. Interestingly, particles formulated by the adsorption method showed low drug encapsulation efficiencies of < 15%, whereas the solvent exchange method yielded moderate results of ~40%. The FNPs-DC possessed aggregated patterns, while the FNPs-PVP-DC were more uniformly distributed. All formulations limited diclofenac release (< 20%) under gastric conditions and sustained its release in the intestinal environment. In in-vivo carrageenan-induced paw edema mice model, the FNPs-PVP-DC demonstrated a 20-30% higher anti-inflammatory effect and a faster onset of action (within 1 h) compared to pure diclofenac at the same dose (5 mg/kg). These findings suggest that FNPs-PVP-DC have promising potential as novel oral anti-inflammatory products.

Application of high-polarity hydroxyl polyacrylate pressure sensitive adhesive in rizatriptan transdermal drug delivery patch

This study aimed to design a rizatriptan (RIZ) transdermal patch by combining of high-polarity hydroxyl pressure sensitive adhesive (PSA) AAOH-45 with an ion-pair strategy and investigate the molecular mechanism of high content hydroxyl PSA to enhance drug-PSA miscibility. RIZ free base, ion-pair complexes and PSAs containing hydroxyl group were prepared and characterized. Formulation factors including counter-ions, PSAs, drug-loading and others were optimized through single-factor studies and evaluated through pharmacokinetic studies and skin irritation tests. The properties of high polarity PSA and molecular mechanism of drug-PSA miscibility were investigated through molecular simulation, FTIR spectra, 13C NMR spectra, DSC, and rheology study. The optimized formulation contained 20 % (w/w) RIZ-OA (Rizatriptan-Oleic acid), 80 % AAOH-45 (w/w) as the matrix, and had a thickness of 90 μm. Compared with the oral group (MRT0-t = 5.96 ± 0.97 h) and the control patch group (MRT0-t = 11.30 ± 1.78 h), the pharmacokinetic behavior of the optimization group demonstrated sustained drug delivery behavior (MRT0-t = 20.21 ± 0.61 h) with no irritation phenomenon. The miscibility of RIZ with PSAs was positively correlated with the mass percentage of 2-HEA. Higher polar similarity, lower flowability, and stronger intermolecular interaction were responsible for the higher compatibility of high hydroxyl PSA with the drug. This study provided a reference for increasing the drug-loading in PSA and developing RIZ patch.

Data-driven insights into the properties of liquisolid systems based on machine learning algorithms

Liquisolid systems (LS) represent a formulation approach where liquid drug or its dispersion is transformed into a powder with good flowability and compactibility, leading to enhanced drug dissolution and bioavailability. Many research groups have focused on the preparation and investigation of LS, leading to a higher need for comprehensive evaluation of factors impacting LS characteristics. The aim of this work was to investigate the applicability of machine learning algorithms in the LS evaluation, using data mined from published literature, and provide an insight into critical factors governing the liquisolid system performance.The dataset was prepared using publication search engines and relevant keywords, with a total of 425 formulations included in the database. The database focused on preparation methods, formulation parameters, and liquisolid system characteristics. Subsequently, critical properties of the liquisolid system, i.e. flowability, compact hardness, and drug dissolution, were analyzed using machine learning algorithms, including Gradient Boosting, Adaptive Boosting and Random Forest.In addition to conventional preparation methods and excipients, novel technologies (fluid bed preparation, extrusion/spheronization) and materials (Neusilin®, Fujicalin®, and Syloid®) enhanced the properties of liquisolid systems. The analysis revealed that formulation factors, such as carrier and coating agent type and content, liquid phase load, model drug type and content, as well as preparation method, significantly influenced liquisolid system characteristics. The models developed exhibited high prediction accuracy when applied on test data (higher than 80 %). This indicates that the machine learning models may provide an insight into the critical attributes affecting the LS performance and may be used as a valuable tool in the development and optimization of these samples.

REVIEW : OF SUPERDISINTEGRANT INGREDIENTS IN FAST DISINTEGRANT TABLET TABLET PREPARATIONS

This study aimed to evaluate the potential of synthetic and natural disintegrating agents in fast-disintegrating tablet (FDT) formulations. The methodology used includes a comprehensive literature review on the definition, characteristics, working mechanisms, and applications of super disintegrants in the manufacture of FDTs. The results of the study showed that super disintegrants play an important role in facilitating rapid disintegration of tablets. Synthetic super disintegrants such as crospovidone, croscarmellose sodium, and sodium starch glycolate have the advantage of lower concentrations and better intragranular effectiveness. On the other hand, natural superdisintegrants such as mucilages, gums, and polysaccharides from plants have easy availability, affordable prices, non-toxic properties, and biologically acceptable characteristics. In conclusion, the selection of an appropriate super disintegrant, whether synthetic or natural, is a key factor in effective FDT formulation and providing rapid disintegration. The combination of using super disintegrants at the granulation stage (intragranular) and before compression (extragranular) can produce better performance compared to a single method. Keywords: FDT, Super disintegrant, Synthetic, Natural

Advancing Pharmaceutical Science with Artificial Neural Networks: A Review on Optimizing Drug Delivery Systems Formulation.

Drug Delivery Systems (DDS) have been developed to address the challenges associated with traditional drug delivery methods. These DDS aim to improve drug administration, enhance patient compliance, reduce side effects, and optimize target therapy. To achieve these goals, it is crucial to design DDS with optimal performance characteristics. The final properties of a DDS are determined by several factors that go into formulating a pharmaceutical preparation. Thus, optimizing these factors can lead to the ideal DDS formulation. Artificial Neural Networks (ANN) are computational models that mimic the function of biological neurons and neural networks and perform mathematical operations on inputs to generate outputs. ANN is widely used in medical sciences for modeling disease diagnosis and treatment, dose adjustment in combination therapy, medical education, and other fields. In the pharmaceutical sciences, ANN has gained significant attention for designing and optimizing pharmaceutical formulations. This article reviews the use of ANN in the design and optimization of pharmaceutical formulations, specifically DDS. Since DDS is highly diverse, different factors are examined for each type of DDS. These factors are considered independent and dependent parameters for each ANN model, and various examples are provided. By utilizing ANN, it is possible to establish the relationship between the formulation factors and the resulting DDS characteristics, ultimately leading to the development of optimized DDS.

Recent Advances in Orally Disintegrating Tablet: Properties, Formulation and Production

: Healthcare practitioners, patients, and consumers widely recognize the convenience as-sociated with administering oral tablets. The emergence of orally disintegrating tablets (ODTs) represents a significant advancement in solid dosage forms, facilitating more convenient oral de-livery while maintaining medication safety, effectiveness, and quality. The ODTs market is ex-pected to experience continuous growth in the coming years despite the internal challenges faced by commercial manufacturers. This paper initiates a comprehensive discussion of the properties of ODTs, including palatability and taste, drug content, disintegration, mechanical strength, mois-ture content, safety, and efficacy. The formulation factors that affect each of these qualities are also discussed. Additionally, this review delves into the processes of the production of ODTs, en-compassing the approaches and technologies from the mixing of active ingredients and recipients to the formation and packaging of ODTs. This review provides valuable insights into the ad-vancement in ODTs technology, aiming to equip researchers with the knowledge necessary to improve quality and optimize efficiency, ultimately receiving high acceptance from patients or consumers.

Effect of processing and formulation factors on Catalase activity in tablets

The manufacturing of tablets containing biologics exposes the biologics to thermal and shear stresses, which are likely to induce structural changes (e.g., aggregation and denaturation), leading to the loss of their activity. Saccharides often act as stabilizers of proteins in formulations, yet their stabilizing ability throughout solid oral dosage processing, such as tableting, has been barely studied. This work aimed to investigate the effects of formulation and process (tableting and spray-drying) variables on catalase tablets containing dextran, mannitol, and trehalose as potential stabilizers. Non-spray-dried and spray-dried formulations were prepared and tableted (100, 200, and 400 MPa). The enzymatic activity, number of aggregates, reflecting protein aggregation and structure modifications were studied. A principal component analysis was performed to reveal underlying correlations. It was found that tableting and spray-drying had a notable negative effect on the activity and number of aggregates formed in catalase formulations. Overall, dextran and mannitol failed to preserve the catalase activity in any unit operation studied. On the other hand, trehalose was found to preserve the activity during spray-drying but not necessarily during tableting. The study demonstrated that formulation and process variables must be considered and optimized together to preserve the characteristics of catalase throughout processing.

A glance into factors affecting the possible combined entrapment of curcumin and methylene blue into niosomal formulations as a potential anticancer therapy

Niosomes are non-ionic surfactant vesicles that has successfully attracted a great deal of attention over the last few decades. The best ratio between main components is the key to creating the optimum formulations with substantial loading capacity. Therefore, this study investigated formulation factors that could affect the entrapment of two compounds with different solubilities, namely Methylene blue (MB) and curcumin (CUR) as model hydrophilic and hydrophobic compounds, respectively. The aim was to propose an optimum formula to encapsulate both compounds as a potential hybrid anticancer therapy. The factors with potential influence on the entrapment efficiency (EE) included the type of the non-ionic surfactants (Span 60 versus Span 65), cholesterol to surfactant ratio, and the concentrations of the co-surfactant (Cremophor RH40). Niosomes were prepared by thin film hydration technique and downsized using probe sonicator. The morphology, vesicle size and polydispersity index (PDI) of the prepared vesicles were inspected. The data showed the superiority of Span 65 over Span 60 in terms of higher encapsulation efficiency for MB and CUR. The results reflected positive impact of cholesterol and Cremophor RH40 concentration on EE of the two compounds. The optimum composition of Span 65:cholesterol:Ccremophor RH40 was at the mol% ratio of 45:45:10, respectively, with EE of 91.19 % for CUR alone, 51.70 % for MB alone, and 45.32 %/84.40 % for combined MB/CUR loaded formulations. The vesicle size of the formulations after probe sonication, fall into the range of 100–200 nm, ideal for parenteral delivery to the target sites.

Investigation of the effect of different formulation factors on the shelf life of Vitamin C in aqueous solutions

Vitamin C (Vit C)is sensitive to oxidation therefore, the preparations containing Vit C should assure its stability. The aim of this research was to stabilize Vit C in aqueous solutions containing viscosity-increasing agent (HPMC or chitosan) by modifying HPMC concentration or by solvents addition of different polarities and viscosities (eg. glycerin or alcohol). Solutions were characterized for appearance, pH, spreadability and stability. Kinetic of Vit C degradation was estimated by determining reaction orders, rate constants and shelf lives (t90). The results showed that t90 enhanced when glycerin and alcohol were added in solutions. Viscosity and low water activity enhanced Vit C stability (when glycerin increased). Chitosan had a positive effect on stability as it prolonged the shelf life of Vit C to almost 40days.

Comparison of elements and state-variable transfer methods for quasi-incompressible material behaviour in the particle finite element method

AbstractThe Particle Finite Element Method (PFEM) is attractive for the simulation of large deformation problems, e.g. in free-surface fluid flows, fluid–structure interaction and in solid mechanics for geotechnical engineering and production processes. During cutting, forming or melting of metal, quasi-incompressible material behaviour is often considered. To circumvent the associated volumetric locking in finite element simulations, different approaches have been proposed in the literature and a stabilised low-order mixed formulation (P1P1) is state-of-the-art. The present paper compares the established mixed formulation with a higher order pure displacement element (TRI6) under 2d plane strain conditions. The TRI6 element requires specialized handling, involving the deletion and re-addition of edge-mid-nodes during triangulation remeshing. The robustness of both element formulations is analysed along with different state-variable transfer schemes, which are not yet widely discussed in the literature. The influence of the stabilisation factor in the P1P1 element formulation is investigated, and an equation linking this factor to the Poisson ratio for hyperelastic materials is proposed.

Photoinitiators for Medical Applications-The Latest Advances.

Photopolymerization is becoming increasingly popular in industry due to its copious advantages. The vital factor in the entire pre-polymerization formulation is the presence of photoinitiators. Depending on the application, photoinitiators have different features. Hence, scientists are particularly interested in developing new photoinitiators that can expand the scope of applications and be used to create products with the features demanded by current trends. This brief review summarizes the photoinitiators used in dental materials and hydrogels and those obtained from natural and synthetic sources.

QbD Approach in Cosmetic Cleansers Research: The Development of a Moisturizing Cleansing Foam Focusing on Thickener, Surfactants, and Polyols Content.

Cleansing products, particularly innovative cosmetic foams, must efficiently remove impurities with minimal impact on the skin barrier and have a favorable sensory profile. The choice of product ingredients is crucial to ensure the optimal characteristics. The current study aims to provide a comprehensive framework for understanding the variability in the characteristics of a cleansing foam to achieve desired properties. The novelty of this study lies in the combination of ingredients for their potential synergistic and complementary effects in cleansing dry skin, as well as the application of Quality by Design (QbD) elements to develop and optimize the formulation of cleansing foam. The effects of varying the concentration of mild surfactants, polyols, and gel-forming agents on the properties of the gels and of the generated foams were studied. Significant influences of the formulation factors were observed: an increased ratio of xanthan gum positively impacted the texture properties of the gel, whereas higher concentrations of surfactants had a negative impact on these parameters. Additionally, increasing the polyols ratio was found to negatively influence the foaming property and stability of the foam. The study established an optimal formulation of a cleansing foam with a ratio of 0.45% xanthan gum, 26.19% surfactants and 2.16% polyols to be used for dry skin hygiene.

Neuroprotective efficiency of celecoxib vesicular bilosomes for the management of lipopolysaccharide-induced Alzheimer in mice employing 23 full factorial design

The aim of this study was to develop and evaluate bilosomes loaded with Celecoxib (CXB) for the efficient treatment of Alzheimer. The thin-film hydration approach was utilized in the formulation of CXB bilosomes (CXB-BLs). The study used a 23-factorial design to investigate the impact of several formulation variables. Three separate parameters were investigated: bile salt type (X1), medication amount (X2), and lipid–bile salt ratio (X3). The dependent responses included entrapment efficiency (Y1: EE %), particle size (Y2: PS), and zeta potential (Y3: ZP). The formulation factors were statistically optimized using the Design-Expert® program. The vesicles demonstrated remarkable CXB encapsulation efficiency, ranging from 94.16 ± 1.91 to 98.38 ± 0.85%. The vesicle sizes ranged from 241.8 ± 6.74 to 352 ± 2.34 nm. The produced formulations have high negative zeta potential values, indicating strong stability. Transmission electron microscopy (TEM) revealed that the optimized vesicles had a spherical form. CXB release from BLs was biphasic, with the release pattern following Higuchi's model. In vivo studies confirmed the efficiency of CXB-BLs in management of lipopolysaccharide-induced Alzheimer as CXB-BLs ameliorated cognitive dysfunction, decreased acetylcholinesterase (AChE), and inhibited neuro-inflammation and neuro-degeneration through reducing Toll-like receptor (TLR4), and Interleukin-1β (IL-1β) levels. The findings suggested that the created CXB-BLs could be a potential drug delivery strategy for Alzheimer's treatment.

Advancing Virtual Bioequivalence for Orally Administered Drug Products: Methodology, Real-World Applications and Future Outlook.

Bioequivalence studies are pivotal in generic drug development wherein therapeutic equivalence is provided with an innovator product. However, bioequivalence studies represent significant complexities due to the interplay of multiple factors related to drug, formulation, physiology, and pharmacokinetics. Approaches such as physiologically based biopharmaceutics modeling (PBBM) can enable virtual bioequivalence (VBE) assessment through appropriately developed and validated models. Such models are now being extensively used for bioequivalence risk assessment, internal decision-making, and the evaluation of drug and formulation factors related to bioequivalence. Depiction of the above-mentioned factors through the incorporation of variability and development of a virtual population for bioequivalence assessment is of paramount importance in utilizing such models. In this manuscript, we have portrayed our current understanding of VBE. A detailed explanation was provided with respect to study designs, in vivo variability, and the impact of physiological, drug, and formulation factors on the development of the population for VBE. Furthermore, strategies are suggested to incorporate variability in GastroPlus with an emphasis on intra-subject and inter-occasion variability. Two industrial case studies pertaining to immediate and modified release formulation were portrayed wherein VBE was utilized for decision-making and regulatory justification. Finally, regulatory understanding in the area of VBE, along with future perspectives, was detailed.

The silicone depletion in combination products induced by biologics

Silicone oil (SO) migration into the drug product of combination products for biopharmaceuticals during storage is a common challenge. As the inner barrel surface is depleted of SO the extrusion forces can increase compromising the container functionality. In this context we investigated the impact of different formulations on the increase in gliding forces in a spray-on siliconized pre-filled syringe upon storage at 2–8 °C, 25 °C and 40 °C for up to 6 months. We tested the formulation factors such as surfactant type, pH, and ionic strength in the presence of one monoclonal antibody (mAb) as well as compared three mAbs in one formulation. After 1 month at 40 °C, the extrusion forces were significantly increased due to SO detachment dependent on the fill medium. The storage at 40 °C enhanced the SO migration process but it could also be observed at lower storage temperatures. Regarding the formulation factors the tendency for SO migration was predominantly dependent on the presence and type of surfactant. Interestingly, when varying the mAb molecules, one of the proteins showed a rather stabilizing effect on the SO layer resulting into higher container stability. In contrast to the formulation factors, those different stability outcomes could not be explained by interfacial tension (IFT) measurements at the SO interface. Further characterization of the mAb molecules regarding interfacial rheology and conformational stability were not adequately able to explain the observed difference. Solely a hydrophobicity ranking of the molecules correlated to the stability outcome. Further investigations are needed to clarify the role of the protein in the SO detachment process and to understand the cause for the stabilization. However, the study clearly demonstrated that the protein itself plays a critical role in the SO detachment process and underlined the importance to include verum for container stability.

Study of the Effect of Preparation and Formulation Factors on the Stability of Vitamin C Microencapsulated by Solvent-Evaporation Method

This research studied the effect of formulation and processing variables on the stability of vitamin C or Ascorbic Acid (AA) encapsulated in Eudragit RS100 microparticles prepared using a solvent evaporation technique. Microparticles ranged in size from 60 to 102 μm and encapsulation efficiencies between 25% and 44% were obtained. Microencapsulation significantly enhanced the stability of AA compared to the free AA in solution. AA shelf life was extended up to 23 days. Increasing AA concentration and using sucrose or Tween 80 in the outer phase further enhanced AA stability. The results suggest that microencapsulation method under the investigated conditions is a promising approach for protecting AA from degradation in aqueous solutions.

Economic and Political Factors in Defense Strategy Formulation: a BRICS Country Perspective

This narrative provides a comprehensive analysis of the economic, political, and diplomatic factors influencing defense strategy formulation within the BRICS (Brazil, Russia, India, China, South Africa) context. Drawing on a wide range of sources, the narrative explores the historical evolution and recent shifts in BRICS defense strategies, highlighting the diverse approaches of member nations. The research adopts a qualitative descriptive approach, systematically gathering secondary data from academic journals, governmental reports, and reputable websites. The analysis focuses on the interplay between economic conditions, political dynamics, and defense strategy formulation in BRICS nations, providing nuanced insights into how these factors shape defense policies. It examines the influence of economic dependency on defense policies, emphasizing the role of economic stability in sustaining robust defense capabilities. Additionally, the narrative delves into the impact of political systems and leadership dynamics on defense strategy formulation, as well as the significance of diplomatic relations and security considerations. The findings underscore the complex interplay between economic, political, and defense factors within the BRICS framework, with implications for regional stability and resilience. The study finds that economic dependency is a pivotal factor in shaping BRICS defense strategies, with economic stability underpinning the capacity for robust defense capabilities. Political systems and leadership dynamics also play a crucial role, with centralized systems facilitating assertiveness and democratic frameworks emphasizing consensus-building. Diplomatic relations and security cooperation are integral to these strategies, highlighting the importance of strategic collaboration in addressing shared security challenges. The expansion of BRICS introduces new dynamics, particularly in energy investment and trade, requiring adaptive strategies to maintain stability and resilience. Finally, the narrative suggests future research directions to further explore these dynamics and enrich our understanding of BRICS defense strategies in the evolving global security landscape.

Formulation of Saxagliptin Oral Films: Optimization, Physicochemical Characterization, In-Vivo Assessment, and In-Vitro Real-Time Release Monitoring via a Novel Polyaniline Nanoparticles-Based Solid-Contact Screen Printed Ion-Selective Electrode

Oral dispersible films have received broad interest due to fast drug absorption and no first-path metabolism, leading to high bioavailability and better patient compliance. Saxagliptin (SXG) is an antidiabetic drug that undergoes first-path metabolism, resulting in a less active metabolite, so the development of SXG oral dispersible films (SXG-ODFs) improves SXG bioavailability. The formula optimisation included a response surface experimental design and the impact of three formulation factors, the type and concentration of polymer and plasticiser concentration on in-vitro disintegration time and folding endurance. Two optimised SXG-ODFs prepared using either polyvinyl alcohol (PVA) or hydroxypropyl methylcellulose were investigated. SXG-ODFs prepared with PVA demonstrated a superior rapid disintegration time, ranging from 17 to 890 s, with the fastest disintegration time recorded at 17 s. These short durations can be attributed to the hydrophilic nature of PVA, facilitating rapid hydration and disintegration upon contact with saliva. Additionally, PVA-based films displayed remarkable folding endurance, surpassing 200 folds without rupture, indicating flexibility and stability. The high tensile strength of PVA-based films further underscores their robust mechanical properties, with tensile strength values reaching up to 4.53 MPa. SXG exhibits a UV absorption wavelength of around 212 nm, posing challenges for traditional quantitative spectrophotometric analysis, so a polyaniline nanoparticles-based solid-contact screen-printed ion-selective electrode (SP-ISE) was employed for the determination of SXG release profile effectively in comparison to HPLC. SP-ISE showed a better real-time release profile of SXG-ODFs, and the optimised formula showed lower blood glucose levels than commercial tablets.Graphical

RESEARCH ON THE FORMULATION OF NANOPARTICLES CONTAINING MANGIFERIN USING SELF-ASSEMBLY METHOD

Background: The use of natural-origin active compounds in disease treatment is currently a prevailing trend. Mangiferin, a major component found in mangoes, is present in relatively high proportions. However, mangiferin's disadvantages include low solubility and poor permeability. There are numerous methods available to improve solubility and permeability, among which selfassembly is noteworthy. Self-assembly involves the combination of certain molecules or macromolecules to form three-dimensional networks or other structures with new characteristics, phospholipids and chitosan are often used as raw materials for the self-assembly process to create nanoparticles. This method offers advantages such as high efficiency, simple implementation, short execution time, high retention efficiency, and increased permeability through biological membranes. Objectives: To develop a formulation and process for producing nano mangiferin using the selfassembly method with phosphatidylcholine and chitosan. Materials and methods: The solubility of mangiferin in high-proof ethanol was investigated, followed by an assessment of the influence of formulation factors and processes on the characteristics of nano-sized mangiferin particles. Results: The average solubility of mangiferin in 96% ethanol was approximately 0.5529±0.0003 mg/mL. The mole ratio of mangiferin to Lipoid S100 was 1:1, and the mass ratio of Lipoid S100 to chitosan was 20:1. A stirring speed of 1.000 revolutions per minute, reflux temperature of 70°C, reflux time of 2 hours. homogenization speed of 1,000 revolutions per minute, and homogenization time of 15 minutes produced the smallest nanoparticles (103.44±0.46 nm), with a low polydispersity index (0.281±0.009≤ 0.3) and zeta potential (31.95±0.08 mV ≥ +30 mV), encapsulation efficiency of 82.42±0.53%; loading capacity of 32.97±0.95%. Conclusions: A successful formulation of nanosized mangiferin particles was achieved using the self-assembly method, resulting in particles that meet the criteria of small size, uniformity, and durability. Moreover, nearly 100% mangiferin release was achieved after 60 minutes, indicating the promising potential for developing highly bioavailable oral formulations.

Reactive Traffic Congestion Control by Using a Hierarchical Graph

Traffic management is one of the major factors in growth strategy formulation in urban centers across the globe. The increasing population and, therefore, the increase in the number of vehicles on roads in urban centers cause congested traffic patterns. These patterns typically emerge on intersections in busy city roads at various times during the day, especially during peak hours. A direct consequence of congestion is the increase in commute time and pollution. This paper presents a hierarchical graph-based congestion control (HGCC) method. Congestion values are set and evaluated as a two-level hierarchical graph. The least congestion path algorithm (LCP)is integrated with the HGCC to compute the optimal route between source and destination. The experimental results for a Manhattan-like grid network, together with the paired-sample t-test, show that the proposed method is efficient in achieving good congestion-avoiding routes.