Quality By Design Research Articles

Development of intestinal colonic drug delivery systems for diverticular disease: A QbD approach

This study aimed to advance the development of intestinal colon-coated sustained-release matrix tablets of metronidazole for diverticulitis treatment, employing the Quality by Design (QbD) methodology. Comprehensive Risk analysis and Risk evaluation were conducted to assess the potential risks associated with Critical Material Attributes (CMA) and Critical Process Parameters (CPP). Ishikawa diagram, color-coded risk classification and the Risk Priority Number (RPN) were used as tools for risk evaluation. A Design of Experiments (DoE) was executed using a fractional factorial design, incorporating five key factors derived from the Risk analysis and Risk evaluation. Two levels and a central point were established for each factor, resulting in 28 batches of coated tablets. The manufacturing process involved direct compression, followed by a coating process using pH-dependent or time-dependent polymers. Characterization and dissolution studies were conducted on all batches, and the obtained results underwent analysis of variance (ANOVA).The findings demonstrated the robustness and reproducibility of both the direct compression and coating processes. Statistical analysis identified HPMC/chitosan ratio, blending time, coating polymer, and coating weight gain as factors significantly impacting drug release. A Design Space was established to delineate the interplay of these factors, offering insights into various combinations influencing drug release behavior. Thus, the design space for 10 % weight gain formulations includes a range of HPMC/CH ratios between 2.7–3 and mixing times between 10 and 12 min; for 20 % weight gain formulations it includes a range of HPMC/CH ratios up to 2 and mixing times between 10 and 16 min. Multiple Linear Regression between technological and biopharmaceutical variables were optimized facilitating scale-up operations. Batches with a 10 % weight increase and varied HPMC viscosity grades and coating polymers achieve ∼50 % drug release at 24 h; however, batches with a 20 % weight increase along, with either high proportions of HPMC and short blending times or low proportions of HPMC and longer blending times, achieve slow release of metronidazole. This study contributes to optimizing metronidazole colonic delivery systems, enhancing their potential efficacy in diverticulitis treatment.

Bridging the Gap: Quality by Design as a Catalyst for Enhanced Quality Management Systems in Biopharmaceutical Manufacturing.

The document emphasizes the importance of addressing key issues in Quality Management Systems (QMS) to stay competitive and provide high-quality goods and services in a dynamic market. It highlights the need to adopt novel quality management techniques for long-term success. The fundamentals of Quality by Design (QbD) are discussed, tracing back to pioneers like Joseph M. Juran and the Six Sigma concept for effective implementation. QbD is described as a systematic approach focusing on risk management, Quality Target Product Profile (QTPP), and Critical Quality Attributes (CQAs) to create products meeting predetermined quality standards. QbD incorporates quality concepts into the development and production processes. Its goal is to guarantee the quality of the product by determining and managing important factors. Manufacturers can be flexible with it while still adhering to strict quality standards. It signifies a change in the industry's paradigm.

Quality by Design (QbD) Approach to Develop Colon-Specific Ketoprofen Hot-Melt Extruded Pellets: Impact of Eudragit® S 100 Coating on the In Vitro Drug Release.

A pelletizer paired with hot-melt extrusion technology (HME) was used to develop colon-targeted pellets for ketoprofen (KTP). Thermal stability and side effects in the upper gastrointestinal tract made ketoprofen more suitable for this work. The pellets were prepared using the enzyme-triggered polymer Pectin LM in the presence of HPMC HME 4M, followed by pH-dependent Eudragit® S 100 coating to accommodate the maximum drug release in the colon by minimizing drug release in the upper gastrointestinal tract (GIT). Box-Behnken Design (BBD) was used for response surface optimization of the proportion of different independent variables like Pectin LM (A), HPMC HME 4M (B), and Eudragit® S 100 (C) required to lower the early drug release in upper GIT and to extend the drug release in the colon. Solid-state characterization studies revealed that ketoprofen was present in a solid solution state in the hot-melt extruded polymer matrix. The desired responses of the prepared optimized KTP pellets obtained by considering the designed space showed 1.20% drug release in 2 h, 3.73% in the first 5 h of the lag period with the help of Eudragit® S 100 coating, and 93.96% in extended release up to 24 h in the colonic region. Hence, developing Eudragit-coated hot-melt extruded pellets could be a significant method for achieving the colon-specific release of ketoprofen.

Quality by Design (QbD) Enabled and Central-Composite Design Assisted Approach for Formulation of Oral Herbal Gastro-retentive In-situ Gel

Quality by Design (QbD) Enabled and Central-Composite Design Assisted Approach for Formulation of Oral Herbal Gastro-retentive In-situ Gel

A Review on QbD Approach in Analytical Method Development and Validation .

Quality by Design (QbD) is a cutting-edge pharmaceutical development that enhances analytical method robustness by emphasizing a thorough understanding of processes, risk management, and continuous improvement. Unlike traditional methods that often focus on end-product testing, QbD integrates quality into the development stages through a structured process. This involves defining the analytical target profile, identifying critical quality attributes, and employing the design of experiments to optimize method parameters. The implementation of QbD begins with a comprehensive understanding of the analytical objectives, leading to the identification of method variables that impact quality. Using risk assessment tools such as failure mode and effects analysis, developers can pinpoint potential risks and focus on areas of highest concern. Design of Experiments (DoE) plays a crucial role in this approach by exploring the interaction between variables and establishing a robust design space. Organizations can decrease variability, comply with regulations, and perform better methods when they adopt QbD concepts. This systematic approach not only minimizes the risk of method failures but also ensures consistent product quality, leading to increased patient safety and satisfaction. Furthermore, QbD facilitates faster development cycles and cost efficiencies by reducing the need for post-launch troubleshooting and modifications. This abstract provides a comprehensive overview of the role and significance of QbD in analytical method development, highlighting its components, benefits, and impact on the pharmaceutical industry.

Design and Optimization of Ibuprofen and Ranitidine Hydrochloride TriLayer Tablets in Immediate Release Formulation by Quality by Design.

The current trend in pharmaceutical process development and optimization is known as quality by design (QbD). This methodical approach is founded on the concept that quality should be integrated into the product from the start, rather than assessed after manufacture. In this study, we demonstrate methods to improve the process parameters for making tri-layer tablets by applying QbD principles in a methodical way. Dependent elements with high to medium impact on the process. According to the study’s results, all systems showed signs of instant release. It appears that the structure of each formulation and the properties of the polymer utilized have a significant impact on the rate and mechanism of drug release. Substantial medication release is observed in the three-layer formulations. Both the pace and mechanism of drug release are significantly affected by the tablet’s geometrical features and structure, as well as the weight and thickness of the barrier layers. While data suggested that Fickian diffusion was primarily responsible for drug release in two-layer tablets, three-layer tablets showed signs of either anomalous diffusion or erosion/relaxation. Therefore, the drug was stabilized as immediate-release directly compressible triple layered Average core weight of tri-layered tablets (mg) was 1000 for ibuprofen, 100 for placebo and 200 for ranitidine, thickness (mm) was 9.00 ± 0.3, hardness (N) was 110 ± 25, core tablet weight was 1300.000 ± 2% mg and coated tablet weight was 1325 mg. Using other moisture-sensitive medications. This study provides the foundation for future research into optimizing the properties of tablets made by direct compression.

Quality by Design for Preclinical In Vitro Assay Development.

Quality by Design (QbD) is an approach to assay development to determine the design space, which is the range of assay variable settings that should result in satisfactory assay quality. Typically, QbD is applied in manufacturing, but it works just as well in the preclinical space. Through three examples, we illustrate the QbD approach with experimental design and associated data analysis to determine the design space for preclinical assays.

Multivariate approaches for assessing dissolution behaviour of spironolactone. Dissolution-driven determination of polymorphic purity limits

Spironolactone (SPN) is an aldosterone antagonist effective for preventing and controlling cardiovascular diseases. Form I and Form II exhibit different behaviour in their dissolution properties, which can compromise the quality of the pharmaceutical formulation. Hence, in the present work, we propose the combination of two multivariate approaches to estimate the polymorphic purity of SPN in commercial tablets and predict the dissolution behaviour of these formulations considering their polymorphic composition. Multiple linear regression (MLR) approach was applied to model the dissolution behaviour of formulations depending on their polymorphic composition, showing excellent agreement among actual vs. predicted dissolution curves. This model was applied to establish a design space were the risks of dissolution failure due to the polymorphic purity was avoided. Next, to evaluate the purity of Form II of SPN in formulated products, two quantitative partial least squares (PLS) models were developed based on near (NIR) and mid (MIR) infrared spectroscopies. Training (n = 14) and validation (n = 8) sets were prepared by mixing both polymorphs and the excipient matrix to simulate commercial tablets. Methodologies showed recoveries non-statistical different from 100 %, but MIR-PLS model showed a higher dispersion (100.1 ± 1.82 % and 99.5 ± 6.94 % for NIR and MIR, respectively). Similar values of Form II content (1.02 ± 0.01 w/w with NIR and 1.03 ± 0.03 w/w with MIR) were obtained during the analysis of commercial and spiked SPN tablets. Finally, NIR-PLS was coupled to MLR model for the prediction of dissolution in entire tablets based on polymorphic composition to act as Quality by Design (QbD) tool. The full coincidence among actual and NIR-MLR predicted curves validated the final purpose of this approach.

A Review on the Progress of QbD Approach in Nanosystems Optimization: Current Updates and Strategic Applications

: Nanotechnology has made great strides in developing targeted drug delivery systems over the past few decades. These systems have garnered attention for their unique biological properties and ability to deliver drugs in a stable and sustainable manner. Despite these advances, there are still concerns about quality, efficacy, and safety. Many fabrication techniques still need to be refined to address the complex structures and non-standard manufacturing processes that can impact the quality of drug delivery systems. Recently, optimization techniques such as Quality by Design (QbD) have gained popularity in the pharmaceutical industry. QbD is a structured approach that addresses many technological and trait-related issues by providing a deep understanding of the product and its operations. This review examines the current state of QbD in the design of various nano-drug delivery systems, including lipid nanoparticles, lipid carriers, nano micelles, beaded drug delivery systems, nanospheres, cubosomes, and novel cosmeceuticals. Various mathematical models and statistical tests have been used to identify the parameters that influence the physical characteristics of these nanosystems. Critical process attributes such as particle size, yield, and drug entrapment have been studied to assess risk factors during development. However, critical process parameters are often identified through trial and error. This review highlights common material attributes and process parameters that affect the quality of nano-drug delivery systems. Hence, this survey has disclosed the various material attributes and process parameters, quality variables of different nano-drug systems. QbD designs such as Central drug composite, Design of experiment, D-optimal Design, Box-Benkhen Design, and Face center Design in optimizing the nanosystems have also been added. Conclusively, QbD optimization in nano drug delivery systems is expected to be a time-honored strategy in the forthcoming years.

Quality by design for mRNA platform purification based on continuous oligo-dT chromatography

Oligo-deoxythymidine (Oligo-dT) ligand-based affinity chromatography is a robust method for purifying mRNA drug substances within the manufacturing process of mRNA-based products, including vaccines and therapeutics. However, the conventional batch mode of operation for oligo-dT chromatography has certain drawbacks that reduce this process’s productivity. Here, we report a new continuous oligo-dT chromatography process for the purification of in vitro transcribed mRNA, which reduces losses, improves the efficiency of oligo-dT resin use, and intensifies the chromatography process. Furthermore, the quality by design (QbD) framework was used to establish a design space for the newly developed method. The optimisation of process parameters, including salt type, salt concentration, load flow rate and mRNA load concentration both in batch and the continuous mode, achieved >90% yield (mRNA recovery) along with >95% mRNA integrity and >99% purity. The productivity of continuous chromatography was estimated to be 5.75-fold higher, and the operating cost was estimated 15% lower, when compared to batch chromatography. Furthermore, the QbD framework was further used to map the relationship between critical quality attributes (CQAs) and key performance indicators (KPIs) as a function of critical process parameters (CPPs) and critical material attributes (CMAs).

Investigation of Chlorhexidine and Chitosan Gel-Based Coatings for the Prevention of Intravascular Catheter-Associated Infections Following Quality by Design Approach.

Intravascular catheter-associated infections pose a significant threat to the health of patients because of biofilm formation. Hence, it is imperative to exploit cost-effective approaches to improve patient compliance. With this aim, our present study reported the potential of an antimicrobial polymeric gel coating of chitosan (CS) and chlorhexidine (CHX) on the marketed urinary catheters to minimize the risk of biofilm formation. The study involved the implementation of the Quality by Design (QbD) approach by identifying the critical parameters that can affect the coating of the catheter's surface in any possible way. Later, design of experiments (DoE) analysis affirmed the lack of linearity in the model for the studied responses in a holistic manner. Moreover, in vitro studies were conducted for the evaluation of various parameters followed by the antibiofilm study. The coating exhibited promising release of CHX in the artificial urinary media together with retention of the coating on the catheter's surface. Therefore, this study aims to emphasize the importance of a systematic and quality-focused approach by contributing to the development of a safe, effective, and reliable catheter coating to enhance intravascular catheter safety.

Quality by design (QbD) based approach for development of itraconazole loaded transferosomes for skin cancer: In vitro, ex vivo and cell line studies

Objective Itraconazole (ITZ), a widely used systemic antifungal drug, has been ingeniously repurposed for its antitumor effects. In the present work, we have prepared and optimized the ITZ-loaded transferosomes by Quality by Design (QbD) approach and repurposed them for skin cancer. Methods The transferosomal formulation was optimized by employing a QbD approach with the design of experiment. A combination of screening and optimization design was used for formulation optimization. The optimized formulation was characterized by particle size, PDI, zeta potential, FTIR, XRD, and surface morphology using TEM. In vitro and ex vivo studies were performed using Franz diffusion cells. An in vitro cell line study was performed on the human melanoma A375 cell line. Results The optimized formulation has a particle size of 192.37 ± 13.19 nm, PDI of 0.41 ± 0.03, zeta potential -47.80 ± 3.66, and an entrapment efficiency of 64.11 ± 3.75%. In vitro release studies showed that ITZ encapsulated transferosomes offer higher and sustained release than pure drugs. Ex vivo drug penetration and retention studies show that the penetration and retention of transferosomes are more visible in the skin than in the drug. The cell viability study confirms that ITZ encapsulated transferosomes have almost 2-fold more potency against the A375 cell line than pure drug. Conclusion ITZ encapsulated transferosomes were successfully prepared and optimized using a combination of screening and optimization designs. Based on ex vivo and cell line studies, we conclude that ITZ-loaded transferosomes could aid melanoma management alongside standard therapies.

Development and validation of a method for the simultaneous estimation of terpinene-4-ol and 1,8-cineole in Melaleuca alternifolia (Maiden & Betche) Cheel and Rosmarinus officinalis L. oil using HPTLC coupled with a QbD approach

This paper comprehends a Quality by design (QbD) approach for development of a simple and precise HPTLC (High performance thin layer chromatography) method for simultaneous estimation of the phytoconstituents terpinen-4-ol and 1,8-cineole found in Melaleuca alternifolia (tea tree oil) and Rosmarinus officinalis (rosemary oil) respectively. The method was optimized by Design expert software using response surface methodology. The chromatographic condition optimized by using software was, mobile phase as hexane: ethyl acetate: glacial acetic acid in the ratio of 8.5:1.5:0.47 % v/v, stationary phase as TLC plates precoated with silica gel 60 F254 at ambient temperature conditions and saturation time 20 min at 366 nm. Optimized conditions were verified and validated as per ICH Q2 (R1) (International council for harmonization of technical requirements of pharmaceuticals for human use) guidelines. The method developed was validated for the parameters such as specificity, linearity, DL, QL, accuracy and precision. This method was then applied for simultaneous estimation of terpinen-4-ol and 1,8-cineole in Melaleuca alternifolia (tea Tree oil) and Rosmarinus officinalis (rosemary oil) respectively.

Hansen solubility parameters and quality-by-design oriented optimized cationic nanoemulsion for transdermal drug delivery of tolterodine tartrate

Tolterodine tartrate (TOT) is a selective anti-muscarinic drug to treat urinary urgency and overactive urinary bladder (OAB) occurring in children, renal disease and elderly patients. Oral delivery is associated with several adverse effects. We addressed HSPiP and QbD (quality by design)-oriented TOT loaded cationic nanoemulsions for transdermal delivery. Hansen solubility parameters (HSP) screened excipients based on theoretical solubility whereas, QbD optimized cationic nanoemulsions (CNE-TOT-6). Formulation characteristic parameters were desirable to execute targeted in vitro drug release and ex vivo permeation profiles. In vitro hemolysis was conducted at varied concentrations whereas, histopathological study supported the safety aspect of CNE-TOT6. A comparative bioavailability was carried out in a rat model. Capmul PG8 (CAP), tween 80, and PEG 400 (polyethylene glycol 400) were screened based on HSP and experimental solubility data. QbD suggested optimized content of CAP, tween 80, and PEG 400 to achieve the lowest value of size (184 nm), maximum % entrapment efficiency (87.2 %), high zeta potential (+32.6 mV), optimum viscosity (47.19 cP), and high extrudability (96 %) as compared to its gel. High gel consistency slowed down the drug release and permeation flux as compared to CNE-TOT6 suspension. Hemocompatible CNE-TOT6 increased pharmacokinetic parameters as compared to the control and gel without causing skin toxicity after application. Thus, HSPiP and QbD oriented cationic nanoemulsions are promising carriers to treat overactive urinary bladder.

A Quality by Design (QBD) Approach for the Development and Validation of RP-HPLC Method for the Quantification of Silymarin Tablet

This study emphasizes the crucial role of Quality by Design (QbD) in developing pharmaceutical procedures, particularly in risk assessment. It demonstrates how QbD principles were applied to create a precise and effective HPLC method for Silymarin Tablets, ensuring consistent quality within specified criteria. The optimized method, developed using a Design of Experiment approach, employs a C18 column (150 mm x 4.6 mm, 5μm) with isocratic elution using a 95:25 ratio of acetonitrile to orthophosphoric acid buffer (pH 3). Peaks were detected using a PDA detector calibrated at 287 nm, with a flow rate of 1.0 mL/min. The column oven temperature was maintained at 25°C, and a 10 μL injection volume was used. Thorough validation, adhering to USP <1225> and ICH Q2 (R1) standards, ensures the method's reliability. Key factors such as accuracy, precision, robustness, limit of detection (LOD), and limit of quantification (LOQ) were comprehensively assessed. The method exhibits exceptional sensitivity, selectivity, efficiency, precision, accuracy, and cost-effectiveness, making it ideal for pharmaceutical analysis of Silymarin tablets. It has been validated to effectively differentiate between marketed products, including those closely resembling the original. This method is intended for routine quality control analysis in the pharmaceutical industry, highlighting its suitability and reliability for ongoing use.

A novel QbD HPLC approach for the concurrent analysis of amoxicillin, amprolium, and ethopabate in food samples and dosage forms

A simple, rapid, and sensitive reversed-phase HPLC method coupled with photodiode array detection (PDA) was developed for the simultaneous estimation of three co-administered antibacterial drugs, amprolium, ethopabate, and amoxicillin for the first time. An analytical quality-by-design (QbD) approach was adopted to optimize the developed approach. A two-level full factorial design (25 FFD) was implemented to optimize how variable factors affected chromatographic responses. On a Hypersil BDS C18 column, the chromatographic separation was carried out using isocratic elution at 40.1 °C. The mobile phase consisted of methanol: potassium phosphate buffer containing 5.76 mM heptane sulphonate (9.05 mM; pH 3.32, 44.8:55.2 % v/v) pumped at a flow rate of 0.8 mL/min and an injection volume of 20.0 μL. In less than 7 min, the suggested method was able to separate the ternary mixture with a challenging ratio of 1: 15.6: 1 for amoxicillin, amprolium, and ethopabate, respectively. The calibration curves showed excellent linearity over the concentration ranges of 0.50–30.0, 0.30–30.0, and 0.05–20.0 μg/mL, respectively. Recovery percentages ranged from 90.30 % to 111.13 % with %RSD less than 2 % were obtained upon spiking to chicken tissues, liver, and egg samples, indicating the suitability of the proposed method for determining of the studied drugs in complicated food matrices. Furthermore, the proposed method was successfully applied to determine the studied drugs in their commercial formulations. Full validation was carried out according to ICHQ2 (R1) guidelines. Finally, the method's greenness and ecofriendliness were evaluated using various metrics tools, including the Green Analytical Procedure Index (GAPI) and Analytical GREEnness (AGREE).

HSPiP and QbD oriented optimized stearylamine-elastic liposomes for topical delivery of ketoconazole to treat deep seated fungal infections: In vitro and ex vivo evaluations

The study explored stearylamine containing cationic elastic liposomes to improve topical delivery and efficacy of ketoconazole (KETO) to treat deeply seated fungal infections. Stearylamine was used for dual functionalities (electrostatic interaction and flexibility in lipid bilayer). Hansen solubility program (HSPiP) estimated Hansen solubility parameters (HSP) based on the SMILE file and structural properties followed by experimental solubility study to validate the predicted values. Various formulations were developed by varying phosphatidylcholine and surfactants (tween 80 and span 80) concentration. To impart cationic properties, stearylamine (1.0 %) was added into the organic phase. Using quality by design (QbD) method, we optimized the formulations and evaluated for vesicle size, polydispersity index, zeta potential, morphology (scanning electron microscopy), in vitro drug release (%), and ex vivo permeation profiles. Result showed that there is a good correlation (0.65) between HSPiP predicted and actual experimental solubility of KETO in water, chloroform, S80, and tween 80. Spherical OKEL1 showed an established correlation between the predicted and the actual formulation parameters (size, zeta potential, and polydispersity index) (259 nm vs 270 nm, +2.4 vs 0.21 mV, and 0.24 vs 0.27). OKEL1 was associated with the highest value of %EE (83.1 %) as compared to liposomes. Finally, OKEL1 exhibited the highest % cumulative permeation (49.9 %) as compared to DS (13 %) and liposomes (25 %). Moreover, OKEL1 resulted in 4-fold increase in permeation flux as compared to DS which may be attributed to vesicular mediated improved permeation and gel based compensated trans epidermal water loss in the skin. The drug deposition elicited OKEL1 and OKEL1-gel as suitable carriers for maximum therapeutic benefit to treat deeply seated fungal infections.

Development of an Intranasal In Situ System for Ribavirin Delivery: In Vitro and In Vivo Evaluation.

Recently, ribavirin has demonstrated effectiveness in treating glioblastoma through intranasal administration utilizing the nose-to-brain delivery route. Enhancing ribavirin's bioavailability can be achieved by utilizing intranasal stimuli-responsive systems that create a gel on the nasal mucosa. The research examined thermosensitive, pH-sensitive, and ion-selective polymers in various combinations and concentrations, chosen in line with the current Quality by Design (QbD) approach in pharmaceutical development. Following a thorough assessment of key parameters, the optimal composition of gellan gum at 0.5%, Poloxamer 124 at 2%, and purified water with ribavirin concentration at 100 mg/mL was formulated and subjected to in vivo testing. Through experiments on male rats, the nose-to-brain penetration mechanism of the active pharmaceutical ingredient (API) was elucidated, showcasing drug accumulation in the olfactory bulbs and brain.

Quality by Design Approach for the Development and Validation of a Robust RP-HPLC Method for the Estimation of Aloe-Emodin

Introduction/Objective: The current study examines the methodical Quality by Design (QbD) that facilitated the creation of an easy-to-use, quick, affordable, and stability-indicating reversed- phase high-performance liquid chromatography (RP-HPLC) technique for the efficient analysis of aloe-emodin. Methods: The chromatographic conditions were optimized with the Design Expert software 11.0 version, i.e., flow rate, buffer concentration, and column temperature. Results: The results of the linearity graph show R2 = 0.9988. The LOQ was 0.07949 μg/mL and the LOD was 0.02623 μg/mL. According to ICH rules, the technique validation parameters were within the allowed range. Utilizing the Design Expert 11.0 version, the Box–Behnken design experimental design explains the relationships between flow rate, buffer concentration, and column temperature at three distinct levels. The responses were monitored: the retention time (Rt), tailing factor (Tf), and number of theoretical plates (NTPs). Conclusion: The suggested approach was appropriate for quantitative determination and may be used in clinical pharmacokinetic investigations, biopharmaceutics, accredited testing laboratories, and quality control departments in enterprises.

Quality by Design Optimization of Telmisartan-loaded Self-nanoemulsifying Drug Delivery Systems

Aim: This study aimed to develop a QbD-based SNEDDS for Telmisartan to enhance its biopharmaceutical performance. Background: Quality by Design (QbD) was incorporated by selecting the Critical Process Pa-rameters (CPPs) as influential variables upon the desired responses. Using Design of Experiments (DoE) software, oil, and S/CoS were tested for pre-isotropic compatibility and formulation im-provement. A heating-cooling cycle and phase separation were used to determine the formula-tions' dispersibility, self-emulsifying time, mean globule size, and stability. Objective: Using Design of Experiments (DoE) software, oil (Capmul MCM C-10) and surfactant (Labrasol)/co-surfactant (Tween-20, and PEG-600) (S/CoS) ratios were optimized for pre-isotropic compatibility and formulation improvement. Methods: Aerosil-200, Sylysia-350, 550, and 730 were used as porous carriers, and Neusilin US2 as an adsorbing agent resulted in free-flowing granules of self-nano emulsifying drug delivery systems. The SNEDDS was further formulated into tablets using a direct compression technique with enhanced disintegration properties. Results: The prepared SNEDDS tablets exhibited a 71% increase in drug dissolution as compared to the pure drug and marketed formulation after the in vitro dissolution studies. Conclusion: This QbD approach offers a promising strategy for developing SNEDDS formula-tions for poorly soluble drugs like Telmisartan.