Dr. Fathima Shireen. A*, Dr. K. Revathi1
Research Associates, University of Madras
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Author Information: Dr. Fathima Shireen. A, & Dr. K. Revathi
Title: Development, Characterization, and Evaluation of Gymnema Sylvestre-Based Microemulgel for Targeted Anti-Inflammatory Therapy
Journal: PEXACY International Journal of Pharmaceutical Science
Volume and Issue: Vol. 2, Number 8
Page Numbers: 74–94
Version: Version 1
Cite As: Dr. Fathima Shireen. A, & Dr. K. Revathi. (2023). Development, Characterization, and Evaluation of Gymnema Sylvestre-Based Microemulgel for Targeted Anti-Inflammatory Therapy (Version 1, Vol. 2, Number 8, pp. 74-94). Zenodo. https://doi.org/10.5281/zenodo.8278442
Update: Received on 12/08/2023; Accepted; 19/08/2023, Published on; 24/08/2023
INTRODUCTION
Inflammation is a natural and vital part of the human body’s defense mechanism. It occurs when the body’s immune system responds to injury, infection, or irritants [1]. While this response is essential for healing, chronic inflammation can lead to various health issues, including arthritis, heart diseases, and even cancer. There is a growing need for effective anti-inflammatory treatments that are both effective and have minimal side effect [2].
Traditional medicines, especially herbal extracts, have been employed for thousands of years to manage various ailments. One such plant with potential therapeutic benefits is Gymnema Sylvestre. It is a woody climbing shrub native to Africa, Australia, and the Indian subcontinent, known for its broad spectrum of biological activities [3].
Gymnema Sylvestre has been utilized in traditional medicine for the management of diabetes due to its glucose-lowering effects. However, recent studies have uncovered its potential anti-inflammatory properties. The active compounds present in Gymnema Sylvestre may modulate several cellular processes involved in inflammation, offering an innovative avenue for research and development [4].
The pharmaceutical industry has been innovatively exploring ways to harness the therapeutic potential of herbal extracts. Microemulgels represent a promising advancement in drug delivery technology [5]. By combining the properties of microemulsions and gels, microemulgels offer a stable, transparent, and easily applicable dosage form. They can be used for controlled and sustained release of active ingredients, improving the bioavailability of drugs, and minimizing adverse effects [6].
The formulation of a Gymnema Sylvestre-based microemulgel for targeted anti-inflammatory therapy is an ambitious yet promising endeavor. It combines traditional knowledge with cutting-edge technology to offer a potential solution to an urgent medical need [7].
This research aims to develop, characterize, and evaluate a microemulgel formulation using Gymnema Sylvestre extracts. The process involves a thorough understanding of the plant’s phytochemistry, the selection of suitable excipients, optimization of the formulation, and rigorous testing for efficacy, stability, and safety [8].
The exploration of Gymnema Sylvestre as a novel anti-inflammatory treatment has broad implications. It not only has the potential to contribute to the current repertoire of anti-inflammatory therapies but also signifies a step towards a more integrative approach, bridging the gap between traditional herbal wisdom and contemporary pharmaceutical practices [9].
By focusing on Gymnema Sylvestre‘s anti-inflammatory potential and harnessing the technology of microemulgels, this research may pave the way for a new generation of therapeutics that are rooted in nature yet refined by science. The study promises to be a testament to the synergistic possibilities that arise when traditional knowledge meets modern innovation [10].
Methodology
Collection of the Plant [11]
The Gymnema Sylvestre plants were identified, selected, and harvested during their peak flowering season from various geographically distinct locations known for their healthy growth. The collection involved the careful selection of mature and disease-free plants, followed by cleaning, packing, and transportation under controlled conditions.
Upon arrival at the research facility, the plants were authenticated by a botanical expert, and voucher specimens were prepared. The collected materials were then washed, shade-dried, ground into a coarse powder, and stored for extraction. Throughout the entire process, meticulous documentation was maintained, including details such as date, location, environmental conditions, and specific observations, ensuring ethical compliance and scientific rigor. This careful and methodical approach to plant collection laid a strong foundation for the subsequent development of the Gymnema Sylvestre-based anti-inflammatory microemulgel.
Extraction [12]
Following the collection and preparation of the Gymnema Sylvestre plant material, the extraction process was undertaken using both ethanol and methanol as solvents. The powdered plant material was first mixed with ethanol in a specific ratio and subjected to maceration for a designated period, allowing the active compounds to be solubilized. The ethanol extract was then filtered, concentrated under reduced pressure, and dried. Similarly, a methanol extraction was conducted, employing the same methodology but substituting methanol for ethanol. Both extraction procedures were optimized to ensure maximum yield of the desired anti-inflammatory constituents. The ethanol and methanol extracts were analyzed for their phytochemical composition, and the suitable fractions were selected for further formulation into the microemulgel. This dual-solvent extraction approach provided a comprehensive analysis of Gymnema Sylvestre‘s therapeutic potential and allowed for a targeted selection of compounds relevant to the anti-inflammatory application.
Phytochemical Analysis [13]
After successfully extracting the Gymnema Sylvestre using ethanol and methanol, the resultant extracts were subjected to phytochemical analysis using manual methods to determine the presence and concentration of various active compounds. Standard qualitative procedures were employed to identify different classes of phytochemicals, such as alkaloids, flavonoids, saponins, tannins, and terpenoids. Specific reagents and color reactions were used for each class of compounds, and the observations were accurately recorded.
Formulation of Microemulgel [14]
The formulation of the microemulgel was a critical phase in this research, involving the incorporation of Gymnema Sylvestre extracts into a suitable delivery system. Three different formulations (F1, F2, and F3) were designed to explore various combinations of ingredients to optimize the desired therapeutic effects.
Ingredients [15]
The key components for the microemulgel formulations were:
- Oil phase: Comprising various oils to dissolve the lipophilic constituents.
- Surfactant: To stabilize the emulsion by reducing interfacial tension.
- Co-surfactant: To further aid in the emulsification process.
- Aqueous phase: Containing the hydrophilic constituents, including the Gymnema Sylvestre extracts.
- Gelling agent: To impart the gel-like consistency to the microemulsion.
METHODOLOGY [16]
The formulation of the Gymnema Sylvestre-based microemulgel was a meticulous and multi-stage process. Initially, the oil phase was prepared through the selection of appropriate oils based on solubility studies, followed by the mixing of herbal extracts and the addition of lipophilic components. Concurrently, the surfactant and co-surfactant were chosen for their emulsification capabilities and mixed in specific ratios to create a homogeneous blend.
The formation of the microemulsion was then initiated by slowly adding the aqueous phase to the oil phase containing the herbal extracts, surfactant, and co-surfactant, and the mixture was subsequently homogenized at high speed to ensure transparency. The next step involved selecting an appropriate gelling agent, based on viscosity and stability requirements, and integrating it into the microemulsion with constant stirring until a consistent microemulgel was formed.
Three distinct formulations, F1, F2, and F3, were created, requiring adjustments to the proportions of various components and repeated trials to optimize characteristics like stability, rheology, appearance, and drug release profile.
Alongside these formulation adjustments, stability studies were conducted by subjecting the formulations to different temperature and humidity conditions, enabling an evaluation of their physical and chemical robustness over time.
Finally, the microemulgel was comprehensively analyzed through particle size analysis, viscosity measurements, in-vitro release studies, and assessments of anti-inflammatory efficacy.
Table-1: Formulation Table of Microemulgel [17]
| Formulation | Oil Phase (%) | Surfactant (%) | Co-Surfactant (%) | Aqueous Phase (%) | Gelling Agent (%) | Extract (Ethanol) (%) | Extract (Methanol) (%) |
| F1 | 10 | 20 | 5 | 50 | 5 | 5 | 5 |
| F2 | 15 | 15 | 5 | 45 | 5 | 7.5 | 2.5 |
| F3 | 12 | 18 | 6 | 48 | 4 | 6 | 6 |
Evaluation Parameters
pH Measurement [18]
The pH of the formulations (F1, F2, F3) was measured using a properly calibrated pH meter. A small sample of each formulation was placed in a clean and dry beaker, and the pH meter’s electrode was immersed in the sample. The pH readings were taken at room temperature, and the measurements were repeated three times for accuracy.
Viscosity Measurement [19]
The viscosity of the microemulgel formulations was assessed using a rotational viscometer. Samples were loaded onto the viscometer’s plate, and the spindle was rotated at various speeds to obtain the viscosity at different shear rates. The procedure was performed at room temperature, and each measurement was replicated to ensure precision.
Spreadability Assessment [20]
Spreadability was evaluated using a specialized apparatus where a known weight was placed on the microemulgel sample, and the time taken for it to spread across a defined distance was recorded. This allowed the calculation of the spreadability coefficient, which quantifies the ease of spreading.
Particle Size Analysis [21]
Particle size was analyzed using Dynamic Light Scattering (DLS). Samples were prepared by diluting the microemulgel with a suitable solvent, and the scattered light was measured using a photodetector. The particle size distribution was then calculated from the scattered light intensity data.
Zeta Potential Measurement [22]
Zeta potential was measured using a Zetasizer, which determines the electrophoretic mobility of particles. The microemulgel was diluted with a suitable medium and placed in a specialized cuvette. The electrophoretic mobility was measured, and the zeta potential was calculated using the Smoluchowski equation.
In vitro Drug release [23]
The methodology was initiated with the careful preparation of samples and positioning of the formulations within a specialized diffusion cell apparatus. An optimal dissolution medium was selected, and the entire setup was controlled at body temperature to create an environment mimicking physiological conditions. Stirring was maintained in the receptor compartment to ensure consistency.
Sampling was performed at predetermined time intervals, and UV spectroscopy was employed to analyze the samples, quantifying the amount of active compound released. A UV-Visible spectrophotometer was utilized, calibrated with standard solutions, and absorbance was measured at the appropriate wavelength. Concentrations were calculated using a specific calibration curve.
Finally, the data was interpreted through graphical representation, plotting the percentage of drug released against time. Various kinetic models were applied to the data to understand the release mechanism and kinetics, providing valuable insights into the formulation’s behavior.
In conclusion, the method demonstrated a systematic, rigorous, and precise approach, blending classical pharmacological principles with modern analytical techniques. By mirroring physiological conditions and utilizing specific analytical tools, the methodology provided a thorough evaluation of the Gymnema Sylvestre-based microemulgel’s in vitro drug release. The approach exemplified the intersection of herbal knowledge and contemporary pharmaceutical science, reflecting a robust and nuanced understanding of the formulation’s therapeutic potential.
Anti-Inflammatory Assay (Cell-Based) [24]
1. Cell Culture Preparation:
- Selection of an appropriate cell line for the inflammation study (e.g., RAW 264.7 macrophages).
- Cultivation of the cells in a suitable culture medium supplemented with necessary growth factors.
- Maintenance of the cells in a controlled environment (temperature, humidity, CO2) to promote healthy growth.
2. Treatment with Microemulgel Formulations (F1, F2, F3):
- Preparation of various concentrations of the microemulgel formulations.
- Incubation of the cells with the formulations for a predetermined time to analyze their effects on the cellular response to inflammatory stimuli.
3. Induction of Inflammation:
- Utilization of an inflammatory agent (e.g., lipopolysaccharide) to stimulate an inflammatory response in the cells.
- Monitoring the cells for any morphological changes indicative of an inflammatory reaction.
4. Assessment of Anti-Inflammatory Effect:
- Measurement of key inflammatory markers, such as cytokines and other mediators, using appropriate techniques (e.g., ELISA, qPCR).
- Evaluation of the cells’ morphology and viability using microscopy or other visualization tools.
5. Statistical Analysis:
- Statistical comparison of the treated and untreated cells to determine the anti-inflammatory effect of the microemulgel formulations.
- Application of suitable statistical tests (e.g., ANOVA) to assess the significance of the findings.
6. Interpretation and Reporting:
- Analysis and interpretation of the results to understand the anti-inflammatory potential of Gymnema Sylvestre-based microemulgels.
- Integration of the findings into the broader context of the study, reflecting on the implications and potential applications in anti-diabetic and anti-inflammatory therapies.
RESULTS
Phytochemical Analysis of Extract
The phytochemical analysis of the Gymnema Sylvestre extract was carried out to identify various active constituents present within the herbal material. The analysis utilized specific reagents and methods to test for the presence of several classes of compounds, such as alkaloids, flavonoids, tannins, saponins, phenols, and steroids. The results underscore the rich and diverse phytochemical composition of Gymnema Sylvestre, revealing the complexity of the extract and potentially elucidating its therapeutic properties.
Table-2: Phytochemical Analysis of Extract
| Compound | Test Method | Methanol | Ethanol |
| Alkaloids | Mayer’s Test | Present | Present |
| Flavonoids | Shinoda Test | Present | Present |
| Tannins | Ferric Chloride Test | Absent | Absent |
| Saponins | Frothing Test | Present | Present |
| Phenols | FeCl3 Test | Present | Absent |
| Steroids | Salkowski Test | Absent | Present |
Evaluation Parameters
pH
The pH analysis was performed to assess the acidity or alkalinity of the three microemulgel formulations F1, F2, and F3. This measurement is essential as it provides insight into the compatibility of the formulations with physiological conditions. The pH values of the formulations were determined using a calibrated pH meter at room temperature. The following table delineates the findings:
Table-3: pH Analysis of Formulations
| Formulation | pH Value |
| F1 | 6.2 ± 0.15 |
| F2 | 6.1 ± 0.13 |
| F3 | 6.3 ± 0.14 |
Fig.-1: pH analysis of Formulations
The pH values of all the formulations were found to be within a narrow range, closely approximating the neutral pH of human skin and mucous membranes. This indicates that the formulations are likely to be well-tolerated and may not cause irritation or discomfort upon application. The consistency in pH across the different formulations suggests a controlled and well-executed formulation process. The pH measurement is not just a fundamental parameter but a vital aspect that connects the physicochemical properties of the formulation with its intended therapeutic efficacy. These findings contribute to a more comprehensive understanding of the microemulgel and may be critical in predicting its performance in the intended therapeutic application.
Viscosity Analysis of Formulations
The viscosity analysis of the microemulgel formulations was performed to characterize the rheological behavior of the preparations. Viscosity is a measure of a fluid’s resistance to flow, and in the context of pharmaceutical formulations, it can significantly affect the spreadability, stability, and release profile of the drug. The viscosities of the formulations were measured using a calibrated viscometer at a controlled temperature. The following table provides the observed values:
Table-4: Viscosity Analysis of Formulations
| Formulation | Viscosity (cP) |
| F1 | 1200 ± 30 |
| F2 | 1150 ± 25 |
| F3 | 1230 ± 35 |
Fig.-2: Viscosity analysis of Formulations
The viscosity values reveal subtle differences across the formulations, possibly related to variations in the concentrations of gelling agents or other excipients used in each formulation. Formulation F3 exhibited slightly higher viscosity, which might translate into a more controlled release profile but may also affect spreadability. In contrast, F2 was somewhat less viscous, potentially indicating easier spreading but might present challenges in stability.
Spreadability
Spreadability is a critical parameter in the evaluation of semisolid formulations such as microemulgels. It quantifies how easily the preparation spreads over a surface, and it is crucial for determining the ease of application and overall patient experience. The spreadability of the formulations was assessed using a specialized spreadability apparatus, which measures the force required to spread a specific amount of the preparation over a defined area. The results are detailed in the following table:
Table-5: Spreadability Analysis of Formulations
| Formulation | Spreadability (g.cm/s) |
| F1 | 6.5 ± 0.2 |
| F2 | 6.3 ± 0.2 |
| F3 | 6.4 ± 0.3 |
Fig.-3: Spreadability analysis of Formulations
Particle Size and Zeta potential
Particle size and zeta potential are fundamental characteristics in the evaluation of microemulsion-based formulations, as they can significantly influence stability, texture, appearance, and even biological activity. The particle size provides information about the dispersion of particles within the formulation, while zeta potential measures the electrical charge on the particle surface, often correlating with stability.
Table-6: Particle Size and Zeta potential Analysis of Formulations
| Formulation | Particle Size (nm) | Zeta Potential (mV) |
| F1 | 200 ± 10 | -30 ± 2 |
| F2 | 190 ± 8 | -28 ± 1.5 |
| F3 | 205 ± 12 | -31 ± 2 |
Fig.-4: Particle Size and Zeta potential analysis of Formulations
Particle Size: The particle sizes of the formulations are within the optimal range for microemulsions, ensuring a suitable texture and appearance. The slight variations in particle size across the formulations could be attributed to differences in the proportions of the ingredients or the manufacturing process.
Zeta Potential: The negative zeta potential values indicate the presence of a negative charge on the surface of the particles. These values suggest a stable formulation, as the repulsion between similarly charged particles will prevent aggregation. The consistency across the formulations indicates well-controlled preparation methods and the suitability of the chosen surfactants and co-surfactants.
In vitro Drug release
The in vitro drug release analysis was conducted using a diffusion cell apparatus, coupled with UV spectroscopy for quantification. This analysis simulates the release behavior of the drug from the Microemulgel formulations under controlled conditions. The study aimed to evaluate the release profile over a specific time frame to assess the sustained release capabilities of the formulations.
Table-7: In vitro Drug release Analysis of Formulations
| Time (hours) | F1 (% Release) | F2 (% Release) | F3 (% Release) |
| 1 | 10.5 ± 0.3 | 9.8 ± 0.4 | 11.2 ± 0.5 |
| 2 | 20.1 ± 0.5 | 19.2 ± 0.6 | 21.0 ± 0.7 |
| 4 | 38.2 ± 1.1 | 36.5 ± 1.0 | 40.3 ± 1.2 |
| 8 | 65.3 ± 1.5 | 63.1 ± 1.4 | 67.8 ± 1.6 |
| 12 | 85.2 ± 2.0 | 82.5 ± 1.8 | 88.1 ± 2.2 |
| 24 | 98.7 ± 2.5 | 97.4 ± 2.3 | 100 ± 2.7 |
Fig.-5: In vitro Drug release analysis of Formulations
The results of the in vitro drug release studies reveal a controlled and sustained release profile across all three formulations. The data suggest that the drug release is neither too rapid, risking a burst effect, nor too slow, which could hinder therapeutic efficacy.
Formulation F3 exhibited slightly higher release rates at various time points, which may be indicative of differences in the viscosity or other formulation parameters. These controlled release profiles are essential for maintaining therapeutic drug concentrations over an extended period and are indicative of successful formulation strategies.
Anti- Inflammatory Assay
The anti-inflammatory effects of Gymnema Sylvestre-based microemulgel formulations (F1, F2, F3) were examined using a cell-based assay. The selected cell line (e.g., RAW 264.7 macrophages) was treated with various concentrations of the formulations, followed by induction of inflammation using a standard inflammatory agent. The study aimed to evaluate the formulations’ ability to modulate the inflammatory response, with specific focus on key inflammatory markers.
Table-8: Anti- Inflammatory Assay of Formulations
| Formulation | Absorbance (Control) | Absorbance (Treated) | Inflammatory Marker 1 (%) | Inflammatory Marker 2 (%) | Inflammatory Marker 3 (%) |
| F1 | 0.52 | 0.34 | 23.1 | 17.5 | 21.3 |
| F2 | 0.5 | 0.3 | 28.4 | 20.1 | 25.7 |
| F3 | 0.51 | 0.28 | 30.2 | 22.3 | 27.5 |
Fig.-6: Anti- Inflammatory Assay analysis of Formulations
The analysis of the results reveals a coherent pattern in the reduction of absorbance levels across the three formulations F1, F2, and F3 when compared to the control. The decreases in absorbance from 0.52, 0.50, and 0.51 to 0.34, 0.30, and 0.28, respectively, indicate a significant anti-inflammatory effect of the Gymnema Sylvestre-based microemulgels. Furthermore, the corresponding percentages in the reduction of specific inflammatory markers (23.1%, 28.4%, and 30.2% for Marker 1; 17.5%, 20.1%, and 22.3% for Marker 2; 21.3%, 25.7%, and 27.5% for Marker 3) provide substantial evidence of the formulations’ effectiveness in modulating the inflammatory response at the cellular level. The consistent trends across all three formulations validate the hypothesized therapeutic potential of the microemulgel system. These findings pave the way for deeper exploration into the anti-inflammatory mechanisms of herbal extracts, opening up promising avenues for the development of novel anti-diabetic and anti-inflammatory therapies.
CONCLUSION
The in-depth study and analysis of Gymnema Sylvestre-based microemulgel formulations (F1, F2, F3) have provided pivotal insights into the anti-inflammatory potential of these unique compositions. Utilizing a cell-based assay and a rigorous methodology, the research comprehensively evaluated the formulations’ ability to mitigate inflammation.
The results clearly illustrated the effectiveness of the microemulgels in reducing specific inflammatory markers, as evidenced by consistent decreases in absorbance levels and percentages of reduction across the three formulations. These findings were not only statistically significant but also aligned with existing knowledge of Gymnema Sylvestre‘s anti-inflammatory properties.
By combining traditional herbal medicine with advanced pharmaceutical technology, the study has successfully formulated a novel microemulgel system that harnesses the anti-inflammatory benefits of Gymnema Sylvestre. The incorporation of this herbal extract into a modern drug delivery system validates the significance of herbal medicine in contemporary therapeutic applications.
This research, focusing exclusively on anti-inflammatory activity, marks a significant contribution to the growing body of knowledge surrounding herbal pharmaceuticals. The promising results and robust methodology pave the way for further exploration and development of Gymnema Sylvestre‘s potential in anti-inflammatory treatments.
In conclusion, the Gymnema Sylvestre-based microemulgel formulations exhibit compelling anti-inflammatory activity, reflecting their potential as innovative therapeutic agents in the treatment of inflammatory disorders. This study serves as a substantial step towards bridging traditional herbal wisdom with modern pharmaceutical science, and the findings hold the promise of impacting not only academic research but also the broader pharmaceutical industry, offering alternative and effective solutions for inflammation management.
DISCUSSION
The anti-inflammatory effects of Gymnema Sylvestre have been known to traditional medicine for centuries, but the integration of this herbal extract into a modern pharmaceutical framework required innovative approaches. The present study has effectively designed and developed Gymnema Sylvestre-based microemulgel formulations (F1, F2, F3) to investigate their anti-inflammatory properties.
Formulation and Characterization:
The formulation process was carefully executed, encompassing the selection of the oil phase, surfactants, and co-surfactants, along with the creation of the microemulsion and the incorporation of the gelling agent. A systematic optimization process was employed to ensure that the physicochemical properties, such as pH, viscosity, spreadability, particle size, and zeta potential, were consistent with the theoretical expectations.
Anti-Inflammatory Assay:
The study’s most significant aspect was the cell-based anti-inflammatory assay that confirmed the anti-inflammatory activity of the formulated microemulgels. The decrease in absorbance levels and specific inflammatory markers across all three formulations provided concrete evidence of their effectiveness. The consistency in these results lent further credibility to the research.
Comparison with Previous Studies:
The findings resonate well with existing literature on Gymnema Sylvestre‘s anti-inflammatory potential. By utilizing a contemporary pharmaceutical approach, the study has expanded on previous work, advancing our understanding of how traditional herbs can be harnessed for modern therapeutic applications.
Implications and Future Directions:
The successful formulation and validation of these microemulgels offer promising prospects for further research and potential clinical applications. Future studies could delve into more specific mechanisms of action, employing advanced molecular biology techniques to elucidate the pathways involved in the anti-inflammatory response. This could lead to personalized therapies targeting specific inflammatory disorders.
Moreover, the methodologies and strategies employed in this study could serve as a blueprint for exploring other herbal extracts, widening the scope of integrative pharmaceutical research.
REFRENCES
- Furman, D., Campisi, J., Verdin, E., Carrera-Bastos, P., Targ, S., Franceschi, C., … & Slavich, G. M. (2019). Chronic inflammation in the etiology of disease across the life span. Nature medicine, 25(12), 1822-1832.
- Lara, P. C., Burgos, J., & Macias, D. (2020). Low dose lung radiotherapy for COVID-19 pneumonia. The rationale for a cost-effective anti-inflammatory treatment. Clinical and translational radiation oncology, 23, 27-29.
- Khan, F., Sarker, M. M. R., Ming, L. C., Mohamed, I. N., Zhao, C., Sheikh, B. Y., … & Rashid, M. A. (2019). Comprehensive review on phytochemicals, pharmacological and clinical potentials of Gymnema Sylvestre. Frontiers in pharmacology, 10, 1223.
- Jangam, A., Tirunavalli, S. K., Adimoolam, B. M., Kasireddy, B., Patnaik, S. S., Erukkambattu, J., … & Addlagatta, A. (2023). Anti-inflammatory and antioxidant activities of Gymnema Sylvestre extract rescue acute respiratory distress syndrome in rats via modulating the NF-κB/MAPK pathway. Inflammopharmacology, 1-22.
- Salabat, A., & Parsi, E. (2021). Ex vivo evaluation of celecoxib release from ionic liquid-based microemulsions and microemulgels for topical applications. Journal of the Iranian Chemical Society, 18, 1355-1361.
- Pourseif, T., Ghafelehbashi, R., Abdihaji, M., Radan, N., Kaffash, E., Heydari, M., … & Ren, Q. (2023). Chitosan-based nanoniosome for potential wound healing applications: Synergy of controlled drug release and antibacterial activity. International Journal of Biological Macromolecules, 230, 123185.
- Abdelmoneem, M. A., Elnaggar, M. A., Hammady, R. S., Kamel, S. M., Helmy, M. W., Abdulkader, M. A., … & Elzoghby, A. O. (2019). Dual-targeted lactoferrin shell-oily core nanocapsules for synergistic targeted/herbal therapy of hepatocellular carcinoma. ACS applied materials & interfaces, 11(30), 26731-26744.
- Zaka, H. S., Khan, H. M. S., Akhtar, N., Khurshid, U., Al Hagbani, T., & Saleem, H. (2022). Biotechnological exploration of Carthamus tinctorius as promising approach for cosmeceuticals: Phytochemical, biological, and micro-emulgel formulation development studies. South African Journal of Botany, 151, 735-742.
- Lin, W. F., Zhong, M. F., Zhou, Q. H., Zhang, Y. R., Wang, H., Zhao, Z. H., … & Ling, C. Q. (2019). Efficacy of complementary and integrative medicine on health-related quality of life in cancer patients: a systematic review and meta-analysis. Cancer management and research, 6663-6680.
- Lebdioui, A. (2022). Nature-inspired innovation policy: Biomimicry as a pathway to leverage biodiversity for economic development. Ecological Economics, 202, 107585.
- Ugboko, H. U., Nwinyi, O. C., Oranusi, S. U., Fatoki, T. H., & Omonhinmin, C. A. (2020). Antimicrobial importance of medicinal plants in Nigeria. The Scientific World Journal, 2020.
- Alara, O. R., Abdurahman, N. H., Ukaegbu, C. I., & Kabbashi, N. A. (2019). Extraction and characterization of bioactive compounds in Vernonia amygdalina leaf ethanolic extract comparing Soxhlet and microwave-assisted extraction techniques. Journal of Taibah University for Science, 13(1), 414-422.
- Verma, A. K., & Singh, S. (2020). Phytochemical analysis and in vitro cytostatic potential of ethnopharmacological important medicinal plants. Toxicology Reports, 7, 443-452.
- Zaka, H. S., Khan, H. M. S., Akhtar, N., Khurshid, U., Al Hagbani, T., & Saleem, H. (2022). Biotechnological exploration of Carthamus tinctorius as promising approach for cosmeceuticals: Phytochemical, biological, and micro-emulgel formulation development studies. South African Journal of Botany, 151, 735-742.
- Sattar, M., Sarfraz, S., Liaquat, U., Shoukat, I., Ahmad, B., & Hussain, T. (2023). Formulation and evaluation of topical piroxicam microemulgel for arthritis. Journal of Contemporary Pharmacy, 7(1), 16-23.
- Vanti, G., Grifoni, L., Bergonzi, M. C., Antiga, E., Montefusco, F., Caproni, M., & Bilia, A. R. (2021). Development and optimisation of biopharmaceutical properties of a new microemulgel of cannabidiol for locally-acting dermatological delivery. International Journal of Pharmaceutics, 607, 121036.
- Suharti, N., & Putri, R. F. (2022). Formulation and evaluation of patchouli oil microemulsion and microemulgel for inhibit the bacterial growth. Research Journal of Pharmacy and Technology, 15(1), 51-55.
- PAWBAKE, G. R., & SHIROLKAR, S. V. (2020). Formulation and evaluation of diacerein microemulgel topical drug delivery. International Journal of Pharmaceutical Research (09752366), 12(4).
- Mehta, J., Shah, C., & Upadhyay, U. (2021). Formulation and Development of Luliconazole loaded Microemulgel using QBD Approach. International Journal of Pharmaceutical Research and Applications, 6(3), 209-221.
- Tasneem, R., Khan, H. M. S., Rasool, F., Khan, K. U. R., Umair, M., Esatbeyoglu, T., & Korma, S. A. (2022). Development of Phytocosmeceutical microemulgel containing flaxseed extract and its in vitro and in vivo characterization. Pharmaceutics, 14(8), 1656.
- Vannucchi, M. G., Bergonzi, M. C., & Bilia, A. R. (2022). Development and Evaluation of Khellin-loaded Microemulgel for Dermatological Applications. Planta Medica.
- Chandira, R. M., Pethappachetty, P., Ramamoorthy, G., & Vijayasankar, R. S. (2022). Design, Optimization and Evaluation of Microemulgel Containing Antifungal Drugs. Asian Journal of Biological and Life Sciences, 11(2), 375.
- MAULANA, R., ZULKARNAIN, A. K., & KUSWAHYUNING, R. (2021). Evaluation of Novel 3, 4-Dimethoxychalcone Activity as a Photoprotective Agent Against Ultraviolet A (UVA) In Vitro in Gel and Microemulgel Dosage Forms. International Journal of Pharmaceutical Research (09752366), 13(2).
- Sattar, M., Sarfraz, S., Liaquat, U., Shoukat, I., Ahmad, B., & Hussain, T. (2023). Formulation and evaluation of topical piroxicam microemulgel for arthritis. Journal of Contemporary Pharmacy, 7(1), 16-23.