INTRODUCTION:

Oral administration of a drug is often considered as most efficient method for patients. However, due to variability in pH, motility; and enzyme activity, oral drugs are subjected to different physiological conditions in the stomach, small intestine, and large intestine¹.

There is a wide range of drug substances available in the field of developing pharmaceutical products, including latent candidates for drugs, which are frequently restricted by their poor solubility and permeability in aqueous media. Consequently, one of the greatest challenges of development of formulation is drug having limited solubility and permeability^2,3. Drugs with low solubility are classified as either BCS class II or BCS class IV under the Biopharmaceutics Classification System (BCS)^4,5.

The limited water solubility of a drug blocks its absorption since optimal absorption necessitates the drug to be dissolved, making it an essential requirement for achieving favorable oral bioavailability. It is worth noting that more than 40% of currently marketed formulations and 75% of compounds in development exhibit poor solubility and permeability in water. Consequently, this issue of low solubility and permeability continues to present an obstacle for achieving effective drug bioavailability and slow down novel drug development efforts^6.7. Thus, obtaining the right drug concentration at the right place is a major difficulty that formulation and development professionals frequently face^8,9. The number of techniques, such as solid dispersion, cyclodextrin complexation, lipid-based compositions, selfmicroemulsifying (SMEDDS) and self-nano emulsifying drug delivery system (SNEDDS), are as solutions for solubility and permeability problems^10,11.

Among them, The Self-nano emulsifying (SNEDDS) stands out as an effective technique for improving permeability and solubility. SNEDDS improves solubility and maintains the drug in a soluble condition, helping it pass through the gastrointestinal tract more easily and enhancing poorly soluble drug’s oral bioavailability^12-14. This system consists of heterogeneous distributions of two immiscible liquids, with droplets averaging in the nanometric scale which is not more than 100 nm in size^15-18. SNEDDS can be encapsulated into solid forms such as granules, pellets, and powders using various techniques, including supercritical fluid-based processes, molten granulation, and spray drying¹⁹. Each technique requires careful selection of excipients and carriers to preserve self-emulsifying properties. Research highlights the benefits of converting liquid SNEDDS (L-SNEDDS) to solid SNEDDS (S-SNEDDS), with adsorption on microporous interfaces being particularly efficient. The most studied method for achieving solid SNEDDS involves adsorption onto solid carriers with high porosity or specific surface area.

METHODS AND MATERIALS:

Materials:

Mesalamine was kindly gifted by Cipla Ltd., Mumbai. Ethyl oleate, Castor oil, Oleic acid, Isopropyl myristate, Olive oil, Span 20, Span 80, Tween 20, Tween 60, Tween 80, PEG 200, PEG 400, PEG 600, Propylene glycol was provided by Loba Chemie Pvt. Ltd., Mumbai. Fujicalin and Neusilin US2 was provided by Gangwal Chemicals, Mumbai and Aerosil 200 was provided by Molychem Pharma, Mumbai. All other chemicals used for analysis were of analytical grades.

Solubility studies:

The saturation solubility of mesalamine was studied in various oils, surfactants; and co-surfactants. This research aimed to identify solvents with high solubilizing capacity for mesalamine. The excess mesalamine was combined with the 5mL of each solvent in a vial, vortexed for 72h at room temperature. After that, the mixtures were filtered and centrifuged for 15 min. at 2000rpm. A UV spectrophotometer was used to measure the quantity of mesalamine in the supernatant at λmax 236nm, with 0.1 N HCL as the blank solution. To ensure accuracy, each measurement was carried out three times¹⁵.

Screening of surfactant and co-surfactant:

The shake flask method was used to determine the solubility of mesalamine in different surfactants and co-surfactants at room temperature. The evaluation was done by using of co-surfactants propylene glycol and PEG 200, PEG 400, PEG 600, and surfactants Tween 20, Tween 60, Tween 80, and Span 20. In every time, 10 mg of mesalamine and 10mL of the respective surfactant or co-surfactant were combined into a vial. The vials were incubated at 37±0.5°C for 23h, followed by an additional 12h equilibration at the same temperature. After filtration, the resulting solutions were analyzed at 275nm using a UV spectrophotometer. The quantity of dissolved mesalamine was determined using calibration curve. This process was repeated until the desired concentration of mesalamine was achieved.

Construction of ternary phase diagram:

Based on solubility and emulsification tests, Tween 80, oleic acid, and PEG 200 have been selected as the surfactant, oil, and co-surfactant, respectively. In order to identify self-emulsifying regions involving different volume ratios of surfactant and co-surfactant (1:1, 2:1, 3:1) in combination with oil, a pseudoternary phase diagram was constructed using the water titration method. These mixtures were titrated with water while being gently stirred, observing the clarity to distinguish between regular emulsions (turbid) and nanoemulsions (clear). The optimal ratios for SNEDDS formulation were recorded. The phase diagram, constructed using CHEMIX School software, visually represents the relationships between water, oil, and the surfactant-co-surfactant mixture, providing insights into binary mixtures of the components¹⁶.

Preparation of Mesalamine loaded L-SNEDDS:

The Km value indicating a wide nanoemulsion region was chosen from the phase diagrams for further study. Three formulations were selected, with their water, oil, and Smix concentrations calculated. Mesalamine (60 mg) was dispersed in oil and mixed with Smix to form a homogenous compound. The formulations were stored at 25°C in glass containers for stability testing. The formulations were optimized using a 3-factor, 3-level Box-Behnken design and Response Surface Methodology (RSM). The ranges for Tween (X2), PEG 200 (X3), and Oleic acid (X1) are shown in a ternary phase diagram. The optimization analyzed the impacts, interactions, and quadratic effects of these components. The study focused on globule size (Y1), % transmittance (Y2), and drug entrapment (Y3) as dependent variables, aiming to minimize globule size and polydispersity index to enhance solubility and drug release.

Characterization of L-SNEDDS:

Thermodynamic stability studies:

Three different tests were conducted on the prepared L-SNEDDS with the objective to evaluate the thermodynamic stability evaluation. Formulations were centrifuged for 30min. at 5000rpm in the centrifugation analysis, and any indications of instability were visually assessed. The stable formulations were then heated to 45°C and cooled to 4°C for six cycles, with a 48h rest period in between. In a freeze-thaw cycle, that involved three cycles of temperatures that varied between -20°C and +25°C with 48h of storage at each temperature, compositions that remained stable were studied.^17,18.

Robustness to dilution:

The robustness of Mesalamine SNEDDS was evaluated by diluting them 50, 100, and 1000 times with various diluents, such as double-distilled water and phosphate buffer (pH 7.4). Alteration, including phase segregation or drug sedimentation, were evaluated and documented in diluted samples over the course of a day.

Percentage transmittance (%T):

The procedure involved diluting 1mL of liquid SNEDDS with 100mL of distilled water, checking for turbidity, and ensuring the % transmittance at 206nm by utilizing a UV spectrophotometer. This step helps determine the optical clarity of the SNEDDS formulations after dilution, which is indicative of their isotropic parameter.

Globule size analysis, PDI, Zeta potential, and Viscosity:

The mesalamine L-SNEDDS formulations were diluted and analyzed for globule size using a dynamic laser diffraction particle size analyzer. Zeta potential was measured using a Zeta sizer with a He-Ne red laser, after diluting the formulation with double-distilled water¹⁹. Measurements were taken at 25°C. Each formulation batches viscosity were determined at 20rpm by using Brookfield viscometer containing a spindle S21. Simulated gastric fluid (SGF) and 10mL of L-SNEDDS were combined, agitated, and the volume was subsequently raised to 100mL for drug entrapment. A calibration curve was used to measure the UV absorbance of the diluted solution at 206nm in order to identify the drug concentration.

In vitro permeation of L-SNEDDS:

A Franz diffusion cell with a 22mL receptor compartment and a 0.4µm cellulose acetate membrane separate it from the donor compartment was used for in vitro drug release study. The membrane was treated with L-SNEDDS. In that order, 0.1N HCL, pH 6.4 phosphate buffer, and pH 7.2 phosphate buffer were added to the receptor compartment. The setup was kept at 37±0.5°C and placed on the hot plate magnetic stirrer at 50rpm. At intervals of 2h, 2mL samples were obtained and replaced with new medium (pH 6.4 buffer for 1h, pH 7.2 buffer for 8h, and 0.1N HCL for the first 2h). Air bubbles were monitored and removed during sampling, and the receptor compartment was refilled after each sample withdrawal.

Preparation of Mesalamine loaded S-SNEDDS:

The improved L-SNEDDS have been transformed into a solid state by an adsorption technique in order to make use of the benefits of solid dosage forms as a free-flowing powder. To put it simply, a porcelain dish was filled with the solid adsorbent carrier Aerosil 200, and drops at a time, optimal mesalamine-loaded L-SNEDDS was added. The mixture was gradually mixed until a powder with appropriate flow characteristics was obtained. After that, the freely-flowing powder was put into size 2 hard gelatin capsules and kept there till for further studies.

Characterization of S-SNEDDS:

Solubility:

The solubility of solid-SNEDDS was assessed in Oleic acid, Tween 80, and PEG 200 due to the drug's poor aqueous solubility. Following appropriate dilution, the solid-SNEDDS powder was appropriately diluted and then placed in orbital shaker for 72h. Solubility assessment of the resulting mixture was conducted via UV spectroscopy set to 215nm.

Flow property of S-SNEDDS:

The flow properties of powders were evaluated using several methods. The angle of repose was measured by allowing powder to flow through a fixed funnel, forming a heap, and calculating the angle between the heap and the base using the formula . While tapped density involves tapping the powder in a graduated cylinder to establish the same volume before calculating the density, bulk density was determined by dividing the powder's weight by its volume. Hausner's ratio, which shows flow characteristics, was calculated from the ratio of tapped to bulk density, and Carr's Compressibility Index (CCI) was generated using the difference between the tapped and bulk densities.

Powder X-ray Diffraction (PXRD):

The P-XRD patterns of mesalamine; and optimized mesalamine-loaded S-SNEDDS were recorded using X-ray diffractometer (Model-D8. Advance, Bruker Germany). At a pace of 10° per minute, samples were scanned for 2θ values ranging from 5 to 45°.

Differential Scanning Calorimetry (DSC):

A differential scanning calorimeter (TA Instruments Trios V5.4.0.300) was utilized for recording the mesalamine DSC thermogram and the optimized mesalamine-loaded S-SNEDDS. The powdered samples were tightly sealed in aluminum pans and heated at a constant rate of 10°C/min. within the temperature range of 35°C to 350°C.

Field Emission Scanning Electron Microscopy (FE-SEM):

The morphology of mesalamine-loaded SNEDDS was observed by FE-SEM (Thermos Fisher Scientific model ApreSLoVac). It employs electron emitters from a field emission source, which can emit electron up to 1000 times more than those from a tungsten filament, necessitating a higher degree of vacuum.

RESULT AND DISCUSSION:

Solubility studies:

The saturation solubility study was revealed that Oleic acid (17.76mg/ml), Tween 80(41mg/ml), and PEG 200 (77.52mg/ml) demonstrated high solubility for Mesalamine and were chosen for the Mesalamine liquid nanoemulsion formulation.

Construction of Pseudo ternary phase diagram:

Figure 1: Pseudo ternary phase diagram of Oleic acid, Tween 80, and PEG 200.

The phase diagram for Km = 3 was derived from three pseudo-ternary phase diagrams. Compared to the Km values of 1 and 2, Km = 3 shows a larger and more effective nanoemulsion region. Consequently, the liquid nanoemulsion and the subsequent solid SNEDDS formulation were selected based on the Km = 3 phase diagram shown in fig.1.

Figure 2: Selected composition of SNEDDS Km=3

The three formulations designated M1, M2, and M3, were selected from the phase diagram at a Km value of 3, as shown in Fig 2. To characterize the nanoemulsion in its liquid state, the chosen composition from the phase diagram was prepared using titration with distilled water.

Table 1: Optimization of L-SNEDDS formulation

Run	Amount of Tween 80 (%)	Amount of PEG 200 (%)	Amount of Oleic acid (%)	% Transmittance	Globule size	% Drug Entrapment
1	22.5	7.50	10	77.57	852.5	89.10
2	18.75	7.50	15	43.74	1180.1	88.40
3	26.25	8.75	10	89.57	567.2	97.87
4	22.5	7.50	10	77.57	966.8	91.24
5	22.5	8.75	15	65.44	481.7	94.77
6	18.75	7.50	05	93.60	692.8	92.44
7	18.75	6.25	10	63.76	578.5	92.83
8	26.25	7.50	15	80.69	321.3	97.03
9	22.5	6.25	05	92.71	267.4	94.32
10	26.25	7.50	05	96.03	791.3	96.68
11	22.5	7.50	10	77.57	866.8	87.40
12	22.5	6.25	15	60.74	565.6	93.51
13	26.25	6.25	10	91.88	258.5	95.12
14	22.5	8.75	05	95.49	414.8	98.24
15	18.75	8.75	10	78.27	901.7	93.01

Desirability function:

This formulation achieved a comprehensive desirability score of 0.952, approaching unity, indicating successful alignment with the specified constraints. A lower desirability score implies suboptimal outcomes, while a higher score, closer to one, signifies greater accuracy in achieving the defined objective. This underscores the effectiveness and rationality of the optimization process, as the formulation closely aligns with the anticipated results. The optimized batch derived from Design of Experiments (DoE) was subsequently produced and utilized for further characterization Desirability function given by DoE shown in table 2.

Table 2: Desirability function given by DoE

Parameter	Desirability	Predicted Value	Actual Value
% Transmittance	0.952	99.55	95.49
Globule size		134.34	107.3
% Drug Entrapment		97.23	93.94

Evaluation of L-SNEDDS:

Thermodynamics stability studies:

A nanoemulsion, created with specific proportions of oil, co-surfactant, water, and surfactant, is thermodynamically stable without phase separation, cracking, or creaming. Physical instability can affect performance and cause phase separation, so thermodynamic stability was tested using heating-cooling cycles, centrifugation, and freeze-thaw cycles. Results showed in water and oil ratios were stable, shown in table 3.

Robustness to dilution:

The study showed no signs of phase separation or drug precipitation upon dilution.

Dispersibility or Self-emulsification test:

Using a standard USP II dissolution apparatus, the self-emulsification efficacy of the oral liquid Nano-emulsion was evaluated. All formulations quickly formed a slightly less transparent, slightly yellowish-white emulsion, receiving a grade A, indicating strong self-nanoemulsifying capacity.

% Transmittance, Globule size, PDI, Zeta potential, Viscosity and Drug entrapment:

The results for % transmittance, globule size, PDI, zeta potential, viscosity and drug entrapment are summarized in table 4. The % transmittance of all L-SNEDDS formulations of Mesalamine ranged from 60.74 to 96.03, indicating that the prepared SNEDDS are clear and not turbid.

Table 3: Thermodynamics stability studies, robust to dilution and dispersibility tests

Formulation	Observations					Inference
Formulation	Heating cooling cycle	Centrifugation test	Freeze thaw cycle	Robustness to dilution	Dispersibility test (Grade)	Inference
M1	✓	✓	✓	✓	A	Passes
M2	✓	✓	✓	✓	A	Passes
M3	✓	✓	✓	✓	A	Passes
M4	✓	✓	✓	✓	A	Passes
M5	✓	✓	✓	✓	A	Passes
M6	✓	✓	✓	✓	A	Passes
M7	✓	✓	✓	✓	A	Passes
M8	✓	✓	✓	✓	A	Passes
M9	✓	✓	✓	✓	A	Passes
M10	✓	✓	✓	✓	A	Passes
M11	✓	✓	✓	✓	A	Passes
M12	✓	✓	✓	✓	A	Passes
M13	✓	✓	✓	✓	A	Passes
M14	✓	✓	✓	✓	A	Passes
M15	✓	✓	✓	✓	A	Passes

Table 4: Result of % Transmittance, Globule size, Zeta potential, PDI, and Viscosity:

Formulation	% Transmittance	Globule size	Zeta potential	PDI	Viscosity	Drug Entrapment
M1	77.57	852.5	-34.6	0.553	22.57	89.1
M2	43.74	1180.1	-29.8	0.856	20.42	88.4
M3	89.57	567.2	-23.4	0.412	21.04	97.87
M4	77.57	966.8	-33.5	0.331	18.48	91.24
M5	65.44	481.7	-34.2	0.576	17.65	94.77
M6	93.60	692.8	-35.6	0.764	21.02	92.44
M7	63.76	578.5	-33.1	0.618	19.98	92.83
M8	80.69	321.3	-42.5	0.491	19.85	97.03
M9	92.71	267.4	-44.7	0.559	22.34	94.32
M10	96.03	791.3	-36.4	0.373	18.95	96.68
M11	77.57	866.8	-36.8	0.656	17.24	87.40
M12	60.74	565.6	-35.4	0.358	20.51	93.51
M13	91.88	258.5	-46.8	0.459	21.98	95.12
M14	95.49	414.8	-48.2	0.582	19.69	98.24
M15	78.27	901.7	-51.7	0.643	22.14	93.01

Cloud point measurement:

All liquid SNEDDS tested had cloud points greater than 78°C, indicating that the nanoemulsions will remain stable at physiological temperatures without concerns of phase separation.

In vitro permeation of L-SNEDDS:

The in-vitro diffusion study was conducted using a Franz diffusion apparatus. The diffusion comparison of the plain drug and the liquid SNEDDS formulation batch of Mesalamine in different diffusion media (0.1N HCL, phosphate buffer pH 6.4, and phosphate buffer pH 7.2) is shown in fig. 3 and table 5.

Figure 3: % CDR of optimized batch and Mesalamine pure drug

Table 5: Comparison of flux of optimized batch and Mesalamine pure drug

Sr. No	Samples	Flux (µg/cm²/h)
1	Mesalamine	2.853
2	Optimized batch	4.063

Formulation and Characterization of S-SNEDDS:

Micromeritic properties of S-SNEDDS:

The results of this research demonstrate that the drugs concentration and flow properties of all S-SNEDDS formulations are excellent. Good flow characteristics were shown by the final optimized batch's angle of repose, was a 32.61°, bulk density was 0.288 g/mL and the tapped density was 0.355g/mL respectively. Hausner's ratio was found to be 1.23 and Carr's index to be 20%.

Solubility Study:

Three components were found to be soluble in the Mesalamine s-SNEDDS premix: oleic acid (oil), Tween 80 (surfactant), and PEG 200 (co-surfactant). This was determined by mixing Tween 80, PEG 200, and oleic acid in vials using Mesalamine s-SNEDDS. Following this, the vials were kept for 72h in an orbital shaker. After this period, the premix was analyzed using a UV spectrometer to observe the solubility of the prepared Mesalamine s-SNEDDS, which showed enhanced solubility compared to the pure drug Mesalamine.

Reconstitution properties of S-SNEDDS:

Globule size, PDI, and Zeta potential:

The rate and extent of drug release absorption is determined by the size of the globule. The average droplet size of mesalamine-loaded SNEDDS was determined to be 107.3nm, with a PDI of 0.365, indicating that the globule size was uniform. Increasing the Smix amount was observed to reduce the average globule size. Mesalamine-loaded SNEDDS have been found to have a zeta potential of -17.7 mV. Zeta potential values in the -20mV to -30mV range for both charges indicate that the system is stable, shown in fig.4.

Figure 4: Globule size, PDI, and Zeta potential of S-SNEDDs

Solid state characteristics of S-SNEDDS:

Powder X-ray Diffraction Studies:

XRD was conducted to investigate the polymorphic state of Mesalamine SNEDDS, specifically to determine whether it exists in an amorphous or crystalline form. The XRD spectra of pure Mesalamine displayed multiple peaks characteristic of its crystalline nature. However, peaks were absent in the diffractogram of the Mesalamine SNEDDS, indicating complete amorphization of Mesalamine within S-SNEDDS formulation shown in fig. 5(a) and (b).

Figure 5: XRD of Mesalamine (a) and Mesalamine-loaded S-SNEDDS (b)

Differential Scanning Colorimetry:

The optimized Mesalamine S-SNEDDS formulation was observed at 84.90°C, as shown in fig 6 (a) and (b). This indicates a shift in the melting endotherm of Mesalamine, suggesting amorphous precipitation of the drug and better solubilization in the carrier. Consequently, Mesalamine loses its crystalline nature and converts to an amorphous form.

Figure 6: DSC thermogram of Mesalamine (a) and Mesalamine S-SNEDDS formulation(b)

Morphological analysis of S-SNEDDS:

Field emission scanning electron microscopy (FESEM) was used to analyze the morphology of the optimized batch. The micrographs revealed that the drug is entirely dissolved within the S-SNEDDS shown in fig. 7

Figure 7: FE-SEM of optimized formulation

Development of oral dosage form:

Filling of capsule:

60mg of equivalent Mesalamine was filled into hard gelatin capsule and characteristics were carried out.

Characteristics of solid dosage form:

Weight variation was found to be 1.20% which was within I.P limits i.e. >7.5% , The disintegration time for the development of capsules was found to be 4 ± 0.5 min and was within the I.P limit i.e. > 15 min

In-vitro dissolution study:

A USP type II instruments was used to carry out the in-vitro dissolution study. Fig. 8 shows the dissolution of the mesalamine drug and solid SNEDDS formulation batch in three different dissolution media: pH 6.4, pH 7.2, and 0.1N HCl.

Figure 8: %CDR of optimized batch and Pure drug

CONCLUSION:

The successfully developed and evaluated a Solid self-nanoemulsifying drug delivery system (SNEDDS) for Mesalamine, confirming its purity and properties through various characterization technique. Solubility studies identified oleic acid, Tween 80, and PEG 200 as the most effective components. Using a pseudoternary phase diagram and Box Behnken design, an optimal liquid SNEDDS was formulated with globule size of 107 nm and a zeta potential of -17 mV. This was converted to solid SNEDDS using Aerosil 200, undergoing extensive physical and chemical evaluations. In vitro dissolution showed a higher drug release rate for s-SNEDDS compared to pure drug Mesalamine, and stability tests indicated no significant changes in appearance or drug content, with a minor acceptable increase in particle size. Overall, s-SNEDDS enhanced Mesalamine’s solubility, absorption, and permeability, indicating improved drug delivery and therapeutic efficacy.

ACKNOWLEDGEMENTS:

I would like to express my gratitude to my mentor, Dr. Anilkumar J. Shinde, Associate Professor in the Pharmaceutics Department at Bharati Vidyapeeth College of Pharmacy in Kolhapur, for his invaluable time, superb leadership, careful supervision, encouragement, and constant motivation. Additionally, I am appreciating to Dr. H. N. More, Principal of Bharati Vidyapeeth College of Pharmacy in Kolhapur, for providing first-rate workspace for this project.

CONFLICT OF INTEREST:

The authors declared no conflict of interest.

AUTHOR CONTRIBUTIONS:

The experiment was planned, carried out, and data was evaluated by the author, who also wrote the manuscript. Each author contributed equally to the completion of this study.

REFERENCES:

1. Abboudi, Z. H., et al. Fatal aplastic anaemia after Mesalazine. The Lancet 343.8896 (1994): 542. doi.org/10.1016/S0140-6736(94)91495-8.

2. Hiral A. Makadia, Ami Y. Bhatt, Ramesh B. Parmar, Ms. Jalpa S. Paun, H.M. Tank. Self-nano Emulsifying Drug Delivery System (SNEDDS): Future Aspects. Asian J. Pharm. Res. 2013; 3(1):20-26.

3. Avijeet J. Zalte, Rajendra K. Surawase. Formulation and Characterization of Colon Targeted Mesalamine Pellets. Asian J. Pharm. Res. 2024; 14(2): 107-13.

4. O.M. Bagade, D.R. Kad, D.N. Bhargude, D.R. Bhosale and S.K. Kahane. Consequences and Impose of Solubility Enhancement of Poorly Water Soluble Drugs. Research J. Pharm. and Tech. 2014; 7(5): 598-607.

5. AV Yadav, VB Yadav. Improvement of Physicochemical properties of Mesalamine with Hydrophilic Carriers by Solid Dispersion (kneading) method. Research J. Pharm. and Tech. 2008; 1(4): Oct.-Dec. 422-425.

6. Pratiksha Sonawale, Amol Patil, Asmit Kamble, Mangesh Bhutkar. Solubility Enhancement of Lipophilic Drugs - Solid Self Micro-Emulsifying Drug Delivery System. Asian J. Pharm. Tech. 2016; 6 (3): 155-158.

7. Hiral A. Makadia, Ami Y. Bhatt, Ramesh B. Parmar, Ms. Jalpa S. Paun, H.M. Tank. Self-nano Emulsifying Drug Delivery System (SNEDDS): Future Aspects. Asian J. Pharm. Res. 2013; 3(1): 20-26.

8. Avijeet J. Zalte, Rajendra K. Surawase. Formulation and Characterization of Colon Targeted Mesalamine Pellets. Asian J. Pharm. Res. 2024; 14(2): 107-3.

9. M. Surendra, T. Venkateswara Rao, K. Lokeswara Reddy, A. Ramesh Babu. Formulation and Evaluation of Mucoadhesive Microcapsules of Aceclofenac for Oral controlled release by Emulsification-gelation Technique. Research J. Pharm. and Tech. 2012; 5(4): 525-532.

10. Deepak Patel, Sunil Kumar Shah, Chandra Kishore Tyagi. Design, Formulation and Characterization of Microspheres containing Mesalamine for the Treatment of Ulcerative Colitis. Research Journal of Science and Technology. 2021; 13(3): 165-9.

11. S. Sudarshan, S. Sangeeta, NR Sheth, P. Roshan, YV Ushir, R. Gendle. Colon Specific Drug Delivery System of Mesalamine for Eradication of Ulcerative Colitis. Research J. Pharm. and Tech. 2009; 2(4): 819-823.

12. P. B. Patil, A. A. Hajare, R. P. Awale. Development and Evaluation of Mesalamine Tablet Formulation for Colon Delivery. Research J. Pharm. and Tech. 2011; 4(11): 1751-1756.

13. Akshay D. Patil, Swapnil V. Patil, Kishor S. Salunkhe, S. R. Chaudhari. Review on: Importance and Methods of Reduction of Water Solubility and Swelling of Natural Polysaccharide Polymer for Colon specific Drug Delivery System. Research J. Pharm. and Tech. 2013; 6(5): 447-453.

14. Pramod Salve. Optimization of aqueous based film coating technique for pellets in colon specific delivery of mesalamine . Research J. Science and Tech. 2011; 3(5): 238-246.

15. Craig, D. Q. M., et al. "An investigation into the mechanisms of self-emulsification using particle size analysis and low frequency dielectric spectroscopy." International Journal of Pharmaceutics. 1995; 114(1): 103-110. doi.org/10.1016/0378-5173(94)00222-Q

16. RJ Garala, SV Shirolkar, AD Deshpande, AD Kulkarni. Colon Targeted Drug Delivery System of Prednisolone by Press Coating Technique: Effect of Different Grades of Hydroxyethylcellulose in Coat. Research J. Pharm. and Tech. 2011; 4(3): 405-410.

17. Parmar, Nitin, et al. Study of cosurfactant effect on nanoemulsifying area and development of lercanidipine loaded (SNEDDS) self nanoemulsifying drug delivery system. Colloids and Surfaces B: Biointerfaces. 2011; 86(2): 327-338. doi.org/10.1016/j.colsurfb.2011.04.016

18. S. Sudarshan, S. Sangeeta, NR Sheth, P. Roshan, YV Ushir, R. Gendle. Colon Specific Drug Delivery System of Mesalamine for Eradication of Ulcerative Colitis. Research J. Pharm. and Tech. 2009; 2 (4): 819-823.

19. Rathore, Charul, et al. Self-nanoemulsifying drug delivery system (SNEDDS) mediated improved oral bioavailability of thymoquinone: optimization, characterization, pharmacokinetic, and hepatotoxicity studies. Drug Delivery and Translational Research. 2023; 13(1): 292-307. doi.org/10.1007/s13346-022-01193-8.

Received on 18.07.2024 Revised on 12.11.2024

Accepted on 14.01.2025 Published on 01.07.2025

Available online from July 05, 2025

Research J. Pharmacy and Technology. 2025;18(7):3228-3235.

DOI: 10.52711/0974-360X.2025.00464

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.