Development and Evaluation of Colon-Targeted Aspirin Tablets

Colon-targeted drug delivery systems are designed to deliver drugs specifically to the colon while minimizing premature release in the stomach and small intestine. This approach is useful for the treatment of local colonic disorders such as ulcerative colitis, Crohn’s disease, colorectal inflammation, and colorectal cancer-related conditions. Compared with conventional oral dosage forms, colon-targeted systems may improve therapeutic efficiency by increasing drug concentration at the desired site, reducing dose requirement, limiting systemic side effects, and protecting the drug from degradation in the upper gastrointestinal tract. Aspirin, also known as acetylsalicylic acid, is a widely used non-steroidal anti-inflammatory drug with analgesic, antipyretic, anti-inflammatory, and antiplatelet activities. It acts mainly by inhibiting cyclooxygenase enzymes and reducing prostaglandin synthesis. Although aspirin has therapeutic importance, its long-term oral administration is commonly associated with gastrointestinal irritation, ulceration, and bleeding. These adverse effects limit its use, especially when prolonged therapy is required. Therefore, developing a colon-targeted delivery system for aspirin may be a useful strategy to reduce drug exposure in the upper gastrointestinal tract and enhance local availability in the colon. The colon provides several physiological features that can be exploited for targeted delivery, including relatively higher pH, longer residence time, lower enzymatic activity compared with the upper intestine, and the presence of abundant colonic microflora. Various formulation approaches have been investigated for colon targeting, such as pH-dependent coating, time-dependent release systems, polysaccharide-based carriers, prodrug systems, microbially triggered delivery, matrix tablets, microspheres, nanoparticles, and multiparticulate systems. Among these, polymer-based and polysaccharide-based systems are especially promising because they can protect the drug during transit through the stomach and small intestine and release it after reaching the colonic environment. A colon-targeted aspirin formulation may offer advantages by delaying aspirin release until the dosage form reaches the colon, thereby reducing gastric irritation and improving site-specific drug action. Such a system may be developed using suitable polymers that remain stable in acidic gastric pH but dissolve, degrade, or swell under colonic conditions. Evaluation of the prepared system generally includes preformulation studies, drug–excipient compatibility, physicochemical characterization, in-vitro drug release studies in simulated gastrointestinal fluids, and assessment of release kinetics. The present research focuses on the preparation and evaluation of an aspirin colon-targeted drug delivery system. The main objective is to formulate a dosage form capable of protecting aspirin in the upper gastrointestinal tract and releasing it specifically in the colon. This work may contribute to the development of safer and more effective oral aspirin therapy for conditions where localized colonic delivery is desirable.

MATERIALS AND METHODS

MATERIALS

Aspirin was used as the active pharmaceutical ingredient. Crospovidone, croscarmellose sodium, and Kyron T-114 were employed as . Mannitol was used as the diluent, aspartame as the sweetening agent, talc as the glidant, and magnesium stearate as the lubricant. All chemicals and reagents used in the study were of analytical grade and used without further purification.

2.2 Preformulation Studies

Preformulation studies were carried out to determine the physicochemical characteristics of Aspirin prior to formulation development.

2.2.1 Organoleptic Evaluation

The drug powder was visually examined under white light for colour and appearance. Odour was assessed by gentle smelling, while texture and flow characteristics were evaluated manually by rubbing the powder between the fingers. These observations were used to assess the suitability of the drug for direct compression.

2.2.2 Solubility Study

The solubility of Aspirin was determined in distilled water, 0.1 N hydrochloric acid, phosphate buffer (pH 6.8), and simulated saliva. An excess quantity of the drug was added separately to 10 mL of each solvent in stoppered conical flasks. The suspensions were shaken intermittently and allowed to equilibrate at room temperature for 24 h. The solutions were filtered through a 0.45 µm membrane filter, suitably diluted, and analysed using a UV–Visible spectrophotometer. Solubility was expressed in mg/mL.

2.2.3 Melting Point Determination

The melting point was determined using the capillary method. Approximately 25–50 mg of Aspirin was filled into a sealed capillary tube and placed in a digital melting point apparatus. The temperature was increased gradually at a rate of 1–2°C/min near the expected melting range, and the temperatures corresponding to the onset and completion of melting were recorded.

2.2.4 UV Spectrophotometric Analysis

A standard stock solution of Aspirin (100 µg/mL) was prepared by dissolving 10 mg of drug in methanol and making the volume up to 100 mL. The solution was further diluted to obtain a working solution of 10 µg/mL, which was scanned over the wavelength range of 200–400 nm to determine the maximum absorption wavelength (λmax). Standard solutions of 2–10 µg/mL were prepared from the stock solution, and absorbance was measured at 282 nm. A calibration curve was constructed by plotting absorbance against concentration to verify Beer–Lambert's law.

2.2.5 Drug–Excipient Compatibility Study

Compatibility between Aspirin and selected excipients was evaluated using FTIR spectroscopy and Differential Scanning Calorimetry (DSC). For FTIR analysis, the drug and physical mixtures (1:1) with individual excipients were blended with dry potassium bromide and compressed into transparent pellets. The spectra were recorded over the range of 4000–400 cm⁻¹ and compared for changes in characteristic absorption peaks. For DSC analysis, approximately 5–10 mg of the drug and physical mixtures were sealed in aluminium pans and analysed over the temperature range of 30–300°C under a nitrogen atmosphere at a heating rate of 10°C/min. The thermograms were compared to detect any thermal incompatibility.

2.3 Experimental Design

A three-level full factorial design was employed using Design-Expert® software (Version 13.0.5.0) to optimize the formulation variables. Crospovidone (Factor A) and croscarmellose sodium (Factor B) were selected as independent variables, while tablet disintegration time and hardness were selected as dependent responses. A total of nine formulations were generated to evaluate the individual and interaction effects of both formulation variables.

2.4 Preparation of Aspirin Oral Tablets

Aspirin oral tablets were prepared by the direct compression method. All ingredients were accurately weighed according to the formulation design and passed through a 40-mesh sieve to obtain uniform particle size. Aspirin, crospovidone, croscarmellose sodium, Kyron T-114, mannitol, and aspartame were blended for approximately 10–15 min to obtain a homogeneous mixture. Talc was then added and mixed for 3–5 min, followed by magnesium stearate, which was blended gently for an additional 2–3 min to avoid over-lubrication. The final powder blend was compressed using a rotary tablet compression machine to obtain tablets of approximately 200 mg with adequate hardness and mechanical strength.

Figure. Calibration curve of Aspirin

Fig: Percentage Drug Release of Aspirin Formulations

Drug content analysis demonstrated satisfactory content uniformity among all formulations, with values ranging from 90.12% to 97.30%. The optimized formulation (F9) exhibited the highest drug content (97.30%), indicating efficient blending, uniform distribution of the active pharmaceutical ingredient, and minimal drug loss during processing. These findings confirm the suitability of the direct compression method for producing Aspirin oral tablets with acceptable pharmaceutical quality. Overall, formulation F9 exhibited the most desirable balance of mechanical strength, rapid disintegration, low friability, and high drug content, and was therefore selected as the optimized formulation for subsequent dissolution and stability studies.

CONCLUSION

The present study was carried out to formulate and evaluate an aspirin colon-targeted drug delivery system. All prepared formulations showed acceptable pre-compression and post-compression properties. The powder blends exhibited good flow characteristics, as indicated by suitable bulk density, tapped density, angle of repose, Carr’s Index, and Hausner’s ratio values. The prepared tablets also showed satisfactory physical properties, including uniform weight, acceptable thickness, adequate hardness, low friability, suitable disintegration time, and good drug content. Among all formulations, F9 was selected as the optimized formulation because it showed the most desirable evaluation results. F9 exhibited good flow property, lowest friability, acceptable hardness, shorter disintegration time, and highest drug content compared with other batches. These results indicate that the optimized formulation may be suitable for colon-targeted delivery of aspirin. The developed system may help to protect aspirin from early release in the upper gastrointestinal tract and promote drug release in the colon, thereby reducing gastric irritation and improving site-specific drug delivery. Therefore, it can be concluded that the aspirin colon-targeted formulation was successfully prepared and evaluated, and formulation F9 showed the best overall performance among all batches.

REFERENCES

1. Amidon, S., Brown, J. E., & Dave, V. S. (2015). Colon-targeted oral drug delivery systems: Design trends and approaches. AAPS PharmSciTech, 16(4), 731–741. https://doi.org/10.1208/s12249-015-0350-9
2. Aulton, M. E., & Taylor, K. M. G. (Eds.). (2018). Aulton’s pharmaceutics: The design and manufacture of medicines (5th ed.). Elsevier.
3. Awad, A., Madla, C. M., McCoubrey, L. E., Ferraro, F., Gavins, F. K. H., Buanz, A., Gaisford, S., Orlu, M., Siepmann, F., Siepmann, J., & Basit, A. W. (2022). Clinical translation of advanced colonic drug delivery technologies. Advanced Drug Delivery Reviews, 181, 114076. https://doi.org/10.1016/j.addr.2021.114076
4. Azehaf, H., Benzine, Y., Tagzirt, M., Skiba, M., & Karrout, Y. (2023). Microbiota-sensitive drug delivery systems based on natural polysaccharides for colon targeting. Drug Discovery Today, 28(7), 103606. https://doi.org/10.1016/j.drudis.2023.103606
5. Chourasia, M. K., & Jain, S. K. (2003). Pharmaceutical approaches to colon targeted drug delivery systems. Journal of Pharmacy & Pharmaceutical Sciences, 6(1), 33–66.
6. Gazzaniga, A., Moutaharrik, S., Filippin, I., Foppoli, A., Palugan, L., Maroni, A., & Cerea, M. (2022). Time-based formulation strategies for colon drug delivery. Pharmaceutics, 14(12), 2762. https://doi.org/10.3390/pharmaceutics14122762
7. Guirguis-Blake, J. M., Evans, C. V., Perdue, L. A., Bean, S. I., & Senger, C. A. (2022). Aspirin use to prevent cardiovascular disease and colorectal cancer: Updated evidence report and systematic review for the US Preventive Services Task Force. JAMA, 327(16), 1585–1597. https://doi.org/10.1001/jama.2022.3337
8. Huang, E. S., Strate, L. L., Ho, W. W., Lee, S. S., & Chan, A. T. (2011). Long-term use of aspirin and the risk of gastrointestinal bleeding. The American Journal of Medicine, 124(5), 426–433. https://doi.org/10.1016/j.amjmed.2010.12.022
9. Ibrahim, I. M. (2023). Advances in polysaccharide-based oral colon-targeted delivery systems: The journey so far and the road ahead. Cureus, 15(1), e33636. https://doi.org/10.7759/cureus.33636
10. Jain, A., Gupta, Y., & Jain, S. K. (2007). Perspectives of biodegradable natural polysaccharides for site-specific delivery to the colon. Journal of Pharmacy & Pharmaceutical Sciences, 10(1), 86–128.
11. Lee, S. H., Bajracharya, R., Min, J. Y., Han, J. W., Park, B. J., & Han, H. K. (2020). Strategic approaches for colon targeted drug delivery: An overview of recent advancements. Pharmaceutics, 12(1), 68. https://doi.org/10.3390/pharmaceutics12010068
12. Li, Z., Wang, Z., Shen, B., Chen, C., Ding, X., & Song, H. (2020). Effects of aspirin on the gastrointestinal tract: Pros vs. cons. Oncology Letters, 20(3), 2567–2578. https://doi.org/10.3892/ol.2020.11817
13. Philip, A. K., & Philip, B. (2010). Colon targeted drug delivery systems: A review on primary and novel approaches. Oman Medical Journal, 25(2), 79–87. https://doi.org/10.5001/omj.2010.24
14. Rajpurohit, H., Sharma, P., Sharma, S., & Bhandari, A. (2010). Polymers for colon targeted drug delivery. Indian Journal of Pharmaceutical Sciences, 72(6), 689–696. https://doi.org/10.4103/0250-474X.84576
15. Ravi, V., Pramod Kumar, T. M., & Siddaramaiah. (2008). Novel colon targeted drug delivery system using natural polymers. Indian Journal of Pharmaceutical Sciences, 70(1), 111–113. https://doi.org/10.4103/0250-474X.40346
16. Sarangi, M. K., Rao, M. E. B., & Parcha, V. (2021). Smart polymers for colon targeted drug delivery systems: A review. International Journal of Polymeric Materials and Polymeric Biomaterials, 70(16), 1130–1166. https://doi.org/10.1080/00914037.2020.1785455
17. Sinha, V. R., & Kumria, R. (2001). Polysaccharides in colon-specific drug delivery. International Journal of Pharmaceutics, 224(1–2), 19–38. https://doi.org/10.1016/S0378-5173(01)00720-7
18. Tai, F. W. D., & McAlindon, M. E. (2021). Non-steroidal anti-inflammatory drugs and the gastrointestinal tract. Clinical Medicine, 21(2), 131–134. https://doi.org/10.7861/clinmed.2021-0039
19. Van den Mooter, G. (2006). Colon drug delivery. Expert Opinion on Drug Delivery, 3(1), 111–125. https://doi.org/10.1517/17425247.3.1.111
20. Vane, J. R., & Botting, R. M. (2003). The mechanism of action of aspirin. Thrombosis Research, 110(5–6), 255–258. https://doi.org/10.1016/S0049-3848(03)00379-7
21. Yang, L., Chu, J. S., & Fix, J. A. (2002). Colon-specific drug delivery: New approaches and in vitro/in vivo evaluation. International Journal of Pharmaceutics, 235(1–2), 1–15. https://doi.org/10.1016/S0378-5173(02)00004-2.