Design, development, formulation and evaluation of hard gelatin aspirin capsule

*Corresponding author: ABARNA P. Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0. Design, development, formulation and evaluation of hard gelatin aspirin capsule ABARNA P *, MITHUN BALA D, SARAL S, SIMMA VISHNU S, SUJITHRA S, RANJITH KUMAR T, SUGUMAR PANDI V and NITHYA K Department of pharmacy, Shri Indra Ganesan Institute of Medical Science, Manikandam, Tiruchirappalli, Tamil Nadu, India. World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 319-325 Publication history: Received on 29 January 2025; revised on 07 March 2025; accepted on 10 March 2025 Article DOI: https://doi.org/10.30574/wjbphs.2025.21.3.0252 Abstract Immediate-release Aspirin capsules are widely used for the treatment of pain, fever, and inflammation, and for the prevention of cardiovascular events. This study focuses on the formulation, development, and evaluation of immediaterelease Aspirin capsules. The primary aim is to design a formulation that ensures rapid disintegration and dissolution, providing quick therapeutic effects. The capsules are prepared using a blend of active pharmaceutical ingredients (Aspirin) and excipients, including starch, lactose, and talc, utilizing a hand-filling method. The stability, dissolution, disintegration, and uniformity of drug content are assessed as per pharmacopeial standards, ensuring that the final product meets the required specifications for efficacy and quality. Stability studies conducted under ICH guidelines confirm that the capsules maintain their potency and integrity over time when stored under recommended conditions. The results of this study contribute to the development of a reliable, immediate-release Aspirin dosage form that provides rapid pain relief, fever reduction, and other therapeutic benefits. Keywords: Aspirin; Hard Gelatin Capsule; Immediate Release; Disintegration; Dissolution 1. Introduction Aspirin is used to reduce fever and relieve mild to moderate pain from conditions such as muscle aches, toothaches, common cold, and headaches. It may also be used to reduce pain and swelling in conditions such as Aspirin, also known as acetylsalicylic acid, is a nonsteroidal anti-inflammatory drug used to reduce pain, fever, and/or inflammation, and as an antithrombotic arthritis.2 Aspirin is classified as a non-selective cyclooxygenase (COX) inhibitor 5,6 and is available in many doses and forms, including chewable tablets, suppositories, extended-release formulations, and others. Acetylsalicylic acid (ASA) or aspirin is one of the most researched medicines in the world and its history can be traced back 3500 years. It belongs to a group of drugs called salicylates which were first used in medicinal purposes in the form of willow bark that contained Salicin. It was used for treating inflammatory joint pains and other inflammatory conditions.7 1.1. Mechanism of action of asprin The mechanism of action of ASA was not known for many years but it was later determined to be a cyclooxygenase (COX) inhibitor (Vane & Botting, 2003). The COX enzyme is required to convert arachidonic acid to prostaglandins. COX isoforms are responsible for different mechanisms in the body and therefore ASA has more than one mechanism of action. COX-1 is a housekeeping enzyme and has a role in platelet aggregation, renal water balance and gastric cytoprotecting. COX-2 has a big role in inflammation and is the main target for non-steroid anti inflammation drugs World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 319-325 320 (Morita, 2002). By irreversible inhibiting COX-1 it blocks the formation of thromboxane which leads to antithrombotic affect and has effect on platelet aggregation (Micromedex, 2021). The inhibition of COX-2 leads to an antiinflammation effect, reduces fever and relieves pain (Vane & Botting, 2003). Different doses of ASA are taken based on what effect of the drug is desired. Lower doses are rather taken for antithrombotic affects than reduction of fever or pain, such as headaches or a migraine. 1.2. Medical uses of aspirin ASA is widely used and has many different indications, both FDA and non-FDA. FDA uses include many kinds of cardiovascular disorders such as angina and myocardial infraction. It is also used for fever, headache, migraine, general pain, and rheumatoid arthritis among other indications. ASA has many non-FDA uses including uses for Kawasaki disease, pregnancy induced hypertension and thromboembolic disorders to name a few. Further, taking low doses of ASA daily can reduce the risk of mortality in women, where it especially reduces the risk of death from cardiovascular disease. 1.3. Indications of the aspirin • Analgesic (Headache, backache, myalgia, joint pain, tooth care) • Antipyretics • Anti-inflammatory • Acute Rheumatic Fever • Rheumatoid Arthritis • Osteo Arthritis • Post myocardial infraction & Post Stroke Patient • Coronary Bypass • Transluminal Angio plasty 1.4. Contra indications of the aspirin • Gastric and duodenal ulcer • Hepatic and renal diseases • Bleeding diathesis • Haemophilia • Third trimester of pregnancy • In Children below 12 years of age. For three reasons aspirin (acetyl salicylic acid or acetyl salicylate) is an immensely important drug. First it is important because millions of people throughout the world can take it. Without heavy expense or having to consult a physician, with no risk of addiction and little of serious toxicity. To comeback several of the minor ills that flesh is heir to. Second, acetyl salicylate is important because, as a result these properties, it becomes for long the most widely uses medicinal drug in the world. As such, it established the fortunes not only for the Rhineland Firme of Bayer that introduce it to the world, but also of several others combines, which, for reasons of war, where able to take over part of is immense market. Third, Aspirin has proud of great important to medical science, because an experimental analysis of its molecular mechanism of action has played a vital role in the discovery of a for reaching system of bodily defences, based on the product of enzyme acting on arachidonic and related unsaturated fatty acid and their metabolites .we may call this the arachidonate and closely related system of lipid local hormones that Sune Bergstrom Bengt Samuelsson and john vane were awarded the 1982 Nobel prize for physiology and medicine. World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 319-325 321 Figure 1 Structure Of ASPIRIN Table 1 Physiochemical Property of Hard Gelatin Aspirin capsule Formula C9H8O4 Molar mass 180.159 g·mol−1 Density 1.40 g/cm3 Melting point 135 °C (275 °F) Boiling point 140 °C (284 °F) (decomposes) Solubility in water 3 g/L Other names 2-acetoxybenzoic acid 2-(acetyloxy)benzoic acid Routes of administration Oral, rectal Drug Class Non-Steroidal anti-inflammatory drug (NSAID) Bio Availability 80-100% Metabolism / Excretion Liver / Urine, Sweat, Saliva, feces 2. Methodology 2.1. Formulation The formulation of the immediate-release Aspirin capsule includes active pharmaceutical ingredients like Aspirin, along with excipients such as starch, lactose, and talc. The formula for preparing a single 100 mg immediate-release Aspirin capsule per batch, utilizing the hand-filling method, is as follows: Table 2 Ingredients for preparing a single 100 mg immediate-release Aspirin capsule. S. No Ingredients F1 F2 F3 F4 F5 1 Aspirin 100 mg 100 mg 100 mg 100 mg 100 mg 2 Starch 50 mg 40 mg 30 mg 55 mg 40 mg 3 Lactose 80 mg 90 mg 100 mg 75 mg 85 mg 4 Talc 20 mg 20 mg 20 mg 20 mg 25 mg Total Weight 250 mg 250 mg 250 mg 250 mg 250 mg World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 319-325 322 3. Result and discussion 3.1. Pre-evaluation study 3.1.1. Angle of repose It is the maximum angle at which a pile of powder or granules remains stable without any material sliding off. It indicates the flowability of the powder. θ = tan^-1(h/r) Where, - θ = Angle of repose - h = Height of the powder pile - r = Radius of the base of the pile Table 3 Flow Property of Hard Gelatin Aspirin Capsule Glidant Angle of Repose F1 F2 F3 F4 F5 Without Glidant 44o 21’± 0.42 39o 56’± 0.56 29o 14’± 0.68 29o 11’± 0.72 35o 36’± 0.85 With Glidant 35o 16’± 0.26 28o 06’± 1.35 25o 06’± 1.49 24o 17’± 1.62 26o 46’± 0.92 3.1.2. Bulk density Bulk density is the mass of powder per unit volume, including void spaces between particles. It reflects the packing of the powder. ρ_b = M/V_b Where, - ρ_b = Bulk density (g/cm³) - M = Mass of powder (g) - V_b = Bulk volume (cm³) (volume of powder including void spaces) 3.1.3. Tapped density Tapped density is the density of the powder after being compacted by tapping or vibration, allowing the particles to settle more tightly. ρ_t = M/V_t Where, - ρ_t = Tapped density (g/cm³) - M = Mass of powder (g) - V_t = Tapped volume (cm³) (volume after tapping) 3.1.4. Carr's index (compressibility index): Carr's Index is a measure of the compressibility of a powder, which helps to assess the flowability and how much the powder can be compacted. ρ_t - ρ_b/ρ_t× 100 Where, - ρ_t = Tapped density - ρ_b = Bulk density World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 319-325 323 3.1.5. Hausner ratio The Hausner Ratio is a ratio of tapped density to bulk density. It provides an estimate of the powder's flow properties. ρ_t/ρ_b Where, - ρ_t = Tapped density - ρ_b = Bulk density 3.2. Disintegration test • Equipment: Use a disintegration apparatus fitted with a basket-rack assembly containing six tubes, each with a mesh screen at the bottom. • Medium: Place the capsules in a 0.1 N HCl solution (simulating gastric fluid) maintained at 37 ± 0.5°C. • Duration: Operate the apparatus for 15–30 minutes or as specified in the pharmacopeial guidelines for Aspirin capsules. Table 4 Disintegration Rate of Hard Gelatin Capsule Serial No. of Capsule Disintegration Time (Mins) 1 10 2 10 3 10 4 10 5 10 6 10 3.3. Dissolution test In this test, capsules are placed in a dissolution apparatus (usually a basket or paddle apparatus) containing a liquid medium (e.g., water, buffer solution). The capsules are rotated at a specified speed, and the concentration of the drug in the solution is measured at different time intervals to determine how quickly the active ingredient is released from the capsule. • The capsule releases its drug over time, and the dissolution profile shows how much of the drug is dissolved in the medium. • A rapid release within 5-10 minutes is generally preferred for immediate-release formulations. The Immediate-release capsules should release the active ingredient quickly (within 5-10 minutes) so that the drug starts working fast in the body. Table 5 Dissolution rate of hard gelatin capsule Formulation Code S. No F1 F2 F3 F4 F5 Pure Drug ± SD 10 8.91±1.307 10.69±0.758 14.2±0.634 17.82±0.667 16.1±0.707 14±0.22 20 15.57±0.908 18.36±0.357 21.24±0.627 28.26±0.707 24.03±0.384 22±0.68 30 25.33±1.980 26.6±0.786 30.6±0.818 40.1±1.842 34.6±1.403 41±0.85 40 31.95±0.895 37.8±0.820 38.43±0.485 51.12±0.632 48.6±0.489 53±1.25 50 68.46±1.474 72.1±0.693 75.9±0.456 87.13±0.934 79.6±1.964 62±1.54 60 85.5±0.482 86.1±0.487 88.56±0.432 98.1±0.930 95.94±0.894 71±1.79 World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 319-325 324 Figure 2 Effect of formulation (f1-f5) on absorption rate” 4. Conclusion The results clearly show that the formulations exhibit a rapid release of the active ingredient, which is a characteristic feature of immediate-release formulations. The dissolution data indicates a quick and consistent release of Aspirin within the first 10 to 20 minutes of administration. This rapid release ensures that the drug reaches therapeutic concentrations in the bloodstream promptly, providing quick pain relief for conditions requiring fast action, like fever, headache, or mild to moderate pain. By observing the in-vitro drug release, F4 is best formulation, because it shows [98.1%± 0.930] drug release more than the other formulations. In the F4 formulation, Disintegration agent [starch] is added more and binding agent is added less. The dissolution profiles of F1, F2, F3, F4, F5 show that the release of Aspirin is uniform and consistent, confirming the suitability of these capsules for immediate-release applications. The data suggests that these formulations are effective in achieving rapid therapeutic effects, ensuring that patients get timely relief. This study highlights the importance of formulation design in optimizing the drug release characteristics. The Aspirin 100 mg capsules show promise as an immediate-release dosage form, offering fast and effective action. However, further studies on bioavailability and clinical trials are recommended to confirm these results in real-world applications. Compliance with ethical standards Acknowledgments I convey my acknowledgement to the management of Shri Indra Ganesan Institute of Medical Science College of Pharmacy, Manikandam, Tiruchirappalli, Tamil Nadu, India. Disclosure of conflict of interest The Author declare that there is no conflict of interest to be disclosed. 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[8] http://www.aspirin.com/scripts/pages/en/aspirin_history/index.php [9] http://en.wikipedia.org/wiki/Aspirin [10] http://en.wikipedia.org/wiki/History_of_aspirin [11] http://www.wonderdrug.com/pain/asp_history.htm [12] riend DG. Aspirin: The unique drug. Arch Surg 1974; 108(6): [13] Brandt KD. Medical management of the patient with arthritis. Clin Orthop Relat Res 1974; (101):13-27. [14] Michael J. Parnham, Clive Page, Jacques Bruinvels Elsevier, 23 Oct 2023 - Medical - 500 pages Haemodynamics and Immune Defence: Discoveries in Pharmacology, Second Edition [15] https://doi.org/10.1136/bmj.321.7276.1591 (Published 23 December 2000) Cite this as: BMJ 2000;321:1591 Authors short Biography I’m Abarna P, currently in my final year of Bachelor of Pharmacy (B. Pharm). My academic journey in pharmacy has been enriching, and I’m excited to apply my knowledge in the healthcare field. Outside of studies, I enjoy reading historical books, which have broadened my understanding of different cultures and timelines. I’m passionate about personal growth and believe in continuous learning. As I approach the end of my degree, I’m focused on gaining practical experience and looking forward to contributing to the pharmaceutical industry.