Gelatine capsules are widely used in the pharmaceutical and nutraceutical industries for over a century due to their easy-to-swallow nature and their ability to release pharma active ingredients in a controlled manner. However, due to growing concerns over health, ethical issues, and environmental issues associated with the use of animal-derived products, there has been a significant interest towards developing natural, plant-based, and synthetic alternatives to gelatine. This article briefly explores the various natural polymers that have been studied and developed / being developed as a substitute for gelatine capsules, focusing on their important properties, applications, advantages, and challenges. Gelatine capsules have been a pharmaceutical standard for over a century due to their biocompatibility and controlled drug release properties. However, ethical, health, and environmental concerns regarding animal-derived gelatine have driven research into natural polymer alternatives. This review explores plant-based and microbial polymers such as hydroxypropyl methylcellulose (HPMC), starch, agar, alginate, pullulan, and chitosan as viable substitutes. These alternatives offer biocompatibility, stability, and dissolution properties suitable for pharmaceutical applications, though challenges such as mechanical strength and cost remain. Advancements in formulation technologies will further enhance their feasibility for mainstream adoption in capsule manufacturing.

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1. Villiers M. Oral Conventional Solid Dosage Forms: Powders and Granules, Tablets, Lozenges, and Capsules. In: Ghosh TK, Jasti BR, editors. Theory and Practice of Contemporary Pharmaceutics. New York: CRC Press; 2005. p. 273–326.
2. Lozano M del C, Córdoba D, Córdoba M. Manual de Tecnología Farmacéutica. Barcelona: Elsevier; 2012.
3. Deepak G, Kamal K, Ajay B, Kumar Mahesh K. Soft Gelatine Capsules: development, applications and recent patents. Int Res J Invent Pharm Sci. 2014;2(3):163–73.
4. Gullapalli R. Soft Gelatine Capsules. J Pharm Sci. 2010;99(10):798–809.
5. Puertas-Bartolomé M, Mora-Boza A, García-Fernández L. Emerging Bio-fabrication Techniques: A Review on Natural Polymers for Biomedical Applications. Polymers. 2021;13(1209). doi: 10.3390/polym13081209.
6. Aravamudhan A, Ramos DM, Nada AA, Kumbar SG. Natural and Synthetic Biomedical Polymers. Amsterdam: Elsevier; 2014. Chapter 4—Natural Polymers: Polysaccharides and Their Derivatives for Biomedical Applications; p. 67–89. Available from: https://www.sciencedirect.com/science/article/abs/pii/B9780123969835000041
7. Schultz B, Snow ES, Walker S. Mechanism of D-Alanine Transfer to Teichoic Acids Shows How Bacteria Acylate Cell Envelope Polymers. Nat Microbiol. 2023;8:1318–29. doi: 10.1038/s41564-023-01411-0.
8. Caillol S. Special Issue “Natural Polymers and Biopolymers II”. Molecules. 2020;26(112). doi: 10.3390/molecules26010112.
9. Rajeswari S. Natural Polymers: A Recent Review. World J Pharm Pharm Sci. 2017;6:472–94. doi: 10.20959/wjpps20178-9762.
10. Silva ACQ, Silvestre AJD, Vilela C, Freire CSR. Natural Polymers-Based Materials: A Contribution to a Greener Future. Molecules. 2022;27(94). doi: 10.3390/molecules27010094.
11. Al-Tabakha MM. HPMC capsules: current status and future prospects. J Pharm Sci. 2010;13(3):428–42. doi: 10.18433/j3k881. PMID: 21092714.
12. Vilivalam VD, Illum L, Iqbal K. Starch capsules: an alternative system for oral drug delivery. Pharm Sci Technol Today. 2000;3(2):64–9. doi: 10.1016/S1461-5347(99)00238-2.
13. Karim AA, Bhat R. Gelatine alternatives for the food industry: recent developments, challenges and prospects. Trends Food Sci Technol. 2008;19(12):644–56. doi: 10.1016/j.tifs.2008.08.001.
14. Raus RA, Nawawi WMFW, Nasaruddin RR. Alginate and alginate composites for biomedical applications. Asian J Pharm Sci. 2021;16(3):280–306. doi: 10.1016/j.ajps.2020.10.001.
15. Kalmer RR, Karimi A, Ramezanalizadeh H, Ghanbari M, Samandarian D, Sadjadinia A, et al. Design and preparation of a novel pullulan hard capsule formulation: A promising green candidate and study of crucial capsule features. Heliyon. 2024;10(7):e28969. doi: 10.1016/j.heliyon.2024.e28969. PMID: 38617967; PMCID: PMC11015124.
16. Mehdi-Sefiani H, Granados-Carrera CM, Romero A, Chicardi E, Domínguez-Robles J, Perez-Puyana VM. Chitosan–Type-A-Gelatine Hydrogels Used as Potential Platforms in Tissue Engineering for Drug Delivery. Gels. 2024;10(419). doi: 10.3390/gels10070419.

Gelatine capsules are widely used in the pharmaceutical and nutraceutical industries for over a century due to their easy-to-swallow nature and their ability to release pharma active ingredients in a controlled manner. However, due to growing concerns over health, ethical issues, and environmental issues associated with the use of animal-derived products, there has been a significant interest towards developing natural, plant-based, and synthetic alternatives to gelatine. This article briefly explores the various natural polymers that have been studied and developed / being developed as a substitute for gelatine capsules, focusing on their important properties, applications, advantages, and challenges. Gelatine capsules have been a pharmaceutical standard for over a century due to their biocompatibility and controlled drug release properties. However, ethical, health, and environmental concerns regarding animal-derived gelatine have driven research into natural polymer alternatives. This review explores plant-based and microbial polymers such as hydroxypropyl methylcellulose (HPMC), starch, agar, alginate, pullulan, and chitosan as viable substitutes. These alternatives offer biocompatibility, stability, and dissolution properties suitable for pharmaceutical applications, though challenges such as mechanical strength and cost remain. Advancements in formulation technologies will further enhance their feasibility for mainstream adoption in capsule manufacturing.

🔒 This is a subscription article

Full text is available to subscribers and institutional members. Please choose an option below to access it.

1. Villiers M. Oral Conventional Solid Dosage Forms: Powders and Granules, Tablets, Lozenges, and Capsules. In: Ghosh TK, Jasti BR, editors. Theory and Practice of Contemporary Pharmaceutics. New York: CRC Press; 2005. p. 273–326.
2. Lozano M del C, Córdoba D, Córdoba M. Manual de Tecnología Farmacéutica. Barcelona: Elsevier; 2012.
3. Deepak G, Kamal K, Ajay B, Kumar Mahesh K. Soft Gelatine Capsules: development, applications and recent patents. Int Res J Invent Pharm Sci. 2014;2(3):163–73.
4. Gullapalli R. Soft Gelatine Capsules. J Pharm Sci. 2010;99(10):798–809.
5. Puertas-Bartolomé M, Mora-Boza A, García-Fernández L. Emerging Bio-fabrication Techniques: A Review on Natural Polymers for Biomedical Applications. Polymers. 2021;13(1209). doi: 10.3390/polym13081209.
6. Aravamudhan A, Ramos DM, Nada AA, Kumbar SG. Natural and Synthetic Biomedical Polymers. Amsterdam: Elsevier; 2014. Chapter 4—Natural Polymers: Polysaccharides and Their Derivatives for Biomedical Applications; p. 67–89. Available from: https://www.sciencedirect.com/science/article/abs/pii/B9780123969835000041
7. Schultz B, Snow ES, Walker S. Mechanism of D-Alanine Transfer to Teichoic Acids Shows How Bacteria Acylate Cell Envelope Polymers. Nat Microbiol. 2023;8:1318–29. doi: 10.1038/s41564-023-01411-0.
8. Caillol S. Special Issue “Natural Polymers and Biopolymers II”. Molecules. 2020;26(112). doi: 10.3390/molecules26010112.
9. Rajeswari S. Natural Polymers: A Recent Review. World J Pharm Pharm Sci. 2017;6:472–94. doi: 10.20959/wjpps20178-9762.
10. Silva ACQ, Silvestre AJD, Vilela C, Freire CSR. Natural Polymers-Based Materials: A Contribution to a Greener Future. Molecules. 2022;27(94). doi: 10.3390/molecules27010094.
11. Al-Tabakha MM. HPMC capsules: current status and future prospects. J Pharm Sci. 2010;13(3):428–42. doi: 10.18433/j3k881. PMID: 21092714.
12. Vilivalam VD, Illum L, Iqbal K. Starch capsules: an alternative system for oral drug delivery. Pharm Sci Technol Today. 2000;3(2):64–9. doi: 10.1016/S1461-5347(99)00238-2.
13. Karim AA, Bhat R. Gelatine alternatives for the food industry: recent developments, challenges and prospects. Trends Food Sci Technol. 2008;19(12):644–56. doi: 10.1016/j.tifs.2008.08.001.
14. Raus RA, Nawawi WMFW, Nasaruddin RR. Alginate and alginate composites for biomedical applications. Asian J Pharm Sci. 2021;16(3):280–306. doi: 10.1016/j.ajps.2020.10.001.
15. Kalmer RR, Karimi A, Ramezanalizadeh H, Ghanbari M, Samandarian D, Sadjadinia A, et al. Design and preparation of a novel pullulan hard capsule formulation: A promising green candidate and study of crucial capsule features. Heliyon. 2024;10(7):e28969. doi: 10.1016/j.heliyon.2024.e28969. PMID: 38617967; PMCID: PMC11015124.
16. Mehdi-Sefiani H, Granados-Carrera CM, Romero A, Chicardi E, Domínguez-Robles J, Perez-Puyana VM. Chitosan–Type-A-Gelatine Hydrogels Used as Potential Platforms in Tissue Engineering for Drug Delivery. Gels. 2024;10(419). doi: 10.3390/gels10070419.