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Drug Delivery Letters

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ISSN (Print): 2210-3031
ISSN (Online): 2210-304X

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Research Article

Development of Platform Technology for Gastro-resistant Soft Gel Capsules by Using Cross-linking Technique

Author(s): Raja Sekhar*, Md. Shoaib Alam*, Iftikhar Ahsan, Senthil Raja, Thusleem Mohamed and Sheikh Shafiq-un Nabi

Volume 11, Issue 4, 2021

Published on: 27 September, 2021

Page: [325 - 334] Pages: 10

DOI: 10.2174/2210303111666210927112941

Price: $65

Abstract

Introduction: Conventional enteric coating is very challenging in soft gel capsules because of their shell nature (smooth surfaces and elasticity). Soft gelatin capsules are highly sensitive to temperature, humidity and they can lose their tensile strength during the conventional coating process.

Materials and Methods: Enteric soft gel capsules were prepared by the addition of enteric polymer in the gelatin shell composition by inducing the cross-linking of gelatin through chemical treatment.

Results: This dual approach makes the soft gelatin capsules resist the drug release in the stomach and reliably release their contents in the intestine within a predetermined time without affecting the physical properties of soft gel capsules.

Conclusion: Enteric effects of soft gel capsules are brought by a specialized synergetic technique, which is unique for the molecules, requiring intestinal drug release.

Keywords: Soft gel capsule, enteric polymer, cross-linking, chemical treatment, rate of disintegration, alkaline media, formaldehyde content, the morphology of gelatin polymer matrix.

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[1]
Benameur, H. Enteric capsule drug delivery technology—Achieving protection without coating. Drug Des. Deliv., 2015, 15, 34-37.
[2]
Felton, L.A.; Haase, M.M.; Shah, N.H.; Zhang, G.; Infeld, M.H.; Malick, A.W.; McGinity, J.W. Physical and enteric properties of soft gelatin capsules coated with Eudragit® L 30 D-55. Int. J. Pharm., 1995, 113(1), 17-24.
[http://dx.doi.org/10.1016/0378-5173(94)00169-6]
[3]
Gershanik, T.; Benita, S. Self-dispersing lipid formulations for improving oral absorption of lipophilic drugs. Eur. J. Pharm. Biopharm., 2000, 50(1), 179-188.
[http://dx.doi.org/10.1016/S0939-6411(00)00089-8] [PMID: 10840200]
[4]
Gutiérrez-Rocca, J.; McGinity, J.W. Influence of water soluble and insoluble plasticizers on the physical and mechanical properties of acrylic resin copolymers. Int. J. Pharm., 1994, 103(3), 293-301.
[http://dx.doi.org/10.1016/0378-5173(94)90180-5]
[5]
Sydow, G.; Sennhauser, M.; Schluetermann, B.; Prasch, A.; Nehring, R. Gastro-resistant soft shell capsule and process for its manufacture. United States patent application US 14/900,002, 2016.
[6]
Digenis, G.A.; Gold, T.B.; Shah, V.P. Cross-linking of gelatin capsules and its relevance to their in vitro-in vivo performance. J. Pharm. Sci., 1994, 83(7), 915-921.
[http://dx.doi.org/10.1002/jps.2600830702] [PMID: 7965669]
[7]
Jegorov, A.; Szrajber, R. Reduction of cross-linking gelatin in gelatin capsules. United States patent US 8,895,059, 2014.
[8]
Maciejewski, B.; Ström, A.; Larsson, A.; Sznitowska, M. Soft gelatin films modified with cellulose acetate phthalate pseudolatex dispersion-structure and permeability. Polymers (Basel), 2018, 10(9), 981.
[http://dx.doi.org/10.3390/polym10090981] [PMID: 30960906]
[9]
Yoshizato, K.; Yoshikawa, E. Development of bilayered gelatin substrate for bioskin: a new structural framework of the skin composed of porous dermal matrix and thin basement membrane. Mater. Sci. Eng. C, 1994, 1(2), 95-105.
[http://dx.doi.org/10.1016/0928-4931(94)90061-2]
[10]
Nagura, M.; Yokota, H.; Ikeura, M.; Gotoh, Y.; Ohkoshi, Y. Structures and physical properties of cross-linked gelatin fibers. Polym. J., 2002, 34(10), 761-766.
[http://dx.doi.org/10.1295/polymj.34.761]
[11]
Guyot, M.; Fawaz, F.; Maury, M. In vitro release of theophylline from cross-linked gelatin capsules. Int. J. Pharm., 1996, 144(2), 209-216.
[http://dx.doi.org/10.1016/S0378-5173(96)04757-6]
[12]
Ofner, C.M., III; Zhang, Y.E.; Jobeck, V.C.; Bowman, B.J. Crosslinking studies in gelatin capsules treated with formaldehyde and in capsules exposed to elevated temperature and humidity. J. Pharm. Sci., 2001, 90(1), 79-88.
[http://dx.doi.org/10.1002/1520-6017(200101)90:1<79::AID-JPS9>3.0.CO;2-L] [PMID: 11064381]
[13]
Hassan, E.M.; Fatmi, A.A.; Chidambaram, N. Enteric composition for the manufacture of soft capsule wall. United States patent US 8,685,445, 2014.
[14]
Maciejewski, B.; Sznitowska, M. Gelatin films modified with acidic and polyelectrolyte polymers—material selection for soft gastroresistant capsules. Polymers (Basel), 2019, 11(2), 338.
[http://dx.doi.org/10.3390/polym11020338] [PMID: 30960322]
[15]
Leiberich, R.; Gabler, W. Gastric juice resistant gelatin capsules and a process for the production thereof. United States patent US 3,959,540, 1976.
[16]
Aulton’s Pharmaceutics E-Book: The Design and Manufacture of Medicines; Aulton, M.E.; Taylor, K.M., Eds.; Elsevier Health Sciences, 2017..
[17]
Deepak, G.; Kamal, K.; Ajay, B.; Mahesh, K.K. Soft gelatin capsules: development, applications and recent patents. IRJIPS, 2014, 2(3), 163-173.
[18]
Augsburger, LL Hard and soft gelatin capsules. Drugs and the pharmaceutical sciences, 1990, 40, 441-90.
[19]
Schwier, J.R.; Cooke, G.G.; Hartauer, K.J.; Yu, L. A reactive aldehyde capable of insolubilizing gelatin capsules. Pharm. Technol., 1993, 17(5), 78.
[20]
Taylor, S.K.; Davidson, F.; Ovenall, D.W. Carbon-13 nuclear magnetic resonance studies on gelatin crosslinking by formaldehyde. Photogr. Sci. Engng, 1978, 22(3), 134-138.
[21]
Gold, T.B.; Smith, S.L.; Digenis, G.A. Studies on the influence of pH and pancreatin on 13C-formaldehyde-induced gelatin cross-links using nuclear magnetic resonance. Pharm. Dev. Technol., 1996, 1(1), 21-26.
[http://dx.doi.org/10.3109/10837459609031414] [PMID: 9552327]
[22]
Gold, T.B.; Buice, R.G., Jr; Lodder, R.A.; Digenis, G.A. Determination of extent of formaldehyde-induced crosslinking in hard gelatin capsules by near-infrared spectrophotometry. Pharm. Res., 1997, 14(8), 1046-1050.
[http://dx.doi.org/10.1023/A:1012105412735] [PMID: 9279887]
[23]
Gold, T.B.; Buice, R.G., Jr; Lodder, R.A.; Digenis, G.A. Detection of formaldehyde-induced crosslinking in soft elastic gelatin capsules using near-infrared spectrophotometry. Pharm. Dev. Technol., 1998, 3(2), 209-214.
[http://dx.doi.org/10.3109/10837459809028497] [PMID: 9653758]
[24]
Kamiya, S.; Nagae, K.; Hayashi, K.; Suzuki, N.; Hayakawa, E.; Kato, K.; Sonobe, T.; Nakashima, K. Development of a new evaluation method for gelatin film sheets. Int. J. Pharm., 2014, 461(1-2), 30-33.
[http://dx.doi.org/10.1016/j.ijpharm.2013.11.012] [PMID: 24262989]
[25]
Lorén, N.; Langton, M.; Hermansson, A.M. Confocal laser scanning microscopy and image analysis of kinetically trapped phase-separated gelatin/maltodextrin gels. Food Hydrocoll., 1999, 13(2), 185-198.
[http://dx.doi.org/10.1016/S0268-005X(98)00083-6]
[26]
Clair, M.S.; Purdie, J.; Hu, Y.; McGeough, P. The Effect of Cross-Linking on theIn VitroDisintegration of Hard Gelatin Capsules. J. Pharm. Pharmacol., 2010, 62(10), 1235-1236.
[27]
Marchais, H.; Cayzeele, G.; Legendre, J.Y.; Skiba, M.; Arnaud, P. Cross-linking of hard gelatin carbamazepine capsules: effect of dissolution conditions on in vitro drug release. Eur. J. Pharm. Sci., 2003, 19(2-3), 129-132.
[http://dx.doi.org/10.1016/S0928-0987(03)00070-8] [PMID: 12791415]
[28]
Gallery, J; Han, JH; Abraham, C Pepsin and pancreatin performance in the dissolution of crosslinked gelatin capsules from pH 1 to 8. Pharm. Forum, 2004, 30(3), 1084-1089.
[29]
Chiwele, I.; Jones, B.E.; Podczeck, F. The shell dissolution of various empty hard capsules. Chem. Pharm. Bull. (Tokyo), 2000, 48(7), 951-956.
[http://dx.doi.org/10.1248/cpb.48.951] [PMID: 10923822]
[30]
Aboul-Einien, M.H. Formulation and evaluation of felodipine in softgels with a solubilized core. Asian J Pharm Sci., 2009, 4(3), 144-160.
[31]
N Allam, A.; A Komeil, I.; Abdallah, O. Etodolac Softgels: Feasibility Assessment and Considerations for Lipid-Based Formulations of a highly hydrophobic drug. Zagazig J. Pharm. Sci., 2017, 26(1), 1-2.
[http://dx.doi.org/10.21608/zjps.2017.38120]
[32]
Hassan, E.M.; Fatmi, A.A.; Chidambaram, N. Enteric soft capsules. United States patent US 9,433,585, 2016.
[33]
Jain, D; Singh, S. Soft gelatin capsules: A review. Int. J. Pharm. Res., 2012, 2012(4), 07-16.
[34]
Humera, A; Jonathan, D; Jing, L. Enteric softgel capsules. Int. Appl. WO 2019/178481 A1, 2019.
[35]
Maciejewski, B.; Arumughan, V.; Larsson, A.; Sznitowska, M. Prototype gastro-resistant soft gelatin films and capsules-imaging and performance in vitro. Materials (Basel), 2020, 13(7), 1771.
[http://dx.doi.org/10.3390/ma13071771] [PMID: 32283855]
[36]
Tengroth, C.; Gasslander, U.; Andersson, F.O.; Jacobsson, S.P. Cross-linking of gelatin capsules with formaldehyde and other aldehydes: an FTIR spectroscopy study. Pharm. Dev. Technol., 2005, 10(3), 405-412.
[http://dx.doi.org/10.1081/PDT-65693] [PMID: 16176021]
[37]
Duconseille, A.; Astruc, T.; Quintana, N.; Meersman, F.; Sante-Lhoutellier, V. Gelatin structure and composition linked to hard capsule dissolution: A review. Food Hydrocoll., 2015, 43, 360-376.
[http://dx.doi.org/10.1016/j.foodhyd.2014.06.006]
[38]
Mhatre, R.M.; Malinowski, H.; Nguyen, H.; Meyer, M.C.; Straughn, A.B.; Lesko, L.; Williams, R.L. The effects of cross-linking in gelatin capsules on the bioequivalence of acetaminophen. Pharm. Res., 1997, 14(11), 3251.
[39]
Hom, F.S.; Veresh, S.A.; Miskel, J.J. Soft gelatin capsules. I. Factors affecting capsule shell dissolution rate. J. Pharm. Sci., 1973, 62(6), 1001-1006.
[http://dx.doi.org/10.1002/jps.2600620633] [PMID: 4576423]
[40]
Lu, X.; Shah, P. Dissolution of gelatin capsules: Evidence and confirmation of cross-linking. Dissolut. Technol., 2017, 24(3), 6-21.
[http://dx.doi.org/10.14227/DT240317P6]
[41]
Ratna, V; Devineni, J Formulation and evaluation of soft gelatin capsules of nelfinavir mesylate. Eur. J. Biomed. Pharm. Sci., 2016, 3(2), 398-407.
[42]
Prasad, V.D. Formulation and modifying drug release from Hard and Soft Gelatin Capsules for Oral drug delivery. Int. J. Res. Develop. Pharmacy Life Sci., 2017, 6(4), 2663-2677.
[http://dx.doi.org/10.21276/IJRDPL.2278-0238.2017.6(4).2663-2677]
[43]
Davis, P.; Tabor, B.E. Kinetic study of the crosslinking of gelatin by formaldehyde and glyoxal. J. Polym. Sci. A, 1963, 1(2), 799-815.
[http://dx.doi.org/10.1002/pol.1963.100010217]

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