Development of Transdermal and Transbuccal Drug Delivery Systems for Cardioactive Drugs with Special Reference to Anti- Hypertensive Agents

  • S. S. Agrawal
Part of the Progress in Experimental Cardiology book series (PREC, volume 8)


The effectiveness and better patient compliance is driving a steady increase in the use of transdermal patches and buccal films that deliver an array of drugs ranging from hormones to pain relievers and drugs acting on cardiovascular system.

Key words

Transdermal drug delivery systems (TDS) Transmucosal delivery (TMD) Carvedilol Verapamil HC1 (VHC1) Diltiazem HC1 (DTZHC1) Atenolol 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Mishra B, Pandit JK, Bhattacharya SK. 1990. Recent trends in drug delivery systems: Transdermal drug delivery. Indian J Exp Biol 28:1001–1007.PubMedGoogle Scholar
  2. 2.
    Harris D, Robinson JR. 1992. Drug delivery via the mucous membranes of the oral cavity. J Pharm Sci 81:1–10.PubMedCrossRefGoogle Scholar
  3. 3.
    Gandhi FJ3, Robinson JR. 1994. Oral cavity as a site for bioadhesive drug delivery. Adv Drug Del Rev 13:43–74.CrossRefGoogle Scholar
  4. 4.
    Tabak LA, Levine MJ, Mandel ID, Ellison SA. 1982. Role of salivary mucins in the protection of the oral cavity. J Oral Pathol 11:1–17.PubMedCrossRefGoogle Scholar
  5. 5.
    Peppas NA, Buri PA. 1985. Surface interfacial and molecular aspects of polymer bioadhesion on soft tissues. J Controlled Release 2:257–275.CrossRefGoogle Scholar
  6. 6.
    Shojaei AH. 1998. Buccal mucosa as a route for systemic drug delivery: J Pharm Pharmaceut Sci 1:15–30.Google Scholar
  7. 7.
    Rathbone MJ, Tucker IG. 1993. Mechanisms, barriers and pathways of oral mucosal drug permeation. Adv Drug Del Rev 12:41–60.CrossRefGoogle Scholar
  8. 8.
    Ho NFH. 1993. Biophysical kinetic modeling of buccal absorption. Adv Drug Del Rev 12:61–97.CrossRefGoogle Scholar
  9. 9.
    Gary RH. 1987. Drug parameters important for transdermal delivery. In: Transdermal Delivery of Drugs Vol III Ed A F Kydonieus, B Berner 3–22 Florida: CRC Press.Google Scholar
  10. 10.
    Guy RH, Hadgraft J. 1985. Kinetic analysis of transdermal Nitroglycerin Delivery Pharm Res 2:206–209.Google Scholar
  11. 11.
    Guy RH, Hadgraft J. 1985. Pharmacokinetic interpretation of plasma levels of clonidine following transdermal delivery J Pharm Sci 74:1016–1021.Google Scholar
  12. 12.
    Jerath K. 2001. Development and evaluation of transdermal drug delivery system of carvedilol. M. Pharm Thesis, University of Delhi, India.Google Scholar
  13. 13.
    Jain G. 1995. Development of transdermal drug delivery system for vasoactive drugs, Ph.D. Thesis, University of Delhi, India.Google Scholar
  14. 14.
    Munshi N. 1997. In vitro and in vivo evaluation of transdermal therapeutic system of verapamil hydrochloride using terpenes as skin penetration enhancers and its pharmacodynamic study. M. Pharm Thesis, University of Delhi, India.Google Scholar
  15. 15.
    Gupta B. 1999. Development of transdermal therapeutic system of diltiazem hydrochloride using guinea pig dorsal and cadaver skin. M. Pharm Thesis, University of Delhi, India.Google Scholar
  16. 16.
    Misra AN. 1997. Transdermal drug delivery In: Controlled and Novel Drug Delivery. Ed NK Jain, 100–129 New Delhi: CBS Publishers and Distributors.Google Scholar
  17. 17.
    Ch’ng HS, Park H, Kelly P, Robinson JR. 1985. Bioadhesive polymers as platforms for oral controlled drug delivery II: Synthesis and evaluation of some swelling water-insoluble bioadhesive polymers J Pharm Sci 74:399–405.PubMedCrossRefGoogle Scholar
  18. 18.
    Gandhi RE, Robinson JR. 1988. Bioadhesion in drug delivery. Ind J Pharm Sci 50:145–152.Google Scholar
  19. 19.
    Sanzgiri YD, Topp EM, Beneditti L, Stella VJ. 1994. Evaluation of mucoadhesive properties of hyaluronic acid benzylesters. Int J Pharm 107:91–97.CrossRefGoogle Scholar
  20. 20.
    Park K, Robinson JR. 1984. Bioadhesive polymers as platforms for oral controlled drug delivery: Method to study biodhesion. Int J Pharm 19:107–127.CrossRefGoogle Scholar
  21. 21.
    Lehr CM, Bouwstra JA, Schact EH, Junginger HE. 1992. In vitro evaluation of mucoadhesive properties of chitosan and some other natural polymers. Int J Pharm 78:43–48.CrossRefGoogle Scholar
  22. 22.
    Agrawal SS, Agarwal SP, Goel A. 2001. Transdermal conception control system containing Ocimum sanctum oil as penetration enhancer. Indian Patent Appl No 673/Del/2001.Google Scholar
  23. 23.
    Hoogstraate AJ, Verhoef JC, Tuli B, Pypers LAG, Junginger HE, Bodde HE. 1996. In vivo buccal delivery of fluorescent isothiocyanate dextran 4400 with glycodeoxycholate as an absorption enhancer in pigs. J. Pharm Sci 85:457–460.PubMedCrossRefGoogle Scholar
  24. 24.
    Hoogstraate AJ, Senel S. 1996. Effects of Bile salts on transport rates and routes of FTIC labeled compounds across porcine buccal epithelium in vitro. J Controlled Release 40:211–221.CrossRefGoogle Scholar
  25. 25.
    Sensel S, Capan Y, Sargon MF. 1997. Enhancement of transbuccal permeation of morpphine sulphare by sodium glycodeoxycholate in vitro.] Controlled Release 45:153–162.CrossRefGoogle Scholar
  26. 26.
    Aungst BJ. 1988. Comparison of nasal rectal, buccal, sublingual and intramuscular insulin efficacy and the effects of a bile salt absorption promoter. J Pharmacol Exp Ther 244:23–27.PubMedGoogle Scholar
  27. 27.
    Aungst BJ, Rogers NJ. 1988. Site dependance of absorption promoting actions of Laureth-9 Na salicylate Na2EDTA Aprotinin on rectal, nasal and buccal insulin delivery. Pharm Res 5:305–308.CrossRefGoogle Scholar
  28. 28.
    Oates JA, Brown NJ. 2001. Antihypertensive agents and drug therapy of hypertension In: Goodman and Gilman’s The Pharmacological Basis of Therapeutics Ed Joel G Hardman, Lee E Limbird, 871–900 USA: McGraw-Hill Medicine Publishing Division.Google Scholar
  29. 29.
    Keith AD. 1983. Polymer matrix consideration for transdermal devices Drug Dev Ind Pharm 9:605–625.CrossRefGoogle Scholar
  30. 30.
    Ryden L. 1987. Buccal vs sublingual glyceryl trinitrate administration in treatment of angina pectoris. Drugs 33:96–99.PubMedCrossRefGoogle Scholar
  31. 31.
    Abrams J. 1984. Nitrate delivery systems in perspective. Am J Med 76:38–46.PubMedCrossRefGoogle Scholar
  32. 32.
    Bhalla HL, Damle AV,Toddywala RD. 1985. Transdermal films of isosorbide dinitrate. Drug Dev Ind Pharm 14:119–131.CrossRefGoogle Scholar
  33. 33.
    Nozaki Y, Kakumato M, Ohta M, Yakimetsu M. 1993. A new transmucosal therapeutic system: An overview of formulation development and in vitro clinical performance. Drug Dev Ind Pharm 19:1755–1808.CrossRefGoogle Scholar
  34. 34.
    Danjo K, Kitamura Y, Miyagawa Y, Otsuka A. 1994. Release of isosorbide dinitrate from polymer film dosage forms and absorption of this drug through the oral mucosa of rats. Chem Pharm bull 42:2126–2130.PubMedCrossRefGoogle Scholar
  35. 35.
    Zierenberg B. 1983. Experimental and Theoretical studies on the diffusion of drugs in polymer films. Drug Dev Ind Pharm 9:117–137.CrossRefGoogle Scholar
  36. 36.
    Weber MA, Brewer DD, Drayer JI, Lipson JL. 1984. Transdermal continuous antihypertensive therapy. Lancet 1:9–16.PubMedCrossRefGoogle Scholar
  37. 37.
    Verma PR, Iyer SS. 2000. Controlled transdermal delivery of propranolol using HPMC matrices: Design and in vitro and in vivo evaluation. J Pharm Pharmacol 52:151–156.PubMedCrossRefGoogle Scholar
  38. 38.
    Rao PR, Diwan PV. 1997. Permeability studies of cellulose acetate free films for transdermal use: Influence of plasticizers. Pharm Acta Helv 72:47–51.PubMedCrossRefGoogle Scholar
  39. 39.
    Corbo M, Liu JC, Chien YW. 1989. Transdermal controlled delivery of Propranolol from a multil-aminate adhesive device. Pharm Res 6:753–758.PubMedCrossRefGoogle Scholar
  40. 40.
    Al-Hmound H, Efentakis M, Choulis NH. 1991. A controlled release matrix using a mixture of hydrophilic and hydrophobic polymers. Int J Pharm 68:R1–R3.CrossRefGoogle Scholar
  41. 41.
    Le Brun PPH, Fox PLA, De Vries ME, Bodde HE. 1989. In vitro penetration of some p adreno-ceptor blocking drugs through porcine buccal mucosa. Int J Pharm 49:141–145.CrossRefGoogle Scholar
  42. 42.
    Kislal O, Celabi N. 1992, Studies on buccoadhesive tablet formulation of propranol HC1. Proceed of Int Symp on Control Bioact Mat 19:397–398.Google Scholar
  43. 43.
    Chen WG, Hwang GC. 1992. Adhesive and in vitro release characteristics of propranolol biodhesive disc system. Int J Pharm 82:61–66.CrossRefGoogle Scholar
  44. 44.
    Nielsen HM, Rassing MR. 2000. TR146 cells grown on filter as a model of human buccal epithe-lium: IV permeability of water, mannitol, testosterone and ¦Â adrenoceptor antagonists. Int J Pharm 194:155–167.PubMedCrossRefGoogle Scholar
  45. 45.
    Kaul JL, Jain GK, Agrawal SS. 1993. In vitro transdermal delivery of atenolol using mouse and guinea pig. Ind J Expl Biol 31:691–693.Google Scholar
  46. 46.
    Ghosh TK, Adir J, Xiang SL, Onyilofur S. 1995. Transdermal delivery of metoprolol: In vitro skin permeation and bioavailability in hairless rats. J Pharm Sci 84:153–157.Google Scholar
  47. 47.
    Wong CF, Yuen KH, Peh KK. 1999. Formulation and evaluation of controlled release eudragit buccal patches. Int J Pharm 178:11–22.PubMedCrossRefGoogle Scholar
  48. 48.
    Bondi JV, Loper AE, Cohen EM. 1987. Transdermal system for timolol. Eur Pat Appl EP 186071 through CA 106:23288.Google Scholar
  49. 49.
    Dinsheet, Agarwal SP, Ahuja A. 1997. Preparation of Evaluation of Mucoadhesive buccal Tablets of hydralazine hydrochloride. Indian Journal Pharm. Sci 59:135–141.Google Scholar
  50. 50.
    Ruan LP, Zheng JM. 1991. Research on nifedipine patch. Acta Pharm Sinica 26:286–292. Through IPA: 2902107.Google Scholar
  51. 51.
    Save T, Venkitachalam P. 1994. Buccoadhesive tablets of nifedipine standardization of a novel buccoadhesive erodible carrier. Drug Dev Ind Pharm 20:3005–3014.CrossRefGoogle Scholar
  52. 52.
    Remunan LC, Portero A, Vila JJL, Alonso MJ. 1998. Design and evaluation of chitosan/ethylcellulose mucoadhesive bilayered devices for buccal drug delivery. J Controlled Release 55:143–152.CrossRefGoogle Scholar
  53. 53.
    Chien YW, Tojo K. 1987. Transdermal Verapamil delivery Device PCT. Int Appl W O 870042 Chem Abstract 107:64932.Google Scholar
  54. 54.
    Sawicki W. 2001. Penetration of Verapamil Hydrochloride in the presence of sodium glycocholate as penetration enhancer through mucous membrane. Pharmazie 56:74–77.PubMedGoogle Scholar
  55. 55.
    Jain GK, Agrawal SS. 1996. In vitro percutaneous absorption of Verapamil. Ind J Expl Biol 34: 475–477.Google Scholar
  56. 56.
    Verma DD. 1996. Development and Pharmacokinetic evaluation of Transdermal Drug Delivery System of Verapamil HC1. M. Pharm Thesis, University of Delhi, India.Google Scholar
  57. 57.
    Miyazaki S, Nakayama A, Oda M, Takada M, Attwood D. 1994. Chitosan and sodium alginate based bioadhesive tablet for intraoral drug delivery. Biol Pharm bull 17:745–747.PubMedCrossRefGoogle Scholar
  58. 58.
    Ahuja A, Dogra M, Agarwal SP. 1995. Development of buccal tablets of Diltiazem hydrochloride. Indian J. Pharm Sci 57:26–30.Google Scholar
  59. 59.
    Kochhar JK. 2002. Develoment and evaluation of Buccal Drug Delivery system of Carvedilol, M Pharm (Thesis work in progress).Google Scholar
  60. 60.
    Gupta A, Garg S, Khar RK. 1992. Measurement of bioadhesive strength of mucoadhesive buccal tablets: Design of in vitro assembly. Indian Drugs 30:152–155.Google Scholar
  61. 61.
    Gummer CL, Hinz RS, Maibach HI. 1987. The skin penetration cell: A design update. Int J Pharm 40:101–104.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • S. S. Agrawal
    • 1
  1. 1.Dept. of PharmacologyCollege of Pharmacy Pushp ViharIndia

Personalised recommendations