Skip to main content

Controlled Release Intravaginal Veterinary Drug Delivery

  • Chapter
  • First Online:
Long Acting Animal Health Drug Products

Abstract

This chapter describes the current scope of intravaginal drug delivery in livestock. Pre-formulation, manufacturing, pharmacokinetic, and technological aspects of product design are considered. Historical developments are briefly reviewed, while product developments that have occurred over the past decade are described in detail. The chapter concludes with a look into the future and suggests some future needs that, if filled, could extend the use of vagina of livestock as a route of administration and make available a wider range and scope of products for use in the industry.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Rathbone MJ, Macmillan KL, Bunt CR, Burggraaf S, Burke C (1997) Conceptual and commercially available intravaginal veterinary drug delivery systems. Adv Drug Deliv Rev 28:363–392

    Article  PubMed  Google Scholar 

  2. Rathbone MJ, Macmillan KL, Inskeep K, Day M, Burggraaf S, Bunt CR (1997) Fertility regulation in cattle (invited review). J Control Release 54:117–148

    Article  Google Scholar 

  3. Rathbone MJ, Macmillan KL, Jöchle W, Boland M, Inskeep K (1998) Controlled release products for the control of the estrous cycle in cattle, sheep, goats, deer, pigs and horses (invited review). Crit RevTher Drug Carrier Syst 15:285–380

    CAS  Google Scholar 

  4. Rathbone MJ, Kinder JE, Fike K, Kojima F, Clopton D, Ogle CR, Bunt CR (2001) Recent advances in bovine reproductive endocrinology and physiology and their impact on drug delivery system design for the control of the estrous cycle in cattle. Adv Drug Deliv Rev 50:277–320

    Article  CAS  PubMed  Google Scholar 

  5. Rathbone MJ, Witchey-Lakshmanan L, Ciftci KK, Rathbone MJ, Witchey-Lakshmanan L, Ciftci KK (1999) Veterinary applications of controlled release drug delivery. In: Mathiowitz E (ed) Encyclopedia of controlled drug delivery. Wiley, New York, pp 1007–1037

    Google Scholar 

  6. Robinson JR, Rathbone MJ (1999) Mucosal drug delivery—rectal, uterine and vaginal. In: Mathiowitz E (ed) Encyclopaedia of controlled drug delivery. Wiley, New York

    Google Scholar 

  7. Rathbone MJ, Foster TP (2009) Veterinary pharmaceutical dosage forms. In: Florence AT, Siepmann J (eds) Modern pharmaceutics. Applications and advances, vol 2, Drugs and the pharmaceutical sciences series. Informa Healthcare, New York

    Google Scholar 

  8. Rathbone MJ, Burke CR, Ogle CR, Bunt CR, Burggraaf S, Macmillan KL (2000) Design and development of controlled release intravaginal veterinary drug delivery systems. In: Rathbone MJ, Gurny R (eds) Controlled release veterinary drug delivery: biological and pharmaceutical considerations, Chap. 6. Elsevier Science B.V, Amsterdam, The Netherlands, pp 173–200

    Chapter  Google Scholar 

  9. Rathbone MJ, Burns PJ, Ogle CR, Burggraaf S, Bunt CR (2000) Controlled release drug delivery systems for estrous control of domesticated livestock. In: Rathbone MJ, Gurny R (eds) Controlled release veterinary drug delivery: biological and pharmaceutical considerations, Chap. 7. Elsevier Science B.V, Amsterdam, The Netherlands, pp 201–228

    Chapter  Google Scholar 

  10. Rathbone MJ, Brayden D (2009) Controlled release drug delivery in farmed animals: commercial challenges and academic opportunities. Curr Drug Deliv 6:383–390

    Article  CAS  PubMed  Google Scholar 

  11. Rathbone MJ, Macmillan KL (2004) Applications of controlled release science and technology: progesterone. Controlled Release Newsl 21:8–9

    Google Scholar 

  12. Brayden DJ, Oudot EM, Baird AW (2009) Drug delivery systems in domestic animals. In: Cunningham F, Elliott J, Lees P (eds) Handbook of experimental pharmacology: comparative and veterinary pharmacology. Springer, Berlin

    Google Scholar 

  13. King BF (1985) Ruthenium red staining of vaginal epithelial cells and adherent bacteria. Anat Rec 212:41–46

    Article  CAS  PubMed  Google Scholar 

  14. Miroud K, Noakess DE (1990) Exfoliative vaginal cytology during the oestrous cycle of the cow, after ovariectomy, and after exogenous progesterone and oestradiol-17 beta. Br Vet J 146:387–397

    Article  CAS  PubMed  Google Scholar 

  15. Sisson S, Grossman JD (1975) The anatomy of the domestic animals, 5th edn. W. B. Saunders, Philadelphia, 1975

    Google Scholar 

  16. Edwards DF, Levin RJ (1974) An electrical method of detecting the optimum time to inseminate cattle, sheep and pigs. Vet Rec 95:416–420

    Article  CAS  PubMed  Google Scholar 

  17. Oxenreider SL, McClure RC, Day BN (1965) Arteries and veins of the internal genitalia of female swine. J Reprod Fertil 9:19–27

    Article  CAS  PubMed  Google Scholar 

  18. Maximow AA, Bloom W (1942) A textbook of histology, Chap. 25. W. B. Saunders, Philadelphia

    Google Scholar 

  19. Cole HH (1930) A study of the mucosa of the genital tract of the cow, with special reference to cyclic changes. Am J Anat 46:261–302

    Article  Google Scholar 

  20. Abrams RM, Thatcher WW, Chenault JR, Wilcox CJ (1975) Bovine vaginal circulation: changes during estrous cycle. J Dairy Sci 58:1528–1530

    Article  CAS  PubMed  Google Scholar 

  21. Hansel W, Asdell SA (1951) The effects of estrogen and progesterone on the arterial system of the uterus of the cow. J Dairy Sci 34:37

    Article  Google Scholar 

  22. Restall BJ (1966) Histological observations on the reproductive tract of the ewe. Aust J Biol Sci 19:673–686

    Article  CAS  PubMed  Google Scholar 

  23. Cole HH, Miller RF (1935) Changes in the reproductive organs of the ewe with some data bearing on their control. Am J Anat 57:39–97

    Article  Google Scholar 

  24. Blazquez NB, Batten EH, Long SE, Perry GC (1987) Histology and histochemistry of the bovine reproductive tract caudal to the cervix Part I. The vestibule and associated glands. Br Vet J 143:328–337

    Article  CAS  PubMed  Google Scholar 

  25. Maximow AA, Bloom W (1942) A textbook of histology, Chap. 11. W. B. Saunders, Philadelphia

    Google Scholar 

  26. Miroud K, Noakes DE (1991) Histological changes in the vaginal mucosa of the cow during the oestrous cycle, after ovariectomy and following exogenous oestradiol benzoate and progesterone treatment. Br Vet J 147:469–477

    Article  CAS  PubMed  Google Scholar 

  27. Roark DB, Herman HA (1950) Physiological and histological phenomena of the bovine estrual cycle with special reference to vaginal-cervical secretions. Research Bulletin, vol 455, Missouri Agricultural Experiment Station. University of Missouri College of Agriculture, Columbia, MO

    Google Scholar 

  28. Hamilton WJ, Harrison RJ (1970) Cyclical changes in the uterine mucosa and vagina of the goat. J Anat 85:316–326

    Google Scholar 

  29. Wilson KM (1926) Histological changes in vaginal mucosa of sow in relation to the estrous cycle. Am J Anat 37:417–426

    Article  Google Scholar 

  30. Boyland E (1946) The composition of bovine cervical mucins and their reaction with oxidizing agents. Biochem J 40:334–337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kanagawa H, Hafez ES, Pitchford WC, Baechler CA, Barnhart MI (1972) Surface patterns in the reproductive tracts of the rabbit observed by scanning electron microscopy. Anat Rec 174:205–225

    Article  CAS  PubMed  Google Scholar 

  32. Vickery BH, Bennett JP (1968) The cervix and its secretion in mammals. Physiol Rev 48:135–154

    Article  CAS  PubMed  Google Scholar 

  33. Egli GE, Newton M (1961) The transport of carbon particles in the human female reproductive tract. Fertil Steril 12:151–155

    Article  CAS  PubMed  Google Scholar 

  34. Woodman HE, Hammond J (1925) The mucous secretion of the cervix of the cow. J Agr Sci 15:107–124

    Article  CAS  Google Scholar 

  35. Gibbons RA (1959) Chemical properties of two mucoids from bovine cervical mucin. Biochem J 73:209–217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Gibbons RA, Glover FA (1959) The physicochemical properties of two mucoids from bovine cervical mucin. Biochem J 73:217–225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Wagner G, Levin RL (1984) Human vaginal pH and sexual arousal. Fertil Steril 41:389–394

    Article  CAS  PubMed  Google Scholar 

  38. Hamana K, El-Banna AA, Hafez ESE (1971) Sialic acid and some physico-chemical characteristics of bovine cervical mucus. Cornell Vet 61:104–113

    CAS  PubMed  Google Scholar 

  39. Scott Blair GW, Folley SJ, Malpress FH, Coppen FMV (1941) Variations in certain properties of bovine cervical mucus during the oestrous cycle. Biochem J 35:1039–1110

    Article  Google Scholar 

  40. Herrick JB (1951) The cytological changes in the cervical mucosa of the cow (Bos taurus) throughout the estrous cycle. Am J Vet Res 12:276–283

    CAS  PubMed  Google Scholar 

  41. Moghissi KS, Neuhaus OW (1962) Composition and properties of human cervical mucus II. Immunoelectrophoretic studies of the proteins. Am J Obstet Gynecol 83:149–155

    Article  CAS  PubMed  Google Scholar 

  42. Rozansky R, Persky S, Bercovici B (1962) Antibacterial action of cervical mucus. Proc Soc Exp Biol Med 110:876–881

    Article  CAS  PubMed  Google Scholar 

  43. Mattner PE (1969) Phagocytosis of spermatozoa by leucocytes in bovine cervical mucus in vitro. J Reprod Fertil 20:133–134

    Article  CAS  PubMed  Google Scholar 

  44. Rathbone MJ, Raj-Bista S, Haywood A (2009) Design and development of long acting intravaginal veterinary products: physical characterisation of the vaginal cavity of farmed animals. Proc Int Symp Controlled Release Bioact Mater

    Google Scholar 

  45. Burns PJ (2011) New techniques in hormonal delivery. In: McKinnon A, Squires E, Vaala W, Varner D (eds) Equine reproduction, Chap. 198, 2nd edn. Blackwell Publishing Ltd, Malden, MA, pp 1879–1887

    Google Scholar 

  46. Burggraaf S, Rathbone MJ, Day B, Bunt CR, Ogle CR (1999) Development of a progesterone-containing intravaginal insert to control the estrus cycle in gilts. Proc Int Symp Controlled Release Bioact Mater 26:146

    Google Scholar 

  47. Rathbone MJ, Bunt CR, Ogle CR, Burggraaf S, Ogle C, Macmillan KL, Burke CR, Pickering KL (2002) Reengineering of a commercially available bovine intravaginal insert (CIDR insert) containing progesterone. J Control Release 85:105–115

    Article  CAS  PubMed  Google Scholar 

  48. Rathbone MJ, Bunt CR, Burggraaf S, Burke CR, Macmillan KL (1998) Optimization of a controlled release intravaginal drug delivery system containing progesterone for the control of estrus in cattle. Proc Int Symp Controlled Release Bioact Mater 25:249–250

    Google Scholar 

  49. Ogle CR (1999) Design, development and optimisation of veterinary intravaginal controlled release drug delivery systems. University of Waikato, Hamilton, NZ

    Google Scholar 

  50. Rathbone MJ, Bunt CR, Ogle CR, Burggraaf S, Ogle C, Macmillan KL, Pickering KL (2002) Development of an injection molded poly (ε-caprolactone) intravaginal insert for the delivery of progesterone to cattle. J Control Release 85:61–71

    Article  CAS  PubMed  Google Scholar 

  51. Ogle CR, Rathbone MJ, Smith JF, Bunt CR, Burggraaf S, Pickering KL (1999) Development of an injection moldable, biodegradable intravaginal insert technology. Proc Int Symp Controlled Release Bioact Mater 26:143

    Google Scholar 

  52. Bunt CR, Woodward VG, Rathbone MJ, Burggraaf S, Ogle CR, Burke CR, Pickering KL (1999) A poly (e-caprolactone) bovine intravaginal insert for the delivery of progesterone. Proc Int Symp Controlled Release Bioact Mater 26:145

    Google Scholar 

  53. Grimmett JB, Hanlon DW, Duirs GF, Jochle W (2002) A new intra-vaginal progesterone-releasing device (Cue-MareTM) for controlling the estrous cycle in the mare. Theriogenology Suppl, 58:585–587

    Google Scholar 

  54. http://www.agrihealth.co.nz/

    Google Scholar 

  55. Bó GA, Tegli J, Cutaia L, Moreno D, Alisioy L, Tríbulo R (2000) Fixed-time artificial insemination in braford cows treated with progesterone releasing devices and eCG or estradiol benzoate. Proc XV Reunión Anual de la Sociedad Brasilera de Tecnología Embrionaria, Caldas Novas, Goiâs, Brasil. Arq Fac Vet UFRGS, vol 28, p 209

    Google Scholar 

  56. Bunt CR, Rathbone MJ, Burggraaf S, Ogle CR (24) Development of a QC release assessment method for a physically large veterinary product containing a highly water insoluble drug and the effect of formulation variables upon release. Proc Int Symp Controlled Release Bioact Mater 24:145–146

    Google Scholar 

  57. Bunt CR, Rathbone MJ, Burggraaf S, Macmillan KL, Rhodes F (1997) Factorial analysis of the effect of surface area and drug load on the release rate of progesterone from a controlled release intravaginal drug delivery system. Proc Intern Symp Control Release Bioact Mater 24:743–744

    Google Scholar 

  58. Burggraaf S, Rathbone MJ, Bunt CR, Burke CR, Pickering KL (1997) Effect of silicone shore hardness, inert fillers and progesterone particle size upon the release of progesterone from a controlled release intravaginal drug delivery system. Proc Intern Symp Control Release Bioact Mater 24:147–148

    Google Scholar 

  59. Heredia V, Bianco ID, Trıbulo H, Cuesta G, Chesta P, Bo GA, Trıbulo R, Mega VI, Beltramo DM (2008) Room temperature vulcanizing silicone sheaths on a reusable support for progesterone delivery in estrous synchronization treatments in cattle. Anim Reprod Sci 108:356–363

    Article  CAS  PubMed  Google Scholar 

  60. Bunt CR, Rathbone MJ, Burggraaf S, Ogle CR, Burke CR (1999) Elevation of plasma progesterone levels in cattle using a poly (e-caprolactone) and cyclodextrin intravaginal insert containing progesterone. Proc Int Symp Controlled Release Bioact Mater 26:6705

    Google Scholar 

  61. Bunt CR, Rathbone MJ, Ogle CR, Morgan S (2) An electronically modulated bovine intravaginal device for the delivery of progesterone. Proc Int Symp Controlled Release Bioact Mater, p 28

    Google Scholar 

  62. Bunt CR, Rathbone MJ, Burggraaf S (1998) Controlled electrolysis of water in a hydrogel matrix to dispense liquids. Proc Int Symp Controlled Release Bioact Mater 25:62–63

    Google Scholar 

  63. Bunt CR, Rathbone MJ, Burggraaf S (1988) Controlled electrolysis of water in a hydrogel matrix to dispence liquids from an infusion device. American Association of Pharmaceutical Scientists Annual Meeting, PharmSci Suppl (1):96

    Google Scholar 

  64. Bunt CR, Rathbone MJ, Burggraaf S (1998) Controlled electrolysis of water in a hydrogel matrix to dispense liquids from an infusion device. American Association of Pharmaceutical Scientists Annual Meeting, PharmSci Suppl (1):96

    Google Scholar 

  65. Rathbone M, Bunt C, Ogle C (2002) Simultaneous sustained progesterone and pulsatile estradiol benzoate delivery from an electronically modulated bovine intravaginal insert. Proc Int Symp Controlled Release Bioact Mater, p 29

    Google Scholar 

  66. Künnemeyer R, Cross PS, Bunt CR, Carnegie DA, Rathbone MJ, Claycomb RW (2003) Oestrus detection and automated oestrus control in dairy cows using telemetry. Electronics New Zealand Conference, Hamilton, NZ

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael J. Rathbone .

Editor information

Editors and Affiliations

Additional information

This chapter is dedicated to my friend and colleague Patrick J. Burns who passed away last year. A leader in the field of estrous control, he will forever be admired by me for his imagination, tenacity, knowledge and friendship.

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Controlled Release Society

About this chapter

Cite this chapter

Rathbone, M.J., Burke, C.R. (2013). Controlled Release Intravaginal Veterinary Drug Delivery. In: Rathbone, M., McDowell, A. (eds) Long Acting Animal Health Drug Products. Advances in Delivery Science and Technology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4439-8_11

Download citation

Publish with us

Policies and ethics