Influence of the dissolution medium on the release of dehydroepiandrosterone from lipophilic suppositories

Open access


Suppositories with cocoa butter containing dehydroepiandrosterone (DHEA) without and with the addition of Span 80 and Tween 80 as surfactants with low and high HLB values were prepared. The physical properties and the drug content of all prepared suppositories were in accordance with the pharmacopoeial requirements. The release study tests in three dissolution media such as water, lactic acid solution at pH 4.2 and phosphate buffer at pH 7.4 were carried out. In acidic and alkalic media only about 10% and 27% of DHEA were released, respectively. The addition of Span 80 to the suppository mass did not improve the release process, but the addition of Tween 80 caused the increase in the amount of DHEA released in the acidic medium to about 35%. The data showed that rectal administration of suppositories with DHEA based on cocoa butter caused about 30% availability and after vaginal administration, only topical activity can be expected. By the addition of Tween 80 to the suppository mass availability of DHEA of about 35% from vaginal suppositories can be achieved.

1. Azarmi S. et al.: Current perspectives in dissolution testing of conventional and novel dosage forms. Int. J. Pharm., 328(1), 12, 2007.

2. Babar A., Fares H. M., Plakogiannis F. M.: In vitro release of testosterone from suppository bases and in vivo absorption studies in human males. J. Pharm. Sci., 82(4), 389, 1993.

3. Beral V., Bull D., Reeves G.: Endometrial cancer and hormonereplacement therapy in the Million Women Study. Lancet, 365, 1543, 2005.

4. Bergogne-Bérézin E., Bryskier A.: The suppository form of antibiotic administration: pharmacokinetics and clinical application.J. Antimicrob. Chemother., 43(2), 177, 1999.

5. Buster J.E., Casson P.R. (2000). Biology and use in therapeutic intervention. in Menopause: Biology and Pathobiology. Lobo R. A., Kelsey J. and Marcus R. (editors). San Diego: Academic Press; p 628.

6. Casson P. R. et al.: Dehydroepiandrosterone (DHEA) replacement in postmenopausal women: Present status and future promise.Menopause, 4, 225, 1997.

7. Casson P. R. et al.: Oral dehydroepiandrosterone in physiologic doses modulates immune function in postmenopausal women. Am.J. Obstet. Gynecol., 169, 1536, 1993.

8. Casson P. R. et al.: Replacement of dehydroepiandrosterone enhances T-lymphocyte insulin binding in postmenopausal women. Fertil Steril, 63(5), 1027, 1995.

9. Castelo-Branco C. et al.: Management of post-menopausal vaginal atrophy and atrophic vaginitis. Maturitas, 52(Suppl. 1), 46, 2005.

10. Chicco D. et al.: Correlation of in vitro and in vivo paracetamol availability from layered excipient suppositories. Int. J. Pharm., 189, 147, 1999.

11. Czarnecki W., Kasperek R.: Patent RP Nr P337979 z 21.01.2000r.Biomed Wytwórnia Surowic i Szczepionek w Lublinie.

12. Dal Zorro M. et al.: Effect of the surfactant on the availability of piroxicam as a poorly hydrosoluble drug from suppositories.Pharmazie, 67(1), 37, 2012.

13. Ghorab D., Refai H., Tag R.: Preparation and evaluation of fenoterol hydrobromide suppositories. Drug Discov. Ther., 5(6), 311, 2011.

14. Hargoli S. et al.: Preparation and In vitro Evaluation of Naproxen Suppositories. Indian J. Pharm. Sci., 75(2), 143, 2013.

15. Kalmár É. et al.: Novel sample preparation method for surfactant containing suppositories: effect of micelle formation on drug recovery. J. Pharm. Biomed. Anal., 83, 149, 2013.

16. Karavana S. Y. et al.: Dissolution and histological studies on ordidazole vaginal formulation. Acta Pharma. Sci., 52, 430, 2010.

17. Labrie F. et al.: Effect of intravaginal dehydroepiandrosterone (Prasterone) on libido and sexual dysfunction in postmenopausal women. Menopause, 16(5), 923, 2009.

18. Labrie F. et al.: Intravaginal dehydroepiandrosterone (prasterone), a highly efficient treatment of dyspareunia. Climacteric, 14(2), 282, 2011.

19. Labrie F. et al.: Intravaginal dehydroepiandrosterone (Prasterone), a physiological and highly efficient treatment of vaginal atrophy.Menopause, 16(5), 907, 2009.

20. Labrie F. et al.: Is Dehydroepiandrosterone a hormone? J. Endocrinol., 187,169, 2005.

21. Labrie F. et al.: Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging. J. Clin. Endocrinol. Metab., 82, 2396, 1997.

22. Lynch C.: Vaginal estrogen therapy for the treatment of atrophic vaginitis. J. Womens Health (Larchmt), 18(10), 1595, 2009.

23. Nestler J. E. et al.: Dehydroepiandrosterone reduces serum low density lipoprotein levels and body fat but does not alter insulin sensitivity in normal men. J. Clin. Endocrinol. Metab., 66, 57, 1988.

24. Niraj et al.: Effect of Adjuvants on the Release Pattern of Suppositories Containing Paracetamol. RJCES, 1(1), 19, 2013.

25. Odeniyi M. A., Jaiyeoba K. T.: Effects of interacting variables on the release properties of chloroquine and aminophylline suppositories.Trop. J. Pharm. Res., 3(1), 285, 2004.

26. Panjari M., Davis S.R.: DHEA for postmenopausal women: a review of the evidence. Maturitas, 66(2), 172, 2010.

27. Panjari M., Davis S.R.: Vaginal DHEA to treat menopause related atrophy: a review of the evidence. Maturitas, 70(1), 22, 2011.

28. Polish Pharmacopoeia IXth ed., vol. I, PTF Warsaw (2011).

29. Realdon N. et al.: Effects of surfactant characteristics on drug availability from suppositories. Pharmazie, 63(6), 459, 2008.

30. Sah M. L., Saini T.R.: Formulation development and release studies of indomethacin suppositories. Indian J. Pharm. Sci., 70(4), 498, 2008.

31. Varshney H. M., Chatterjee A.: Formulation, evaluation and in-vitro release characteristics of zaltoprofen suppositories. Asian J. Pharm.Clin. Res., 5(4), 235, 2012.

32. Varshney H. M., Tanwar Y. S.: Effect of different surfactants on the release pattern of cocoa butter suppositories containing flurbiprofen sodium. Acta Pharm. Sci., 52, 129, 2010.

33. Verma P. et al.: Routes of drug administration. Int. J. Pharm. Studies Res., 1(1), 54, 2010.

Current Issues in Pharmacy and Medical Sciences

Formerly Annales UMCS Sectio DDD Pharmacia

Journal Information

CiteScore 2016: 0.19

SCImago Journal Rank (SJR) 2016: 0.132
Source Normalized Impact per Paper (SNIP) 2016: 0.119


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 55 55 20
PDF Downloads 13 13 6