Návrh a vývoj systému pro transmukózní přívod diltiazem hydrochloridu

Diltiazem hydrochlorid je antihypertenzní látka, která vykazuje značný first pass metabolismus, a to ji činí vhodným kandidátem pro bukální podání. Mukoadhezivní bukální náplasti byly připraveny s HPMC, chitosanem, PVP, PVA a carbopolem. Fyzikálně-chemické interakce mezi léčivem a polymery byly sledovány pomocí FTIR a DSC: stanovení neprokázala žádné interakce mezi diltiazem hydrochloridem a polymery. U bukálních náplastí se stanovily různé fyzikálně-chemické parametry, uvolňování léčiva in vitro a permeace ex vivo přes bukální sliznici prasete. Zbytkové obsahy rozpouštědel v náplastech se určily plynovou chromatografií a byly pod tolerovanými limity. Při ex vivo studii se léčivo z náplastí uvolňovalo rovnoměrně po dobu 12 hodin kinetickým modelem podle Korsmeyer-Peppase. Stabilita optimalizované formulace se zkoumala podle pokynů ICH a z hlediska obsahu léčiva a jeho permeace ex vivo vykazovala výborné výsledky.

Klíčová slova:
diltiazem hydrochlorid • bukální náplasti • bytková rozpouštědla • mukoadheze, uvolňování léčiva in vitro • permeace ex vivo

Autoři: Subhash Chandra Bose Penjuri; Saritha Damineni; Nagaraju Ravouru
Vyšlo v časopise: Čes. slov. Farm., 2013; 62, 19-27
Kategorie: Původní práce

Souhrn

Klíčová slova:
diltiazem hydrochlorid • bukální náplasti • bytková rozpouštědla • mukoadheze, uvolňování léčiva in vitro • permeace ex vivo

Zdroje

1. Aungst B. J., Rogers M. J., Shefter E. Comparison of nasal, rectal, buccal, sublingual and intramuscular Insulin efficacy and the effects of a bile salt as absorption promoter. The J Pharmacol Exp Ther. 1998; 244, 23–27.

2. Lee W. E. Permeation enhancers for nasal drug delivery of protein and peptide therapeutics. Biopharm. 1990; 3, 22–25.

3. Soyani A. P., Chein Y. W. Systemic delivery of peptides and proteins across absorptive mucosae. Crit Rev Therapy: Drug Carries System. 1996; 13, 85–184.

4. Rathbone M. J., Hadgraft J. Absorption of drugs from the human oral cavity. Int J Pharm. 1991; 74, 9–24.

5. Squier C. A. The permeability of oral mucosa. Crit Rev Oral Biol Med. 1991; 2, 13–32.

6. Gandhi R. E., Robinson J. R. Bioadhesion in drug delivery. Ind J Pharm Sci. 1998; 50, 145–152.

7. Saisavam S., Muhammed M. H. Design and evaluation of Diltiazem Hydrochloride buccal patches. Ind J Pharm Sci. 2000; 62, 236–238.

8. Verma P. R. P., Sunil S. I. Transdermal Delivery of Propranolol Using Mixed Grades of Eudragit: Design and in vitro and in vivo Evaluation. Drug Dev Ind Pharm. 2000; 26, 471–476.

9. Pavankumar G. V., Ramakrishna V., William G. J., Konde A. Formulation and evaluation of buccal films of Salbutamol sulphate. Indian J Pharm Sci. 2005; 67, 160–164.

10. Khanna R., Agarwal S. P., Ahuja A. Preparation and evaluation of buccal films of clotrimazole for oral candida infections. Indian J Pharm Sci. 1997; 59, 299–305.

11. Nafee N. A., Boraie N. A., Ismail F. A., Mortada L. M. Mucoadhesive delivery systems II. Formulation and in vitro/ in vivo evaluation buccal mucoadhesive tablets containing water soluble drugs. Drug Dev Ind Pharm. 2004; 30, 995–1004.

12. Ilango R., Kavimani S., Mullaichasam A. R., Jayakar B. In vitro studies on buccal strips of Glibenclamide using chitosan. Indian J Pharm Sci. 1997; 59, 232–235.

13. Kulkarni U., Mahalingam R., Pather S. I., Li X., Jasti B. Porcine Buccal Mucosa as an In Vitro Model: Relative Contribution of Epithelium and Connective Tissue as Permeability Barriers. J Pharm Sci. 2009; 98, 471–483.

14. Metia P. K., Bandyopadhyay A. K. In vitro Evaluation of Novel Mucoadhesive Buccal Tablet of Oxytocin Prepared with Diospyros Peregrina Fruits Mucilages, Yakugaku Zasshi. 2008; 128, 603–609.

15. Agarwal V., Mishra B. Design, Development, and Biopharmaceutical Properties of Buccoadhesive Compacts of Pentazocine. Drug Dev Ind Pharm. 1999; 25, 701–709.

16. Puranik S. B., Varun Pawar R., Lalitha N., Pai P. N., Rao G. K. Residual Solvent Analysis in Hydrochloride Salts of Active Pharmaceutical Ingredients. Pak J Pharm Sci. 2009; 22, 410–414.

17. Stackler B., Christensen E. N. Quantitative Determination of Ethanol in Wine by Gas Chromatography. Amer J Enol Viticult. 1974; 25, 202–207.

18. Robert Schubert B. S., Ketel L. Gas Chromatographic Determination of Methylene Chloride in Aerosol air Sprays. J Soc Cosmet Chem. 1972; 23, 115–124.

19. Kratochvil J., Holas J. A gas chromatographic method for the determination of acetic acid and lactic acid in rye sour. Cereal Chem. 1980; 57, 209–211.

20. Al Saidan S. M., Krishnaiah Y. S., Patro S. S., Satyanaryana V. In Vitro and In Vivo Evaluation of Guar Gum Matrix Tablets for Oral Controlled Release of Water-soluble Diltiazem Hydrochloride. AAPS Pharm Sci Tech. 2005; 6 (1) Article 5.

http://www.aapspharmscitech.org.

21. Patel V. M., Prajapati B. G., Patel J. K., Patel M. M. Design and characterization of chitosan-containing mucoadhesive buccal patches of propranolol hydrochloride. Acta Pharm. 2007; 57, 61–72.

22. Shojaei A. H., Zhou S. L., Li X. Transbuccal Delivery of Acyclovir (II): Feasibility, System Design, and In Vitro Permeation Studies. J Pharm Pharmaceut Sci. 1998; 1, 66–73.

23. Maurya S. K., Bali V., Pathak K. Bilayered transmucosal drug delivery system of pravastatin sodium: Statistical optimization, in vitro, ex vivo, in vivo and stability assessment. Drug Delivery. 2012; 19, 45–57.

24. Vasantha P. V., Puratchikody A., Mathew S. T., Balaraman A. K. Development and characterization of Eudragit based mucoadhesive buccal patches of salbutamol sulfate. Saudi Pharmaceutical Journal. 2011; 19, 207–214.

25. Palem C. R., Gannu R., Doodipala N., Yamsani V. V., Yamsani M. R. Transmucosal Delivery of Domperidone from Bilayered Buccal Patches: In Vitro, Ex Vivo and In Vivo Characterization. Arch Pharm Res. 2011; 34, 1701–1710.

26. Saranjit Singh. Drug stability testing and shelf-life determination according to international guidelines. Pharmaceutical technology. 1999; 23, 68–88.

27. Chang H. S., Park H., Robinson J. R. Bioadhesive polymers as platform for oral controlled drug delivery: II, synthesis and evaluation of some swelling, water insoluble bioadhesive polymers. J. Pharm. Sci. 1985; 74, 399–405.

28. Park H., Robinson J. R. Physico chemical properties of water insoluble polymers important to mucin epithelial adhesion. J. Control. Rel. 1985; 2, 47–57.

29. Shidhaye S. S., Saindane N. S., Sutar S., Kadam V. Mucoadhesive Bilayered Patches for Administration of Sumatriptan Succinate. AAPS PharmSciTech. 2008; 9, 1–8.

30. Sakellariou P. A study of the leaching/retention of watersoluble polymers in blends with ethylcellulose using torsional braid analysis. J. Control. Rel. 1998; 7, 147–157.

31. Nappinnai M., Chandanbala R., Balaijirajan R. Formulation and Evaluation of Nitrendipine Buccal Films. Indian J Pharm Sci. 2008; 70, 631–635.

32. Satishbabu B. K., Srinivasan B. P. Preparation and Evaluation of Buccoadhesive Films of Atenolol. Indian J Pharm Sci. 2008; 70, 175–179.

33. Hao J. S., Chan L. W., Shen Z. X., Heng P. W. Complexation between PVP and Gantrez polymer and its effect on release and bioadhesive properties of the composite PVP/Gantrez films. Pharm Dev Technol. 2004; 9, 379–386.

34. Nafee N. A., Boraie N. A., Ismail F. A., Mortada L. M. Mucoadhesive buccal patches of miconazole nitrate: in vitro/in vivo performance and effect of ageing. Int J Pharm. 2003; 264, 1–14.

35. Patel V. M., Prajapati B. G., Patel M. M. Effect of hydrophilic polymers on buccoadhesive eudragit patches of Propranolol hydrochloride using factorial design. AAPS PharmSciTech. 2007; 8 (2) Article 45. http://www.aapspharmscitech.org.

36. Chary C. B., Vani G., Rao Y. M. In vitro and in vivo adhesion testing of mucoadhesive drug delivery systems. Drug Dev Ind Pharm. 1999; 25, 685–690.

37. Yehia S. A., El Gazayerly O. N., Basalious E. B. Fluconazole Mucoadhesive Buccal Films: In vitro/In Vivo Performance. Curr Drug Deliv. 2009; 6, 17–27.

38. Lee H. Y., Wu P. C., Lee Y. J. Stab: An R package for drug stability data analysis. Compu methods and programs in biomed. 2010; 100, 140–148.