Advances in Traditional Medicine

Kyung Hee Oriental Medicine Research Center (경희대학교 융합한의과학연구소)
권호 표지
DOI QR코드

DOI QR Code

In vitro and in vivo studies on theophylline mucoadhesive drug delivery system

  • Bandyopadhyay, AK (Department of pharmaceutical Technology, Division of Pharmaceutics, Jadavpur University) ;
  • Perumal, P (Bioequivalence and Analytical Research Laboratory, JKK Nataraja College of Pharmacy)
  • Published : 2007.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

Mucus is an aqueous gel complex with a constitution of about 95% water, high molecular weight glycoprotein (mucin), lipid, salts etc. Mucus appears to represent a significant barrier to the absorption of some compounds. Natural mucoadhesive agent was isolated and purified from the aqueous extract of the seeds of prosopis pallida (PP). Formulated tablet with the isolated material by wet granulation method. Some natural edible substances are in consideration for candidates as mucoadhesive agents to claim more effective controlled drug delivery as an alternative to the currently used synthetic mucoadhesive polymers. Subjected the materials obtained from natural source i.e. PP and standard synthetic substance, sodium carboxymethyl cellulose for evaluation of mucoadhesive property by various in vitro and in vivo methods. Through standard dissolution test and a model developed with rabbit, evaluated in vitro controlled release and bioadhesive property of theophylline formulation. Mucoadhesive agent obtained from PP showed good mucoadhesive potential in the demonstrated in vitro and in viνo models. The results suggest that the mucoadhesive agent showed controlled release properties by their application, substantially. In order to assess the gastrointestinal transit time in vivo, a radio opaque X-ray study performed in healthy rabbit testing the same controlled release formulation with and without bioadhesive polymer. Plasma levels of theophylline determined by the HPLC method and those allowed correlations to the in vitro mucoadhesive study results. Better correlation found between the results in different models. PP may acts as a better natural mucoadhesive agent in the extended drug delivery system.

Keywords

References

  1. Ahuja A, Khar RK, Ali J. (1997) Mucoadhesive drug delivery systems. Drug Dev. Ind. Pharm. 23, 489-515
  2. Akiyama Y, Nagahara N, Kashihara T, Hirai S, Toguchi H. (1995) In vitro and in vivo evaluation of mucoadhesive microspheres prepared for the gastrointestinal tract using polyglycerol esters of fatty acids and a poly(acrylic acid) derivative. Pharm. Res. 12, 397-405 https://doi.org/10.1023/A:1016208703380
  3. ASTM Designation D. (1984) American Society for Testing and Materials, Philadelphia, 907-977
  4. Banerjee AK, Perumal P. (2004) Charecterisation and in vitro evaluation of some natural mucoadhesive agents. Int. J. Chem. Sci. 2, 171-182
  5. Burjak M, Bogataj M, Velnar M, Grabnar I, Mrhar A. (2001) The study of drug release from microspheres adhered on pig vesical mucosa. Int. J. Pharm. 224, 123-130 https://doi.org/10.1016/S0378-5173(01)00748-7
  6. Carreno-Go'mez B, Woodley JF, Florence AT. (1999) Studies on the uptake of tomato lectin nanoparticles in everted gut sacs. Int. J. Pharm. 183, 7-11 https://doi.org/10.1016/S0378-5173(99)00050-2
  7. 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 https://doi.org/10.1002/jps.2600740407
  8. Chen JL, Cyr GN. (1970) Compositions producing adhesion through hydration (Chapter 10). In: Adhesion in biological systems; Manly, RS., 163-181, Ed.; Academic press, Inc.: New York
  9. Chickering III DE, Jacob JS, Desai TA, Harrison M, Harris WP, Morrell CN, Chaturvedi P. (1997) Bioadhesive microspheres: III. An in vivo transit and bioavailability study of drug-loaded alginate and poly(fumaric-cosebacic anhydride) micro spheres. J. Control Rel. 48, 35-46 https://doi.org/10.1016/S0168-3659(97)00054-0
  10. Chickering III DE, Jacob JS, Mathiowitz E. (1995) Bioadhesive microspheres: II. Characterization and evaluation of bioadhesion involving hard, bioerodible polymers and soft tissue, React. Polym. 25, 189-206 https://doi.org/10.1016/0923-1137(94)00098-P
  11. Cuna M, Alonso MJ, Torres D. (2001) Preparation and in vivo evaluation of mucoadhesive microparticles containing amoxicillin-resin complexes for drug delivery to the gastric mucosa. Eur. J. Pharm. Biopharm. 51, 199-205 https://doi.org/10.1016/S0939-6411(01)00124-2
  12. Dabbagh MA, Ford JL, Rubinstein JE, Hoga AR, Rajabi S. (1999) Release of propranolol hydrochloride from matrix tablets containing sodium carboxymethycellulose. Pharm. Dev. Tech. 4, 313-324 https://doi.org/10.1081/PDT-100101367
  13. Davis 55, Hardy JG, Taylor MJ, Whalley DR, Wilson CG. (1984) The effect of food on the gastrointestinal transit of pellets and osmotic device (Osmet). Int. J. Pharm. 21, 331-340 https://doi.org/10.1016/0378-5173(84)90191-1
  14. Davis SS, Hardy JG, Fara JW. (1986) Transit of pharmaceutical dosage forms through the small intestine. Gut 27, 886-892 https://doi.org/10.1136/gut.27.8.886
  15. Digenis GA, Sandefer EP. (1991) Gamma scintigraphy and neutron activation techniques in the in vivo assessment of orally administered dosage forms. Crit. Rev. Ther. Drug Carrier Sys. 7, 309-345
  16. Dobrozsi DJ, Smith RL, Sakr AA. (1999) Comparative mucoretention of sucralfate suspensions in an everted rat esophagus model. Int. J. Pharm. 189,81-89 https://doi.org/10.1016/S0378-5173(99)00244-6
  17. Duhene D, Touchard F, Peppas NA. (1988) Pharmaceutical and medical aspects of bioadhesive systems for drug administration. Drug. Dev. Ind. Pharm. 14,283-318
  18. Gandhi RB, Robinson JR. (1988) Bioadhesion in drug delivery. Indian J. Pharm. Sci. 50, 145-152
  19. Good RJ. (1976) On the definition of Adhesion. J. Adhesion 8, 1 https://doi.org/10.1080/00218467608075066
  20. Gu JM, Robinson JR, Leung SHS. (1988) Binding of acrylic polymers to mucin epithelial surfaces - Stucture - Property relationships. Crit. Rev. Ther. Drug Carrier Syst. 5, 21-67
  21. Gupta PK, Leung SHS, Robinson JR (1990) Bioadhesives/mucoadhesives in drug delivery to the gastrointestinal tract. In: Bioadhesive Drug Delivery Systems; Lenaerts V, Gumy R, 65-92, Ed.; CRC Press, Inc.: Boca Raton
  22. Gurny R,Meyer JM, Peppas NA. (1984) Bioadhesive intraoral release systems: design, testing and analysis. Biomaterials 5, 336-340 https://doi.org/10.1016/0142-9612(84)90031-0
  23. Hendeles, L, Weinberger MJ. (1986) Selection of a slow release theophylline product. Allergy Gin. Immunol. 78, 743-751
  24. Hussain AS, Johnson RD, Shivanand P, Zoglio MA. (1994) Effects of blending a non-ionic and an nionic cellulose ether polymer on drug release from hydrophilic matrix capsules. Drug Dev. Ind. Pharm. 20, 2645-2657
  25. Iscan YY, Capan Y, Senel S, Sahin MF, Kes S, Duchene D, Hincal AA. (1998) Formulation and in vitro/in vivo evaluation of buccal bioadhesive captopril tablets. S.T.P. Pharma Sci. 8,357-363
  26. Jaspreet KV, Kaustubh TW, Sanjay G. (2003) Bioadhesive microspheres as a controlled drug delivery system. Int. J. Pharm, 255, 13-32 https://doi.org/10.1016/S0378-5173(03)00087-5
  27. Jime'nez-Castellanos RM, Zia H, Rhodes CT. (1993) Mucoadhesive drug delivery systems. Drug Dev. Ind. Pharm. 19, 143-194
  28. Kamath KR, Park K. (1994) Mucosal adhesive preparations. In Encyclopedia of Pharmaceutical Technology; Swarbrick J, Boylan JC, 10, 133-163, Ed.; Marcel Dekker, Inc., New York
  29. Khalid MT, Ch'ng HS. (1998) Evaluation of possible mechanism(s) of bioadhesion. Int. J. Pharm, 160, 61-74 https://doi.org/10.1016/S0378-5173(97)00297-4
  30. Kortiz GD, McKiernan BC, Neff-Davis CA, Munsiff IJ. (1986) Bioavailability of four slow-release theophylline formulations in the beagle dog. J. Vet. Pharmacol. Ther. 9, 293-302
  31. Kulkarini GT, Gowthamarajan K, Rao BG, Suresh B. (2002) Evaluation of binding properties of plantago ovata and trigonella foenum graecum mucilages. Indian drugs 39, 422-425
  32. Lehr, CM. (1996) From sticky stuff to sweet receptors, achievements, limits and novel approaches to bioadhesion. Eur. J. Drug Metab. Pharmacokinet. 21, 139-148
  33. Lehr CM, Bouwstra JA, Schacht EH, Junginger HE. (1992) In vitro evaluation of mucoadhesive properties of chitosan and some other natural polymers. Int. J. Pharm. 78, 43-48 https://doi.org/10.1016/0378-5173(92)90353-4
  34. Lehr CM, Bouwstra JA, Tukker JJ, Junginger HE. (1990) Intestinal transit of bioadhesive microspheres in an in situloop in the rat - a comparative study with copolymers and blends bases on poly(acrylic acid). J. Control Rel. 13, 51-62 https://doi.org/10.1016/0168-3659(90)90074-4
  35. Longer MA, Robinson JR. (1986) Fundamental aspects of bioadhesion. Pharm. Int. 7, 114-117
  36. Mikos AG, Peppas NA. (1986) Comparison of experimental technique for the measurement of the bioadhesive forces of polymeric materials with soft tissues. Proc. Int. Symp. Control Rel. Bloact. Mater. 13, 97
  37. Mikos AG, Peppas NA. (1986) Systems for controlled release of drugs V. Bioadhesive systems. S.T.P. Pharma Sci. 2, 705-716
  38. Miyazaki Y, Ogihara K, Yakou S, Nagai T, Takayama K (2003) In vitro and in vivo evaluation of mucoadhesive microspheres consisting of dextran derivatives and cellulose acetate butyrate. Int. J. Pharm. 258, 21-29 https://doi.org/10.1016/S0378-5173(03)00159-5
  39. Mortazavi SA. (1995) An in vitro assessment of mucus/mucoadhesive interactions. Int. J. Pharm. 124, 173-182 https://doi.org/10.1016/0378-5173(95)00073-R
  40. Nagahara N, Akiyama Y, Nakao M, Tada M, Kitano M, Ogawa Y. (1998) Mucoadhesive microspheres containing amoxicillin for clearance of Helicobacter pylori. Antimicrob. Agents Chemother. 42, 2492-2494
  41. Nagai T, Machida Y. (1985) Advances in Drug delivery. Mucosal adhesive dosage forms. Pharm. Int. 6, 196-200
  42. ？Nikolaos AP, Jennifer JS. (1996) Hydrogels as mucoadhesive and bioadhesive materials: a review. Biomaterials 17, 1553-1561 https://doi.org/10.1016/0142-9612(95)00307-X
  43. Park H, Robinson JR (1985) Physico-chemical properties of water insoluble polymers important to mucin epithelial adhesion. J. Control Rel. 2, 47-57 https://doi.org/10.1016/0168-3659(85)90032-X
  44. Park K, Robinson JR. (1984) Bioadhesive polymers as platforms for oral controlled drug delivery method to study Bioadhesion. Int. J. Pharm. 19, 107-127 https://doi.org/10.1016/0378-5173(84)90154-6
  45. Peppas NA, Buri PA. (1985) Surface, Interfacial and molecular aspects of polymer bioadhesion on soft tissues. J. Control Rel. 2, 257-275 https://doi.org/10.1016/0168-3659(85)90050-1
  46. Peppas NA, Buri P A. (1985) Surface, interfacial and molecular aspects of polymers bioadhesion on soft tissues. J. Control Rel. 2, 257-275 https://doi.org/10.1016/0168-3659(85)90050-1
  47. Rao KVR, Buri PA. (1989) Novel in situ method to test polymers and coated micro particles for Bioadhesion. Int. J. Pharm. 52, 265-270 https://doi.org/10.1016/0378-5173(89)90229-9
  48. Rao YM, Vani G, Balarameshacharry R. (1998) Design and Evaluation of mucoadhesive drug delivery systems. Indian Drugs 35, 559-561
  49. Reilly SO, Wilson CG, Hardy JG. (1987) The influence of food on the gastric emptying of multiparticulate dosage forms. Int. J. Pharm. 34, 213-216 https://doi.org/10.1016/0378-5173(87)90182-7
  50. Richardson JL, Whetstone J, Fisher AN, Watts P, Farraj NF. (1996) Gammascintigraphy as a novel method to study the distribution and retention of a bioadhesive vaginal delivery system in sheep. J. Control Rel. 42, 133-142 https://doi.org/10.1016/0168-3659(96)01451-4
  51. Riley RG, Smart JD, Tsibouklis J, Dettmar PW, Hampson F, Davis JA, Kelly G, Wilber RW. (2001) An investigation of mucus/ polymer rheological synergism using synthesized and characterised poly(acrylic acid)s. Int. J. Pharm. 217,87-100 https://doi.org/10.1016/S0378-5173(01)00592-0
  52. Saeed A, Qureshi, Javad S. (2003) Applications of a new device (spindle) for improved characterization of drug release (dissolution) of pharmaceutical products. Eur. J. Pharm. Sci. 19, 291-297 https://doi.org/10.1016/S0928-0987(03)00120-9
  53. Sangekar SA, Vadino WA, Chaudry I, Parr AF, Beilin RM, Digenis GA. (1987) Evaluation of the effect of food and specific gravity of tablets on gastric retention time. Int. J. Pharm. 35, 187-191 https://doi.org/10.1016/0378-5173(87)90129-3
  54. Santos CA, Jacob JS, Hertzog BA, Freedman BD, Press DL Hampichamchai P, Mathiowitz E. (1999) Correlation of two bioadhesion assays: the everted sac technique and the CAHN microbalance. J. Control Rel. 61, 113-122 https://doi.org/10.1016/S0168-3659(99)00109-1
  55. Santus G, Lazzarini C, Bottoni G, Sandefer EP, Page RC, Doll WJ, Ryo UY, Digenis GA. (1997) An in vitro-in vivo investigation of oral bioadhesive controlled release furosemide formulations. Eur. J. Pharm. Biopharm. 44, 39-52 https://doi.org/10.1016/S0939-6411(97)00100-8
  56. Santus GC, Bottoni G, Sala G. (1996) Pharmaceutical controlled release composition with bioadhesive properties. Eur. Patent 516, 141
  57. Slobodanka T, Duncan QM, Craig. (1997) Comparison of different in vitro methods for measuring mucoadhesive performance. Eur. J. Pharm. Biopharm. 44, 159-167 https://doi.org/10.1016/S0939-6411(97)00073-8
  58. SmartJD, Kellaway IW, Worthington HEC. (1984) An in vitro investigation of mucosal adhesive materials for use in controlled drug delivery. J. Pharm. Pharmacol. 36, 295-299
  59. Takka S, Rajbhandari S, Sakr A. (2001) Effect of anionic polymers on the release of propranolol hydrochloride from matrix tablets. J. Pharm. Biopharm. 52,75-82 https://doi.org/10.1016/S0939-6411(01)00147-3
  60. Varshosaz J, Ghafghazi T, Ahme R, Falamarzian M. (2000) Biopharmaceutical characterization of oral theophylline and aminophylline tablets. Quantitative correlation between dissolution and bioavailability studies. Eur. J. Pharm. Biopham. 50, 301-306 https://doi.org/10.1016/S0939-6411(00)00074-6
  61. Walker CV, Wells JI. (1982) Rheological synergism between ionic and non-ionic cellulose gums. Int. J. Pharm. 11, 309-322 https://doi.org/10.1016/0378-5173(82)90081-3
  62. Wilding IR Coupe AJ, Davis SS. (1991) The role of gamma scintigraphy in oral drug delivery. Adv. Drug Deliv. Rev. 7,87-117
  63. Wilson CG, Washington N. (1988) Assessment of disintegration and dissolution of dosage forms in vivo using gamma scintigraphy. Drug Dev. Ind. Pharm. 14, 211-281
  64. Yasunori M, Kanako O, Shigeru Y, Tsuneji N, Kozo T. (2003) Bioavailability of Theophylline and Thiamine Disulfide Incorporated into Mucoadhesive Microspheres Consisting of Dextran Derivatives and Cellulose Acetate Butyrate. Biol. Pharm. Bull. 26, 1744-1747 https://doi.org/10.1248/bpb.26.1744